Actividad biológica in vivo e in vitro de bebidas de cola y sus aditivos

• Autores: Marcos Mateo Fernández
• Directores de la Tesis: Antonio Molina Alcalá (dir. tes.), Ángeles Alonso Moraga (dir. tes.), Sebastián Demyda Peyrás (codir. tes.)
• Lectura: En la Universidad de Córdoba (ESP) ( España ) en 2019
• Idioma: español
• Tribunal Calificador de la Tesis: Rafael Moreno Rojas (presid.), Rafael Font Villa (secret.), María Elena Fernández (voc.)
• Programa de doctorado: Programa de Doctorado en Biociencias y Ciencias Agroalimentarias por la Universidad de Córdoba
• Materias:
  • Ciencias de la vida
    • Genética
• Enlaces
  • Tesis en acceso abierto en: Helvia
• Resumen

  • 1. Introducción o motivación de la tesis Existen factores medioambientales, tales como la dieta, que pueden modificar el riesgo de padecer cáncer y el comportamiento tumoral cambiando la regulación de la expresión génica. Una de las bebidas más consumidas en nuestra dieta a lo largo del mundo es la Coca-Cola y se desarrolló originalmente como un fármaco al igual que la cerveza o el vino y otras bebidas. Sin embargo, también se demostró una relación entre el consumo de estas bebidas y un aumento en la prevalencia de varias enfermedades como la obesidad infantil, diabetes, hipertensión y enfermedades dentales. A pesar de la importancia mundial y la propagación de las bebidas de cola, los estudios científicos que evalúan sus efectos en la salud y el bienestar son bastante escasos y controvertidos. Por lo tanto, se necesitan ensayos para investigar sobre su inocuidad alimentaria y potencial nutracéutico.

    Las pruebas de detección genotoxicológica se han utilizado ampliamente a lo largo del tiempo para evaluar las propiedades saludables de los compuestos antes de ser considerados como sustancias seguras. Hoy en día, la lista de alimentos con propiedades beneficiosas para la salud es interminable, y la evidencia científica que respalda el concepto de ingredientes alimentarios que promueven la salud está en constante crecimiento.

    El objetivo de este trabajo fue evaluar la seguridad biológica y alimentaria de diferentes bebidas a base de cola y sus constituyentes distintivos, agregando a la ciencia, un nuevo cuerpo de datos al aportar más información sobre las propiedades prometedoras de las bebidas de cola.

    2. Contenido de la investigación Con el fin de analizar los efectos de seguridad y protección contra una toxina oxidativa en el organismo in vivo Drosophila, se llevaron a cabo ensayos de toxicidad, antitoxicidad, genotoxicidad, antigenotoxicidad y ensayos de longevidad. Además, el potencial quimiopreventivo y la capacidad de inducir daño en el ADN en las células tumorales (leucemia humana HL-60) se evalúo mediante ensayos in vitro de citotoxicidad, fragmentación del ADN internucleosómica, ensayo del cometa y ensayos de estado de metilación. Todos estos estudios consisten en un conjunto de ensayos de detección biológica donde se pueden verificar varios puntos relacionados con los procesos degenerativos.

    Los resultados obtenidos mostraron que no se encontraron compuestos tóxicos ni genotóxicos para ninguna sustancia probada. La Coca-Cola Clásica, Coca-Cola Sin Cafeína, Coca-Cola Zero, bebidas energéticas, glucosa, ácido fosfórico y ácido cítrico se comportaron como antioxidantes contra el peróxido de hidrógeno. Además, todas las sustancias analizadas y los constituyentes, excepto Coca-Cola Zero y fructosa, mostraron ser antigenotóxicos y ejercen una capacidad protectora contra el peróxido de hidrógeno en el genoma de Drosophila melanogaster. Sin embargo, no se encontraron resultados prometedores en el ensayo longevidad de D. melanogaster. Solo 2 de 8 bebidas liofilizadas (Coca-Cola Clásica y Coca-Cola Light) aumentaron la esperanza de vida de esta mosca. La Coca-Cola Sin Cafeína, Coca-Cola Zero, Pepsi-Cola y RedBull Sin Azúcar (4 de 8 mezclas complejas) redujeron significativamente la longevidad en algunas concentraciones probadas, siendo la Pepsi-Cola y el RedBull Sin Azúcar las peores. En cuanto a los constituyentes, la cafeína, la fructosa, el aspartamo y el ácido cítrico aumentaron la esperanza de vida en cierta medida y solo el ácido fosfórico la disminuyó. Todas las bebidas liofilizadas y los compuestos simples fueron citotóxicos en la línea celular HL-60, excepto la cafeína, el ciclamato y la taurina. La segunda concentración más alta ensayada de Coca-Cola Clásica, fructosa y RedBull Clásico indujo la fragmentación del ADN en la línea celular HL-60. Sin embargo, a pesar de que todos los compuestos y bebidas ensayadas indujeron daño en el ADN a nivel celular (excepto el ácido cítrico, el caramelo tipo IV, la Pepsi-Cola y el RedBull Sin Azúcar) ninguno de ellos produjo valores de TM apoptóticos llevando a cabo el ensayo del cometa. Por lo tanto, la muerte celular mostrada por la mayoría de las bebidas liofilizadas y los compuestos biológicos no se produce por vía apoptótica, sino que se debe a la actividad necrótica según el ensayo del cometa. Teniendo en cuenta el estado de hipermetilación como marcador de estabilidad genómica en la línea de cáncer HL-60, la Coca-Cola Light, Coca-Cola Zero y Coca-Cola Light Sin Cafeína produjo un aumento en el nivel de metilación en cada concentración probada. Al menos, una concentración de Coca-Cola Clásica, Coca-Cola Sin Cafeína, Pepsi-Cola y RedBull Sin Azúcar hipermetiló los transposones ensayados en la línea celular HL-60. El acesulfamo potásico y el ácido fosfórico aumentaron el nivel de metilación en cada concentración. El estado de metilación de la línea celular HL-60 disminuyó cuando se trataron con ciclamato, ácido cítrico, color caramelo IV y RedBull Clásico en al menos una concentración probada y ninguna de las concentraciones probadas las hipermetiló.

    En cuanto a los resultados del enfoque cuantitativo, el acesulfamo y el color caramelo IV podrían ser los compuestos responsables de los bajos puntajes obtenidos en Pepsi-Cola y bebidas dietéticas, especialmente en Coca-Cola Light Sin Cafeína. La puntación obtenida en RedBull Clásica, RedBull Sin Azúcar y la taurina fue la misma, por lo que la taurina puede tener una influencia en RedBull Clásico y RedBull Sin Azúcar y los otros compuestos podrían camuflarse entre sí con un efecto sinérgico.

    3. Conclusión En resumen, las bebidas de cola liofilizadas y las bebidas energéticas demostraron ser seguras para D. melanogaster. Se necesitan más estudios para dilucidar las actividades biológicas y el potencial nutracéutico de las bebidas de cola para resolver la información controvertida que se encuentra en las bases de datos científicas debido a los resultados prometedores obtenidos en moscas y en la línea celular HL-60. Por ejemplo, se deben usar células no tumorales para compararlas con nuestros estudios in vitro. Ensayos clínicos en humanos también se podrían realizar usando los compuestos apropiados.

    4. Bibliografía Abhilash, M., M. S. Paul, M. V. Varghese and R. H. Nair, 2011 Effect of long term intake of aspartame on antioxidant defense status in liver. Food and chemical toxicology 49: 1203-1207.

    Abraham, S. K., and S. P. Singh, 1999 Anti-genotoxicity and glutathione S-transferase activity in mice pretreated with caffeinated and decaffeinated coffee. Food Chem Toxicol 37: 733-739.

    Ahmad, M. K., A. A. Khan, S. N. Ali and R. Mahmood, 2015 Chemoprotective effect of taurine on potassium bromate-induced DNA damage, DNA-protein cross-linking and oxidative stress in rat intestine. PloS one 10: e0119137.

    Ahmed, F. E., and D. B. Thomas, 1992 Assessment of the carcinogenicity of the nonnutritive sweetener cyclamate. Critical reviews in toxicology 22: 81-118.

    Al-Ani, F. Y., and S. K. Al-Lami, 1988 Absence of mutagenic activity of acidity regulators in the Ames Salmonella/microsome test. Mutation Research/Genetic Toxicology 206: 467-470.

    AlSuhaibani, E. S., 2010 In vivo cytogenetic studies on aspartame. Comparative and functional genomics 2010.

    Alsunni, A. A., 2015 Energy Drink Consumption: Beneficial and Adverse Health Effects. International journal of health sciences 9: 468.

    Anazetti, M. C., P. S. Melo, N. Duran and M. Haun, 2003 Comparative cytotoxicity of dimethylamide-crotonin in the promyelocytic leukemia cell line (HL60) and human peripheral blood mononuclear cells. Toxicology 188: 261-274.

    Andrew, L. E., 1959 The Mutagenic Activity of Caffein in Drosophila. The American Naturalist 93: 135-138.

    Antequera, F., and A. Bird, 1993 Number of CpG islands and genes in human and mouse. Proceedings of the National Academy of Sciences 90: 11995-11999.

    Anter, J., S. Demyda-Peyras, M. P. Delgado-Torre, J. Campos-Sanchez, M. D. Luque De Castro et al., 2015 Biological and health promoting activity of vinification byproducts produced in Spanish vineyards. South African Journal of Enology and Viticulture 36: 126-133.

    Anter, J., Z. Fernandez-Bedmar, M. Villatoro-Pulido, S. Demyda-Peyras, M. Moreno-Millan et al., 2011 A pilot study on the DNA-protective, cytotoxic, and apoptosis-inducing properties of olive-leaf extracts. Mutat Res 723: 165-170.

    Anter, J., I. Tasset, S. Demyda-Peyrás, I. Ranchal, M. Moreno-Millán et al., 2014 Evaluation of potential antigenotoxic, cytotoxic and proapoptotic effects of the olive oil by-product "alperujo", hydroxytyrosol, tyrosol and verbascoside. Mutation Research - Genetic Toxicology and Environmental Mutagenesis 772: 25-33.

    Ariza, R. R., G. Dorado, M. Barbancho and C. Pueyo, 1988 Study of the causes of direct-acting mutagenicity in coffee and tea using the Ara test in Salmonella typhimurium. Mutat Res 201: 89-96.

    Aruoma, O., B. Halliwell, B. M. Hoey and J. Butler, 1988 The antioxidant action of taurine, hypotaurine and their metabolic precursors. Biochemical Journal 256: 251-255.

    Ashok, I., D. Wankhar, R. Sheeladevi and W. Wankhar, 2014 Long-term effect of aspartame on the liver antioxidant status and histopathology in Wistar albino rats. Biomedicine & Preventive Nutrition 4: 299-305.

    Aslam, H. M., A. Mughal, M. M. Edhi, S. Saleem, M. H. Rao et al., 2013 Assessment of pattern for consumption and awareness regarding energy drinks among medical students. Archives of Public Health 71: 31.

    Bandyopadhyay, A., S. Ghoshal and A. Mukherjee, 2008a Genotoxicity testing of low-calorie sweeteners: aspartame, acesulfame-K, and saccharin. Drug and chemical toxicology 31: 447-457.

    Bandyopadhyay, D., P. K. Dutta, S. G. Dastidar and T. K. Chatterjee, 2008b In vitro and in vivo antidiarrhoeal activity of epigallocatechin 3-gallate: a major catechin isolated from indian green tea. Oriental Pharmacy and Experimental Medicine 8: 171-177.

    Barzegar, A., and A. A. Moosavi-Movahedi, 2011 Intracellular ROS protection efficiency and free radical-scavenging activity of curcumin. PLoS One 6: e26012.

    Batista, C., L. Barros, A. M. Carvalho and I. C. Ferreira, 2011 Nutritional and nutraceutical potential of rape (Brassica napus L. var. napus) and “tronchuda” cabbage (Brassica oleraceae L. var. costata) inflorescences. Food and chemical toxicology 49: 1208-1214.

    Baumgartner-Parzer, S. M., L. Wagner, M. Pettermann, J. Grillari, A. Gessl et al., 1995 High-glucose–triggered apoptosis in cultured endothelial cells. Diabetes 44: 1323-1327.

    Beckingham, K. M., J. D. Armstrong, M. J. Texada, R. Munjaal and D. A. Baker, 2007 Drosophila melanogaster-the model organism of choice for the complex biology of multi-cellular organisms. Gravitational and Space Research 18.

    Bell, R., A. Hubbard, R. Chettier, D. Chen, J. P. Miller et al., 2009 A human protein interaction network shows conservation of aging processes between human and invertebrate species. PLoS Genet 5: e1000414.

    Bellisle, F., and A. Drewnowski, 2007 Intense sweeteners, energy intake and the control of body weight. European journal of clinical nutrition 61: 691.

    Bier, E., 2005 Drosophila, the golden bug, emerges as a tool for human genetics. Nature Reviews Genetics 6: 9-23.

    Bigard, A., 2010 [Risks of energy drinks in youths]. Archives de pediatrie: organe officiel de la Societe francaise de pediatrie 17: 1625-1631.

    Boissinot, S., A. Entezam and A. V. Furano, 2001 Selection against deleterious LINE-1-containing loci in the human lineage. Molecular biology and evolution 18: 926-935.

    Bopp, B. A., R. C. Sonders, J. W. Kesterson and A. Renwick, 1986 Toxicological aspects of cyclamate and cyclohexylamine. CRC critical reviews in toxicology 16: 213-306.

    Bouckenooghe, T., C. Remacle and B. Reusens, 2006 Is taurine a functional nutrient? Current Opinion in Clinical Nutrition & Metabolic Care 9: 728-733.

    Branen, A. L., P. M. Davidson, S. Salminen and J. Thorngate, 2001 Food additives. CRC Press.

    Brantom, P. G., I. F. Gaunt and P. Grasso, 1973 Long-term toxicity of sodium cyclamate in mice. Food and Cosmetics Toxicology 11: 735-746.

    Breitman, T. R., 1990 Growth and differentiation of human myeloid-leukemia cell-line HL-60. Methods in Enzymology 190: 118-130.

    Brima, E., and A. Abbas, 2014 Determination of Citric acid in Soft drinks, Juice drinks and Energy drinks using Titration. Int J Chem Stud 1: 30-34.

    Bross, T. G., B. Rogina and S. L. Helfand, 2005 Behavioral, physical, and demographic changes in Drosophila populations through dietary restriction. Aging cell 4: 309-317.

    Brusick, D., M. Cifone, R. Young and S. Benson, 1989 Assessment of the genotoxicity of calcium cyclamate and cyclohexylamine. Environmental and molecular mutagenesis 14: 188-199.

    Brusick, D., D. Jagannath, S. Galloway and E. Nestmann, 1992 Genotoxicity hazard assessment of Caramel Colours III and IV. Food and chemical toxicology 30: 403-410.

    Busserolles, J. r. m., E. Gueux, E. Rock, C. Demigne, A. Mazur et al., 2003 Oligofructose protects against the hypertriglyceridemic and pro-oxidative effects of a high fructose diet in rats. The Journal of nutrition 133: 1903-1908.

    Butchko, H. H., W. W. Stargel, C. P. Comer, D. A. Mayhew, C. Benninger et al., 2002 Aspartame: review of safety. Regulatory Toxicology and Pharmacology 35: S1-S93.

    Cao, X., L. Fang, S. Gibbs, Y. Huang, Z. Dai et al., 2007 Glucose uptake inhibitor sensitizes cancer cells to daunorubicin and overcomes drug resistance in hypoxia. Cancer chemotherapy and pharmacology 59: 495-505.

    Carocho, M., M. F. Barreiro, P. Morales and I. C. Ferreira, 2014 Adding molecules to food, pros and cons: A review on synthetic and natural food additives. Comprehensive Reviews in Food Science and Food Safety 13: 377-399.

    Carocho, M., and I. C. Ferreira, 2013 A review on antioxidants, prooxidants and related controversy: natural and synthetic compounds, screening and analysis methodologies and future perspectives. Food and chemical toxicology 51: 15-25.

    Cavka, A., M. Stupin, A. Panduric, A. Plazibat, A. Cosic et al., 2015 Adrenergic System Activation Mediates Changes in Cardiovascular and Psychomotoric Reactions in Young Individuals after Red Bull© Energy Drink Consumption. International journal of endocrinology.

    Celec, P., and M. Behuliak, 2010 Behavioural and endocrine effects of chronic cola intake. Journal of Psychopharmacology 24: 1569-1572.

    Ceriello, A., P. dello Russo, P. Amstad and P. Cerutti, 1996 High glucose induces antioxidant enzymes in human endothelial cells in culture: evidence linking hyperglycemia and oxidative stress. Diabetes 45: 471-477.

    Cillo, F., 2011 0% Calorias,% Azúcares. Un análisis sobre las bebidas Light del mercado. La tendencia a endulzar naturalmente: Stevia. ISDe Sports Magazine 3.

    Ciszewicz, M., A. PoLubinska, A. Antoniewicz, K. Suminska-Jasinska and A. BrĘborowicz, 2009 Sulodexide suppresses inflammation in human endothelial cells and prevents glucose cytotoxicity. Translational Research 153: 118-123.

    Collins, A. R., 2004 The comet assay for DNA damage and repair: principles, applications, and limitations. Mol Biotechnol 26: 249-261.

    Collins, S. J., 1987 The HL-60 promyelocytic leukemia cell line: proliferation, differentiation, and cellular oncogene expression. Blood 70: 1233-1244.

    Collins, S. J., R. C. Gallo and R. E. Gallagher, 1977 Continuous growth and differentiation of human myeloid leukaemic cells in suspension culture. Nature 270: 347-349.

    Combeau, S., M. Chatelut and O. Vittori, 2002 Identification and simultaneous determination of Azorubin, Allura red and Ponceau 4R by differential pulse polarography: application to soft drinks. Talanta 56: 115-122.

    Consortium, I. H. G. S., 2001 Initial sequencing and analysis of the human genome. Nature 409: 860.

    Cordoba-Canero, D., V. Cognat, R. R. Ariza, T. Roldan Arjona and J. Molinier, 2017 Dual control of ROS1-mediated active DNA demethylation by DNA damage-binding protein 2 (DDB2). Plant J 92: 1170-1181.

    Cozzi, R., R. Ricordy, F. Bartolini, L. Ramadori, P. Perticone et al., 1995 Taurine and ellagic acid: Two differently‐acting natural antioxidants. Environmental and molecular mutagenesis 26: 248-254.

    Creppy, E. E., I. Baudrimont and A. MARIE, 1998 How aspartame prevents the toxicity of ochratoxin A. The Journal of toxicological sciences 23: 165-172.

    Cruzan, G., 2009 Assessment of the cancer potential of methanol. Critical reviews in toxicology 39: 347-363.

    Cunha, S., A. Barrado, M. Faria and J. Fernandes, 2011 Assessment of 4-(5-) methylimidazole in soft drinks and dark beer. Journal of Food Composition and Analysis 24: 609-614.

    Cuomo, R., G. Sarnelli, M. F. Savarese and M. Buyckx, 2009 Carbonated beverages and gastrointestinal system: between myth and reality. Nutr Metab Cardiovasc Dis 19: 683-689.

    Chan, R. I. M., H. F. Stich, M. P. Rosin and W. D. Powrie, 1982 Antimutagenic activity of browning reaction products. Cancer Letters 15: 27-33.

    Chang, D. J., G. M. Ringold and R. A. Heller, 1992 Cell killing and induction of manganous superoxide dismutase by tumor necrosis factor-(α is mediated by lipoxygenase metabolites of arachidonic acid. Biochemical and biophysical research communications 188: 538-546.

    Chen, Y.-X., X.-R. Zhang, W.-F. Xie and S. Li, 2004 Effects of taurine on proliferation and apoptosis of hepatic stellate cells in vitro. Hepatobiliary Pancreat Dis Int 3: 106-109.

    Cheng, L. Y., L. M. Parsons and H. E. Richardson, 2013 Modelling Cancer in Drosophila: The Next Generation. eLS.

    Choudhary, A. K., and R. S. Devi, 2015 Longer period of oral administration of aspartame on cytokine response in Wistar albino rats. Endocrinología y Nutrición (English Edition) 62: 114-122.

    Chung, Y.-S., and M. Lee, 2013 Genotoxicity assessment of erythritol by using short-term assay. Toxicological research 29: 249.

    D’Angelo, G., A. A. Elmarakby, D. M. Pollock and D. W. Stepp, 2005 Fructose feeding increases insulin resistance but not blood pressure in Sprague-Dawley rats. Hypertension 46: 806-811.

    Dalderup, L., and W. Visser, 1971 Influence of extra sucrose, fats, protein and of cyclamate in the daily food on the life-span of rats. Experientia 27: 519-521.

    Dang, T. S., M. Walker, D. Ford and R. A. Valentine, 2014 Nutrigenomics: the role of nutrients in gene expression. Periodontology 2000 64: 154-160.

    De Koning, L., V. S. Malik, M. D. Kellogg, E. B. Rimm, W. C. Willett et al., 2012 Sweetened beverage consumption, incident coronary heart disease and biomarkers of risk in men. Circulation: CIRCULATIONAHA. 111.067017.

    Delgado-Vargas, F., and O. Paredes-López, 2002 Natural colorants for food and nutraceutical uses. CRC press.

    Demir, E., F. Turna, S. Aksakal, B. Kaya and R. Marcos, 2014 Genotoxicity of different sweeteners in Drosophila. Fresenius Environmental Bulletin 23: 3427-3433.

    Deshpande, S. A., G. B. Carvalho, A. Amador, A. M. Phillips, S. Hoxha et al., 2014 Quantifying Drosophila food intake: comparative analysis of current methodology. Nature methods 11: 535-540.

    Devlin, H., M. A. Bassiouny and D. Boston, 2006 Hardness of enamel exposed to Coca-Cola and artificial saliva. Journal of oral rehabilitation 33: 26-30.

    Driver, C. J., and G. Cosopodiotis, 1979 The effect of dietary fat on longevity of Drosophila melanogaster. Experimental gerontology 14: 95-100.

    Durnev, A. D., A. V. Oreshchenko, A. V. Kulakova, N. F. Beresten and S. B. Seredenin, 1995 Clastogenic activity of dietary sugar substitutes. Vopr Med Khim 41: 31-33.

    Düsman, E., A. P. Berti, L. C. Soares and V. E. P. Vicentini, 2013 Cytotoxicity and mutagenicity of cola and grape flavored soft drinks in bone marrow cells of rodents. Food Science and Technology 33: 122-126.

    EFSA, European Food Safety Authority. http://www.efsa.europa.eu/ Egger, G., G. Liang, A. Aparicio and P. A. Jones, 2004 Epigenetics in human disease and prospects for epigenetic therapy. Nature 429: 457.

    Ekmekcioglu, C., G. Strauss-Blasche, V. J. Leibetseder and W. Marktl, 1999 Toxicological and biochemical effects of different beverages on human intestinal cells. Food Research International 32: 421-427.

    El-Osta, A., D. Brasacchio, D. Yao, A. Pocai, P. L. Jones et al., 2008 Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia. The Journal of experimental medicine 205: 2409-2417.

    El‑Terras, A., M. M. Soliman, A. Alkhedaide, H. F. Attia, A. Alharthy et al., 2016 Carbonated soft drinks induce oxidative stress and alter the expression of certain genes in the brains of Wistar rats. Molecular medicine reports 13: 3147-3154.

    Elfatah, A. A. A., I. S. Ghaly and S. M. Hanafy, 2012 Cytotoxic effect of aspartame (diet sweet) on the histological and genetic structures of female albino rats and their offspring. Pakistan Journal of Biological Sciences 15: 904.

    Eluwa, M., I. Inyangmme, A. Akpantah, T. Ekanem, M. Ekong et al., 2013 A comparative study of the effect of diet and soda carbonated drinks on the histology of the cerebellum of adult female albino Wistar rats. African health sciences 13: 541-545.

    Ergun, M. A., Y. Soysal, E. Kismet, C. Akay, R. Dundaroz et al., 2006 Investigating the in vitro effect of taurine on the infant lymphocytes by sister chromatid exchange. Pediatrics international 48: 284-286.

    Fabiani, R., P. Rosignoli, A. De Bartolomeo, R. Fuccelli and G. Morozzi, 2012 Genotoxicity of alkene epoxides in human peripheral blood mononuclear cells and HL60 leukaemia cells evaluated with the comet assay. Mutat Res 747: 1-6.

    Fahrig, R., 1992 Tests for recombinagens in mammals in vivo. Mutat Res 284: 177-183.

    Fairbairn, D. W., and K. L. O’Neill, 1995 Necrotic DNA degradation mimics apoptotic nucleosomal fragmentation comet tail length. In Vitro Cellular & Developmental Biology-Animal 31: 171-173.

    Fairweather, F. A., and C. A. Swann, 1981 Food additives and cancer. Proceedings of the Nutrition Society 40: 21-30.

    Farhan, E. M., and R. F. Tawfiq, 2016 Detection of Cytotoxicity and Carcinogenicity of Soft Drink" Cola" on Allium Cepa Root Cells.

    FDA, U. S. Food and Drug Administration. https://www.fda.gov/ Feinberg, A. P., 2008 Epigenetics at the epicenter of modern medicine. Jama 299: 1345-1350.

    Feng, C., S. Wong, Q. Dong, J. Bruce, R. Mehta et al., 2009 Hepatocyte inflammation model for cytotoxicity research: fructose or glycolaldehyde as a source of endogenous toxins. Archives of physiology and biochemistry 115: 105-111.

    Fernandez-Bedmar, Z., J. Anter, S. de La Cruz-Ares, A. Munoz-Serrano, A. Alonso-Moraga et al., 2011 Role of citrus juices and distinctive components in the modulation of degenerative processes: genotoxicity, antigenotoxicity, cytotoxicity, and longevity in Drosophila. J Toxicol Environ Health A 74: 1052-1066.

    Fesus, L., Z. Szondy and I. Uray, 1995 Probing the molecular program of apoptosis by cancer chemopreventive agents. J Cell Biochem Suppl 22: 151-161.

    Findikli, Z., and S. Turkoglu, 2014 Determination of the effects of some artificial sweeteners on human peripheral lymphocytes using the comet assay. Journal of Toxicology and Environmental Health Sciences 6: 147-153.

    Fleming, J. E., I. Reveillaud and A. Niedzwiecki, 1992 Role of oxidative stress in Drosophila aging. Mutat Res 275: 267-279.

    Fletcher, J. M., D. Frisvold and N. Tefft, 2008 Can Soft Drink Taxes Reduce Population Weight? Emory Economics.

    Forchhammer, L., C. Ersson, S. Loft, L. Möller, R. W. Godschalk et al., 2012 Inter-laboratory variation in DNA damage using a standard comet assay protocol. Mutagenesis 27: 665-672.

    Fortini, M. E., M. P. Skupski, M. S. Boguski and I. K. Hariharan, 2000 A survey of human disease gene counterparts in the Drosophila genome. The Journal of cell biology 150: F23-F30.

    Franconi, F., A. Loizzo, G. Ghirlanda and G. Seghieri, 2006 Taurine supplementation and diabetes mellitus. Current Opinion in Clinical Nutrition & Metabolic Care 9: 32-36.

    Frei, H., and F. E. Wurgler, 1988 Statistical methods to decide whether mutagenicity test data from Drosophila assays indicate a positive, negative, or inconclusive result. Mutat Res 203: 297-308.

    Frei, H., and F. E. Wurgler, 1995 Optimal experimental design and sample size for the statistical evaluation of data from somatic mutation and recombination tests (SMART) in Drosophila. Mutat Res 334: 247-258.

    Frenzel, J., J. Richter and K. Eschrich, 2002 Fructose inhibits apoptosis induced by reoxygenation in rat hepatocytes by decreasing reactive oxygen species via stabilization of the glutathione pool. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research 1542: 82-94.

    Fry, J. D., and M. Saweikis, 2006 Aldehyde dehydrogenase is essential for both adult and larval ethanol resistance in Drosophila melanogaster. Genetics Research 87: 87-92.

    Gaido, M. L., and J. A. Cidlowski, 1991 Identification, purification, and characterization of a calcium-dependent endonuclease (NUC18) from apoptotic rat thymocytes. NUC18 is not histone H2B. J Biol Chem 266: 18580-18585.

    Gallagher, R., S. Collins, J. Trujillo, K. McCredie, M. Ahearn et al., 1979 Characterization of the continuous, differentiating myeloid cell line (HL-60) from a patient with acute promyelocytic leukemia. Blood 54: 713-733.

    Gallay, A., F. Van Loock, S. Demarest, J. Van Der Heyden, B. Jans et al., 2002 Belgian Coca-Cola-related outbreak: Intoxication, mass sociogenic illness, or both? American Journal of Epidemiology 155: 140-147.

    Giammattei, J., G. Blix, H. H. Marshak, A. O. Wollitzer and D. J. Pettitt, 2003 Television Watching and Soft Drink ConsumptionAssociations With Obesity in 11- to 13-Year-Old Schoolchildren. Archives of Pediatrics & Adolescent Medicine 157: 882-886.

    Giorgio, M., M. Trinei, E. Migliaccio and P. G. Pelicci, 2007 Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals? Nat Rev Mol Cell Biol 8: 722-728.

    Gold, E. B., L. Gordis, M. D. Diener, R. Seltser, J. K. Boitnott et al., 1985 Diet and other risk factors for cancer of the pancreas. Cancer 55: 460-467.

    Golembiowska, K., A. Dziubina, M. Kowalska and K. Kaminska, 2009 Effect of adenosine A(2A) receptor antagonists on L-DOPA-induced hydroxyl radical formation in rat striatum. Neurotox Res 15: 155-166.

    Gomez, I., 2015 The Effect of Aspartame & Sodium Nitrite on Drosophila melanogaster, pp. AAAS Anual Meeting. AJAS Medicine.

    Gonzalez, C., 2013 Drosophila melanogaster: a model and a tool to investigate malignancy and identify new therapeutics. Nature Reviews Cancer 13: 172-183.

    Graf, U., S. K. Abraham, J. Guzman-Rincon and F. E. Wurgler, 1998 Antigenotoxicity studies in Drosophila melanogaster. Mutat Res 402: 203-209.

    Graf, U., and F. E. Wurgler, 1986 Investigation of coffee in Drosophila genotoxicity tests. Food Chem Toxicol 24: 835-842.

    Graf, U., F. E. Wurgler, A. J. Katz, H. Frei, H. Juon et al., 1984 Somatic mutation and recombination test in Drosophila melanogaster. Environ Mutagen 6: 153-188.

    Grover, D., P. P. Majumder, C. B. Rao, S. K. Brahmachari and M. Mukerji, 2003 Nonrandom distribution of alu elements in genes of various functional categories: insight from analysis of human chromosomes 21 and 22. Molecular biology and evolution 20: 1420-1424.

    Gürbüzel, M., H. Uysal and H. Kızılet, 2015 Assessment of genotoxic potential of two mycotoxins in the wing spot test of Drosophila melanogaster. Toxicology and industrial health 31: 261-267.

    Gyori, B. M., G. Venkatachalam, P. S. Thiagarajan, D. Hsu and M. V. Clement, 2014 OpenComet: An automated tool for comet assay image analysis. Redox Biology 2: 457-465.

    Halas, M., M. Izdebska, A. Klimaszewska-Wisniewska, M. Gagat, D. Radciniewska et al., 2014 Caffeine induces cytoskeletal changes and cell death in H1299 cells. Central European Journal of Biology 9: 727-738.

    Hannah, C., E. Priya and A. Mammen, 2010 Duration dependent mutagenic study of cola drinks on Allium cepa L. Biosciences, Biotechnology Research Asia 7: 807-812.

    Hansen, M., D. Baunsgaard, H. Autrup, U. B. Vogel, P. Møller et al., 2008 Sucrose, glucose and fructose have similar genotoxicity in the rat colon and affect the metabolome. Food and chemical toxicology 46: 752-760.

    Hargreaves, M. B., B. C. Jones, D. A. Smith and A. Gescher, 1994 Inhibition of p-nitrophenol hydroxylase in rat liver microsomes by small aromatic and heterocyclic molecules. Drug Metabolism and Disposition 22: 806-810.

    Hartmann, A., E. Kiskinis, A. Fjällman and W. Suter, 2001 Influence of cytotoxicity and compound precipitation on test results in the alkaline comet assay. Mutation Research - Genetic Toxicology and Environmental Mutagenesis 497: 199-212.

    Hastings, P. J., 1992 Mechanism and control of recombination in fungi. Mutat Res 284: 97-110.

    Heidari, R., H. Babaei and M. A. Eghbal, 2013 Cytoprotective effects of taurine against toxicity induced by isoniazid and hydrazine in isolated rat hepatocytes. Archives of Industrial Hygiene and Toxicology 64: 201-210.

    Higgins, J. P., T. D. Tuttle and C. L. Higgins, 2010 Energy beverages: content and safety, pp. 1033-1041 in Mayo Clinic Proceedings. Elsevier.

    Hininger-Favier, I., R. Benaraba, S. Coves, R. A. Anderson and A.-M. Roussel, 2009 Green tea extract decreases oxidative stress and improves insulin sensitivity in an animal model of insulin resistance, the fructose-fed rat. Journal of the American College of Nutrition 28: 355-361.

    Hisae, O., O. Shinshi and H. Kogo, 1982 Toxicity of several phosphoric acid esters in rats. Toxicology Letters 13: 29-34.

    Hoffmann, G. R., 1992 Bacterial assays for recombinagens. Mutat Res 284: 125-146.

    Hong, M. Y., L. Mansour, D. S. Klarich, L. Copp and K. Bloem, 2016 Comparison of antioxidant capacity of commonly consumed youth beverages in the United States. International Journal of Food Science & Technology 51: 1409-1416.

    Hong, W. K., and M. B. Sporn, 1997 Recent advances in chemoprevention of cancer. Science 278: 1073-1077.

    Horio, Y., Y. Sun, C. Liu, T. Saito and M. Kurasaki, 2014 Aspartame-induced apoptosis in PC12 cells. Environmental toxicology and pharmacology 37: 158-165.

    Huang, D., 2011 The Effect of Acesulfame Potassium on Phosphoinositide 3-Kinase-Induced Viability and Lifespan in Drosophila melanogaster. Acesulfame Potassium and Drosophila melanogaster: 1-26.

    Hwang, I.-s., H. Ho, B. B. Hoffman and G. M. Reaven, 1987 Fructose-induced insulin resistance and hypertension in rats. Hypertension 10: 512-516.

    Ibiebele, T. I., M. C. Hughes, P. O'Rourke, P. M. Webb and D. C. Whiteman, 2008 Cancers of the esophagus and carbonated beverage consumption: a population-based case-control study. Cancer Causes Control 19: 577-584.

    Idaomar, M., R. El Hamss, F. Bakkali, N. Mezzoug, A. Zhiri et al., 2002 Genotoxicity and antigenotoxicity of some essential oils evaluated by wing spot test of Drosophila melanogaster. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 513: 61-68.

    Ishida, Y., Y. Furukawa, J. A. Decaprio, M. Saito and J. D. Griffin, 1992 Treatment of myeloid leukemic cells with the phosphatase inhibitor okadaic acid induces cell cycle arrest at either G1/S or G2/M depending on dose. J Cell Physiol 150: 484-492.

    Ishidate Jr, M., T. Sofuni, K. Yoshikawa, M. Hayashi, T. Nohmi et al., 1984 Primary mutagenicity screening of food additives currently used in Japan. Food and Chemical Toxicology 22: 623-636.

    Ishii, N., Z. Ogawa, K. Suzuki, K. Numakami, T. Saruta et al., 1996 Glucose loading induces DNA fragmentation in rat proximal tubular cells. Metabolism 45: 1348-1353.

    Ito, T., N. Yoshikawa, T. Inui, N. Miyazaki, S. W. Schaffer et al., 2014 Tissue depletion of taurine accelerates skeletal muscle senescence and leads to early death in mice. PloS one 9: e107409.

    Itoyama, M. M., H. E. M. De Campos Bicudo and A. J. Manzato, 1998 The development of resistance to caffeine in Drosophila prosaltans: Productivity and longevity after ten generations of treatment. Cytobios 1998: 81-93.

    Ja, W. W., G. B. Carvalho, E. M. Mak, N. N. de la Rosa, A. Y. Fang et al., 2007 Prandiology of Drosophila and the CAFE assay. Proc Natl Acad Sci U S A 104: 8253-8256.

    Jacobson, M. F., and K. D. Brownell, 2000 Small taxes on soft drinks and snack foods to promote health. American Journal of Public Health 90: 854.

    Jafari, M., and A. Rabbani, 2000 Dose and time dependent effects of caffeine on superoxide release, cell survival and DNA fragmentation of alveolar macrophages from rat lung. Toxicology 149: 101-108.

    James, J., and D. Kerr, 2005 Prevention of childhood obesity by reducing soft drinks. International journal of obesity 29: S54-S57.

    James, J. E., 2004 Critical review of dietary caffeine and blood pressure: a relationship that should be taken more seriously. Psychosom Med 66: 63-71.

    Jeffrey, A. M., and G. M. Williams, 2000 Lack of DNA-damaging activity of five non-nutritive sweeteners in the rat hepatocyte/DNA repair assay. Food and Chemical Toxicology 38: 335-338.

    Jeon, S.-H., M.-Y. Lee, S.-J. Kim, S.-G. Joe, G.-B. Kim et al., 2007 Taurine increases cell proliferation and generates an increase in [Mg2+] i accompanied by ERK 1/2 activation in human osteoblast cells. FEBS letters 581: 5929-5934.

    Jing, Q., S.-M. Xin, Z.-J. Cheng, W.-B. Zhang, R. Zhang et al., 1999 Activation of p38 Mitogen-Activated Protein Kinase by Oxidized LDL in Vascular Smooth Muscle Cells Mediation via Pertussis Toxin–Sensitive G Proteins and Association With Oxidized LDL-Induced Cytotoxicity. Circulation research 84: 831-839.

    Jirtle, R. L., and M. K. Skinner, 2007 Environmental epigenomics and disease susceptibility. Nat Rev Genet 8: 253-262.

    Jung, R., and H. Hollander, 1986 Sunett, Study of the mutagenic potential in strains of Salmonella typhimurium (Ames test) and Escherichia coli. Pharma Research Toxicology, Hoechst AG, Bericht.

    Jung, R., and R. Kreiling, 1991 Acesulfame K. Edited by Mayer and Kemper, pp. Marcel Dekker, New York.

    Kamath, S., K. Vijaynarayana, D. P. Shetty and P. Shetty, 2010 Evaluation of genotoxic potential of aspartame. Pharmacologyonline 1: 753-769.

    Kammerer, M., J. A. Jaramillo, A. García, J. C. Calderín and L. H. Valbuena, 2014 Effects of energy drink major bioactive compounds on the performance of young adults in fitness and cognitive tests: a randomized controlled trial. Journal of the international society of sports nutrition 11: 1-7.

    Kang, Y., H.-S. Lee, N.-J. Paik, W.-S. Kim and M. Yang, 2010 Evaluation of enteral formulas for nutrition, health, and quality of life among stroke patients. Nutrition research and practice 4: 393-399.

    Kapicioglu, S., A. Baki, Y. Tekelioglu, M. Arslan, M. Sari et al., 1998 The inhibiting effect of cola on gastric mucosal cell cycle proliferation in humans. Scand J Gastroenterol 33: 701-703.

    Karstadt, M., 2010 Inadequate toxicity tests of food additive acesulfame. International journal of occupational and environmental health 16: 89-96.

    Karunakaran, U., and K.-G. Park, 2013 A systematic review of oxidative stress and safety of antioxidants in diabetes: focus on islets and their defense. Diabetes & metabolism journal 37: 106-112.

    Kashanian, S., M. M. Khodaei and F. Kheirdoosh, 2013 In vitro DNA binding studies of aspartame, an artificial sweetener. Journal of Photochemistry and Photobiology B: Biology 120: 104-110.

    Katsue, H., Y. Higashi, N. Baba, M. Aoki, M. Sakanoue et al., 2014 Allergic reaction caused by acesulfame potassium in foods. Contact dermatitis 71: 251-252.

    Kenyon, C., 2005 The plasticity of aging: insights from long-lived mutants. Cell 120: 449-460.

    Kesava, R. C., T. Sivapriya, K. U. Arun and C. Ramalingam, 2016 Optimization of food acidulant to enhance the organoleptic property in fruit jellies. Journal of Food Processing and Technology 7: 635.

    Kim, H. M., C.-H. Do and D. H. Lee, 2010 Taurine reduces ER stress in C. elegans. J Biomed Sci 17: S26.

    Kitts, D. D., C. Wu, A. Kopec and T. Nagasawa, 2006 Chemistry and genotoxicity of caramelized sucrose. Molecular nutrition & food research 50: 1180-1190.

    Knaap, A. G. A. C., P. G. N. Kramers and F. H. Sobels, 1973 Lack of mutagenicity of the cyclamate metabolites in Drosophila. Mutation Research/Environmental Mutagenesis and Related Subjects 21: 341-344.

    Köller, M., P. Wachtler, A. Dávid, G. Muhr and W. König, 1997 Arachidonic Acid Induces DNA-Fragmentation in Human Polymorphonuclear Neutrophil Granulocytes. Inflammation 21: 463-474.

    Ladas, S. D., D. Kamberoglou, G. Karamanolis, J. Vlachogiannakos and I. Zouboulis-Vafiadis, 2013 Systematic review: Coca-Cola can effectively dissolve gastric phytobezoars as a first-line treatment. Aliment Pharmacol Ther 37: 169-173.

    Lander, E. S., L. M. Linton, B. Birren, C. Nusbaum, M. C. Zody et al., 2001 Initial sequencing and analysis of the human genome. Nature 409: 860-921.

    Lange, F. T., M. Scheurer and H.-J. Brauch, 2012 Artificial sweeteners—a recently recognized class of emerging environmental contaminants: a review. Analytical and bioanalytical chemistry 403: 2503-2518.

    Laude, E. A., K. S. Higgins and A. H. Morice, 1993 A Comparative Study of the Effects of Citric Acid, Capsaicin and Resiniferatoxin on the Cough Challenge in Guinea-pig and Man. Pulmonary Pharmacology 6: 171-175.

    Lee, C., 2000 Antioxidant ability of caffeine and its metabolites based on the study of oxygen radical absorbing capacity and inhibition of LDL peroxidation. Clin Chim Acta 295: 141-154.

    Lee, K. P., S. J. Simpson, F. J. Clissold, R. Brooks, J. W. O. Ballard et al., 2008 Lifespan and reproduction in Drosophila: new insights from nutritional geometry. Proceedings of the National Academy of Sciences 105: 2498-2503.

    Lee, S.-E., S.-Y. Lee, E.-J. Jo, M.-Y. Kim, M.-S. Yang et al., 2013 A case of taurine-containing drink induced anaphylaxis. Asia Pacific Allergy 3: 70-73.

    Lee, Y. J., S. S. Galoforo, C. M. Berns, J. C. Chen, B. H. Davis et al., 1998 Glucose deprivation-induced cytotoxicity and alterations in mitogen-activated protein kinase activation are mediated by oxidative stress in multidrug-resistant human breast carcinoma cells. Journal of Biological Chemistry 273: 5294-5299.

    Lehkozivova, J., J. Karovicova, Z. Kohajdova, M. Suhaj and I. Simonova, 2006 Isotachophoretic analysis of the artificial sweeteners and time-intensity sweetness evaluation of soft drinks. Żywność Nauka Technologia Jakość 13.

    Leips, J., and T. F. Mackay, 2000 Quantitative trait loci for life span in Drosophila melanogaster: interactions with genetic background and larval density. Genetics 155: 1773-1788.

    Leszczyniecka, M., T. Roberts, P. Dent, S. Grant and P. B. Fisher, 2001 Differentiation therapy of human cancer: basic science and clinical applications. Pharmacol Ther 90: 105-156.

    Levi, B., and M. J. Werman, 2003 Fructose and related phosphate derivatives impose DNA damage and apoptosis in L5178Y mouse lymphoma cells. The Journal of Nutritional Biochemistry 14: 49-60.

    Li, H., L. Zhang, H. Jin and S. Jin, 2014 Caffeine inhibits angiogenesis via induction of endothelial cell apoptosis. Molecular Biology of the Cell 25: 1.

    Li, S., K. Chen, X. Li, X. Zhang and S. V. Liu, 2010a A new cultivation system for studying chemical effects on the lifespan of the fruit fly. Exp Gerontol 45: 158-162.

    Li, Y., L. Liu and T. O. Tollefsbol, 2010b Glucose restriction can extend normal cell lifespan and impair precancerous cell growth through epigenetic control of hTERT and p16 expression. The FASEB journal 24: 1442-1453.

    Licht, B., K. Shaw, C. Smith, M. Mendoza, J. Orr et al., 1992 Characterization of caramel colour IV. Food and chemical toxicology 30: 365-373.

    Liloglou, T., N. G. Bediaga, B. R. Brown, J. K. Field and M. P. Davies, 2014 Epigenetic biomarkers in lung cancer. Cancer letters 342: 200-212.

    Lindseth, G. N., S. E. Coolahan, T. V. Petros and P. D. Lindseth, 2014 Neurobehavioral effects of aspartame consumption. Research in nursing & health 37: 185-193.

    Lindsley, D. L., and G. G. Zimm, 2012 The genome of Drosophila melanogaster. Academic Press.

    Lopez-Serra, L., and M. Esteller, 2008 Proteins that bind methylated DNA and human cancer: reading the wrong words. British journal of cancer 98: 1881-1885.

    Lorenzi, M., D. F. Montisano, S. Toledo and A. Barrieux, 1986 High glucose induces DNA damage in cultured human endothelial cells. Journal of Clinical Investigation 77: 322.

    Ludwig, D. S., K. E. Peterson and S. L. Gortmaker, 2001 Relation between consumption of sugar-sweetened drinks and childhood obesity: a prospective, observational analysis. Lancet 357: 505-508.

    Luna, M. P., and J. M. Aguilera, 2014 Kinetics of colour development of molten glucose, fructose and sucrose at high temperatures. Food biophysics 9: 61-68.

    Lushchak, O. V., B. M. Rovenko, D. V. Gospodaryov and V. I. Lushchak, 2011 Drosophila melanogaster larvae fed by glucose and fructose demonstrate difference in oxidative stress markers and antioxidant enzymes of adult flies. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology 160: 27-34.

    Lleu, P.-L., and R. Huxtable, 1992 Phospholipid methylation and taurine content of synaptosomes from cerebral cortex of developing rat. Neurochemistry international 21: 109-118.

    MacGregor, J., J. Tucker, I. Ziderman, C. Wehr, R. Wilson et al., 1989 Non-clastogenicity in mouse bone marrow of fructose/lysine and other sugar/amino acid browning products with in vitro genotoxicity. Food and chemical toxicology 27: 715-721.

    MacKenzie, K., B. Boysen, W. Field, S. Petsel, C. Chappel et al., 1992 Toxicity studies of caramel colour III and 2-acetyl-4 (5)-tetrahydroxybutylimidazole in F344 rats. Food and chemical toxicology 30: 417-425.

    Maes, P., Y. B. Monakhova, T. Kuballa, H. Reusch and D. W. Lachenmeier, 2012 Qualitative and quantitative control of carbonated cola beverages using 1H NMR spectroscopy. Journal of agricultural and food chemistry 60: 2778-2784.

    Malik, V. S., B. M. Popkin, G. A. Bray, J.-P. Després, W. C. Willett et al., 2010 Sugar-sweetened beverages and risk of metabolic syndrome and type 2 diabetes a meta-analysis. Diabetes care 33: 2477-2483.

    Marinovich, M., C. L. Galli, C. Bosetti, S. Gallus and C. La Vecchia, 2013 Aspartame, low-calorie sweeteners and disease: regulatory safety and epidemiological issues. Food and Chemical Toxicology 60: 109-115.

    Marins, J. S. R., L. M. Sassone, S. R. Fidel and D. A. Ribeiro, 2012 In vitro genotoxicity and cytotoxicity in murine fibroblasts exposed to EDTA, NaOCl, MTAD and citric acid. Brazilian Dental Journal 23: 527-533.

    Marquadt, H., and H. Marquadt, 1977 Induction of malignant transformation and mutagenesis in cell cultures by cancer chemothcrapeutic agents. Cancer 40: 1930-1934.

    Martínez Becerra, R., and J. Robles González, 1999 Methodology for the desing of bioassays in aquatic toxicity. Agronomía Colombiana 16: 40-45.

    Martínez, J. G., J. Pérez-Escuredo, P. Castro-Santos, C. Á. Marcos, J. L. L. Pendás et al., 2012 Hypomethylation of LINE-1, and not centromeric SAT-α, is associated with centromeric instability in head and neck squamous cell carcinoma. Cellular Oncology 35: 259-267.

    Martins, A. T., F. d. S. d. Santos, F. L. F. Scannavino, J. R. Pires, E. P. Zuza et al., 2010 Effect of sodium cyclamate on the rat fetal exocrine pancreas: a karyometric and stereological study. International Journal of Morphology 28: 899-904.

    Martins, M. R. I., and R. Azoubel, 2007 Effects of aspartame on fetal kidney: A morphometric and stereological study. International Journal of Morphology 25: 689-694.

    Marzio, A., C. Merigliano, M. Gatti and F. Vernì, 2014 Sugar and Chromosome Stability: Clastogenic Effects of Sugars in Vitamin B6-Deficient Cells. PLOS Genetics 10: e1004199.

    Massie, H. R., T. R. Williams and L. K. DeWolfe, 1989 Changes in taurine in aging fruit flies and mice. Experimental gerontology 24: 57-65.

    Mateo-Fernandez, M., R. Almagro-Berlanga, V. Moreno-Ariza, R. Merinas-Amo, A. Alonso-Moraga et al., 2014 Biological activities of two cola beverages and caffeine: Toxicity, DNA protecting effects, tumor grow inhibition and lifespan increase. Toxicology Letters 229: S179-S179.

    Mateo-Fernández, M., T. Merinas-Amo, Z. N. Fernández-Bedmar, M. Martínez-Jurado, R. Merinas-Amo et al., 2015a Use of single cell gel electrophoresis assessing DNA damage caused by chemopreventive agents in human leukaemia cells. A model for nutraceutical in vitro screening. Toxicology Letters 238: S70.

    Mateo-Fernández, M., T. Merinas-Amo, M. Moreno-Millán, Á. Alonso-Moraga and S. Demyda-Peyrás, 2016 In vivo and in vitro genotoxic and epigenetic effects of two types of cola beverages and caffeine: a multiassay approach. BioMed research international 2016.

    Mateo-Fernández, M., V. Moreno-Ariza, M. Balongo-Escobar, L. Luque-Bravo, Z. N. Fernández-Bedmar et al., 2015b Biological effects of classic and diet soda drinks assessed in in vivo and in vitro models. Toxicology Letters 238: S65.

    Mayer, D., 1991 Acesulfame-k. CRC Press.

    McCord, J. M., 2008 Superoxide dismutase, lipid peroxidation, and bell-shaped dose response curves. Dose-Response 6: dose-response. 08-012. McCord.

    McKay, J. A., and J. C. Mathers, 2011 Diet induced epigenetic changes and their implications for health. Acta Physiol (Oxf) 202: 103-118.

    Mendelson, D., and F. H. Sobels, 1974 The inhibiting effect of caffeine on the maternal repair of radiation-induced chromosome breaks in Drosophila. Mutat Res 26: 123-128.

    Merinas-Amo, M. T., R. Almagro-Berlanga, M. Mateo-Fernandez, F. Calahorro-Nunez, A. Alonso-Moraga et al., 2013a P10-01. Abstracts/Toxicology Letters 221S 59: S125.

    Merinas-Amo, T., I. Tasset-Cuevas, A. M. Díaz-Carretero, A. Alonso-Moraga and F. Calahorro, 2017 Role of Choline in the Modulation of Degenerative Processes: In Vivo and In Vitro Studies. Journal of medicinal food 20: 223-234.

    Merinas-Amo, T., I. Tasset-Cuevas, A. M. Díaz-Carretero, Á. Alonso-Moraga and F. Calahorro, 2016 In vivo and in vitro studies of the role of lyophilised blond Lager beer and some bioactive components in the modulation of degenerative processes. Journal of Functional Foods 27: 274-294.

    Merinas-Amo, T., L. Villalba-Benito, R. Almagro-Berlanga, M. Romero-Jimenez, M. Mateo-Fernandez et al., 2013b Toxicological, genotoxicological, antigenotoxicological, cytotoxicity and lifespan studies of beer and some components. Toxicology Letters 221: S124-S124.

    Messina, S. A., and R. Dawson Jr, 2002 Attenuation of Oxidative Damage to Dna by Tairome and Taurine Analogs, pp. 355-367 in Taurine 4. Springer.

    Migliore, L., R. Barale, E. Bosco, F. Giorgelli, M. Minunni et al., 1990 Genotoxicity of methylglyoxal: cytogenetic damage in human lymphocytes in vitro and in intesting cells of mice. Carcinogenesis 11: 1503-1507.

    Mishra, A., K. Ahmed, S. Froghi and P. Dasgupta, 2015 Systematic review of the relationship between artificial sweetener consumption and cancer in humans: analysis of 599,741 participants. International journal of clinical practice.

    Mochizuki, T., H. Satsu and M. Shimizu, 2002 Tumor necrosis factor α stimulates taurine uptake and transporter gene expression in human intestinal Caco‐2 cells. FEBS letters 517: 92-96.

    Mohammed, M., 2011 Assessment of mutagenic potentiality of stevioside in comparison with some other sweeteners using Drosophila.

    Moretton, C., G. Crétier, H. Nigay and J.-L. Rocca, 2011 Quantification of 4-methylimidazole in class III and IV caramel colors: validation of a new method based on heart-cutting two-dimensional liquid chromatography (LC-LC). Journal of agricultural and food chemistry 59: 3544-3550.

    Morohoshi, M., K. Fujisawa, I. Uchimuraa and F. Numano, 1996 Glucose-dependent interleukin 6 and tumor necrosis factor production by human peripheral blood monocytes in vitro. Diabetes 45: 954-959.

    Msagati, T. A., 2012 The chemistry of food additives and preservatives. John Wiley & Sons.

    Mukherjee, A., and J. Chakrabarti, 1997 In vivo cytogenetic studies on mice exposed to acesulfame-K—a non-nutritive sweetener. Food and chemical toxicology 35: 1177-1179.

    Mullokandov, E., W. Franklin and M. Brownlee, 1994 DNA damage by the glycation products of glyceraldehyde 3-phosphate and lysine. Diabetologia 37: 145-149.

    Nakao, H., C. Umebayashi, M. Nakata, Y. Nishizaki, K. Noda et al., 2003 Formaldehyde-induced shrinkage of rat thymocytes. Journal of pharmacological sciences 91: 83-86.

    Navarro-Escobar, E., M.-P. González-Rodríguez and C.-M. Ferrer-Luque, 2010 Cytotoxic effects of two acid solutions and 2.5% sodium hypochlorite used in endodontic therapy. Med Oral Patol Oral Cir Bucal 15: e90-94.

    Nehlig, A., and G. Debry, 1994 Potential genotoxic, mutagenic and antimutagenic effects of coffee: a review. Mutat Res 317: 145-162.

    Neves, M. F., V. G. Trombin, F. F. Lopes, R. Kalaki, P. Milan et al., 2012 The orange juice business A Brazilian perspective, pp. Approx. 175 p. in World consumption of beverages. Wageningen Academic Publishers, Wageningen.

    Nieminen, A.-L., T. L. Dawson, G. J. Gores, T. Kawanishi, B. Herman et al., 1990 Protection by acidotic pH and fructose against lethal injury to rat hepatocytes from mitochondrial inhibitors, ionophores and oxidant chemicals. Biochemical and biophysical research communications 167: 600-606.

    Nikitin, A. G., S. Navitskas and L. A. Gordon, 2008 Effect of varying doses of caffeine on life span of Drosophila melanogaster. J Gerontol A Biol Sci Med Sci 63: 149-150.

    Nikolaidis, G., O. Y. Raji, S. Markopoulou, J. R. Gosney, J. Bryan et al., 2012 DNA methylation biomarkers offer improved diagnostic efficiency in lung cancer. Cancer research 72: 5692-5701.

    Nomura, K., and T. Yamanouchi, 2012 The role of fructose-enriched diets in mechanisms of nonalcoholic fatty liver disease. The Journal of nutritional biochemistry 23: 203-208.

    Nowacki, M., J. Adamowicz, J. Olkowska, K. Pietkun, T. Kloskowski et al., 2014 Non-alcoholic beverages, unknown influence on cell proliferation - An in vitro study. Annals of Agricultural and Environmental Medicine 21: 112-113.

    Nuzhdin, S. V., E. G. Pasyukova, C. L. Dilda, Z. B. Zeng and T. F. Mackay, 1997 Sex-specific quantitative trait loci affecting longevity in Drosophila melanogaster. Proc Natl Acad Sci U S A 94: 9734-9739.

    Nyby, M. D., K. Abedi, V. Smutko, P. Eslami and M. L. Tuck, 2007 Vascular Angiotensin type 1 receptor expression is associated with vascular dysfunction, oxidative stress and inflammation in fructose-fed rats. Hypertension research 30: 451.

    Olive, P. L., and J. P. Banáth, 2006 The comet assay: A method to measure DNA damage in individual cells. Nature Protocols 1: 23-29.

    Olive, P. L., G. Frazer and J. P. Banath, 1993 Radiation-induced apoptosis measured in TK6-Human B-Lymphoblast cells using the comet assay. Radiation Research 136: 130-136.

    Oms-Oliu, G., M. A. Rojas-Graü, L. A. González, P. Varela, R. Soliva-Fortuny et al., 2010 Recent approaches using chemical treatments to preserve quality of fresh-cut fruit: A review. Postharvest Biology and Technology 57: 139-148.

    Orsolin, P. C., R. G. Silva-Oliveira and J. C. Nepomuceno, 2015 Modulating effect of synthetic statins against damage induced by doxorubicin in somatic cells of Drosophila melanogaster. Food Chem Toxicol 81: 111-119.

    Osgood, C., and S. Zimmering, 1979 Effects of caffeine on maternal repair systems in Drosophila melanogaster. Concentration-dependent reversals of the effects of caffeine on chromosome loss and autosome-autosome translocations induced by x-rays in the paternal genome. Mutat Res 63: 79-86.

    Ostertag, W., and J. Haake, 1966 The mutagenicity in Drosophila melanogaster of caffeine and of other compounds which produce chromosome breakage in human cells in culture. Zeitschrift für Vererbungslehre 98: 299-308.

    Ouyang, X., P. Cirillo, Y. Sautin, S. McCall, J. L. Bruchette et al., 2008 Fructose consumption as a risk factor for non-alcoholic fatty liver disease. Journal of hepatology 48: 993-999.

    Oyama, Y., H. Sakai, T. Arata, Y. Okano, N. Akaike et al., 2002 Cytotoxic effects of methanol, formaldehyde, and formate on dissociated rat thymocytes: a possibility of aspartame toxicity. Cell biology and toxicology 18: 43-50.

    Pandir, D., 2016 DNA damage in human germ cell exposed to the some food additives in vitro. Cytotechnology 68: 725-733.

    Pandurangan, M., G. Enkhtaivan, B. Mistry, M. Chandrasekaran, R. Noorzai et al., 2016 Investigation of role of aspartame on apoptosis process in HeLa cells. Saudi Journal of Biological Sciences 23: 503-506.

    Patey, A., G. Shearer, M. Knowles and W. Denner, 1985 Ammonia caramels: specifications and analysis. Food Additives & Contaminants 2: 107-112.

    Peycheva, E., R. Alexandrova and G. Miloshev, 2014 Application of the yeast comet assay in testing of food additives for genotoxicity. Lwt-Food Science and Technology 59: 510-517.

    Ping, J., Y.-y. Lei, L. Liu, T.-t. Wang, Y.-h. Feng et al., 2012 Inheritable stimulatory effects of caffeine on steroidogenic acute regulatory protein expression and cortisol production in human adrenocortical cells. Chemico-Biological Interactions 195: 68-75.

    Pitaksalee, R., Y. Sanvarinda, T. Sinchai, P. Sanvarinda, A. Thampithak et al., 2015 Autophagy Inhibition by Caffeine Increases Toxicity of Methamphetamine in SH-SY5Y Neuroblastoma Cell Line. Neurotoxicity Research 27: 421-429.

    Piwkowska, A., D. Rogacka, I. Audzeyenka, M. Jankowski and S. Angielski, 2011 High glucose concentration affects the oxidant‐antioxidant balance in cultured mouse podocytes. Journal of cellular biochemistry 112: 1661-1672.

    Poe, B. S., and K. L. O'Neill, 1997 Caffeine modulates heat shock induced apoptosis in the human promyelocytic leukemia cell line HL-60. Cancer Lett 121: 1-6.

    Pons, F. W., and P. Muller, 1990 Strong antimutagenic effect of caffeine on 9-aminoacridine-induced frameshift mutagenesis in Escherichia coli K12. Mutagenesis 5: 363-366.

    Prakash, G., B. Hosetti and B. Dhananjaya, 2014 Protective effect of caffeine on Ethyl methanesulfonate-induced wing primordial cells of Drosophila melanogaster. Toxicology international 21: 96.

    Qin, T., J. Jelinek, J. Si, J. Shu and J.-P. J. Issa, 2009 Mechanisms of resistance to 5-aza-2′-deoxycytidine in human cancer cell lines. Blood 113: 659-667.

    Rana, S., S. Kumar, N. Rathore, Y. Padwad and S. Bhushan, 2016 Nutrigenomics and its impact on life style associated metabolic diseases. Current genomics 17: 261-278.

    Randerath, K., K. L. Putman and E. Randerath, 1993 Flavor constituents in cola drinks induce hepatic DNA adducts in adult and fetal mice. Biochemical and Biophysical Research Communications 192: 61-68.

    Rayburn, A. L., J. Bouma and C. A. Northcott, 2001 Comparing the clastogenic potential of atrazine with caffeine using Chinese hamster ovary (CHO) cells. Toxicology letters 121: 69-78.

    Rayes, A. A., 2008 Effect of some drinks on the benificial probiotic bacteria and the structure of testis of male albino mice. Journal of Applied Sciences Research 4: 803-813.

    Redmon, T., 2003 Assessing the attitudes and bahaviors of pedestrians and drivers in traffic situations. Institute of Transportation Engineers. ITE Journal 73: 26.

    Reissig, C. J., E. C. Strain and R. R. Griffiths, 2009 Caffeinated energy drinks—a growing problem. Drug and alcohol dependence 99: 1-10.

    Reiter, L. T., L. Potocki, S. Chien, M. Gribskov and E. Bier, 2001 A systematic analysis of human disease-associated gene sequences in Drosophila melanogaster. Genome research 11: 1114-1125.

    Ren, N., J. Charlton and P. N. Adler, 2007 The flare gene, which encodes the AIP1 protein of Drosophila, functions to regulate F-actin disassembly in pupal epidermal cells. Genetics 176: 2223-2234.

    Rencüzoğulları, E., B. A. Tüylü, M. Topaktaş, H. B. Ila, A. Kayraldız et al., 2004 Genotoxicity of aspartame. Drug and chemical toxicology 27: 257-268.

    Renwick, A., J. Thompson, M. O'shaughnessy and E. Walter, 2004 The metabolism of cyclamate to cyclohexylamine in humans during long-term administration. Toxicology and applied pharmacology 196: 367-380.

    Reuzel, P., and C. van der Heijden, 1991 Long-Term Oral Toxicity Study with Acesulfame-K in Beagles. Acesulfame K., Marcel Dekker, New York: 71.

    Rizkalla, S. W., 2010 Health implications of fructose consumption: A review of recent data. Nutrition & metabolism 7: 82.

    Roberts, M. J., G. T. Wondrak, D. C. Laurean, M. K. Jacobson and E. L. Jacobson, 2003 DNA damage by carbonyl stress in human skin cells. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 522: 45-56.

    Robertson, K. D., 2005 DNA methylation and human disease. Nature Reviews Genetics 6: 597.

    Robertson, R. P., and J. S. Harmon, 2006 Diabetes, glucose toxicity, and oxidative stress: a case of double jeopardy for the pancreatic islet β cell. Free Radical Biology and Medicine 41: 177-184.

    Rohman, A., Y. B. C. Man and E. Noviana, 2012 Analysis of emulsifier in food using chromatographic techniques. Journal of Food and Pharmaceutical Sciences 1.

    Rojas‐Molina, M., J. Campos‐Sánchez, M. Analla, A. Muñoz‐Serrano and Á. Alonso‐Moraga, 2005 Genotoxicity of vegetable cooking oils in the Drosophila wing spot test. Environmental and molecular mutagenesis 45: 90-95.

    Roman-Gomez, J., A. Jimenez-Velasco, X. Agirre, J. A. Castillejo, G. Navarro et al., 2008 Repetitive DNA hypomethylation in the advanced phase of chronic myeloid leukemia. Leuk Res 32: 487-490.

    Romero-Jimenez, M., J. Campos-Sanchez, M. Analla, A. Munoz-Serrano and A. Alonso-Moraga, 2005 Genotoxicity and anti-genotoxicity of some traditional medicinal herbs. Mutat Res 585: 147-155.

    Rosendahl, A. H., C. M. Perks, L. Zeng, A. Markkula, M. Simonsson et al., 2015 Caffeine and Caffeic Acid Inhibit Growth and Modify Estrogen Receptor and Insulin-like Growth Factor I Receptor Levels in Human Breast Cancer. Clinical Cancer Research 21: 1877-1887.

    Ross, S. A., J. Dwyer, A. Umar, J. Kagan, M. Verma et al., 2008 Introduction: diet, epigenetic events and cancer prevention. Nutrition reviews 66: S1-S6.

    Rovenko, B. M., N. V. Perkhulyn, D. V. Gospodaryov, A. Sanz, O. V. Lushchak et al., 2015 High consumption of fructose rather than glucose promotes a diet-induced obese phenotype in Drosophila melanogaster. Comp Biochem Physiol A Mol Integr Physiol 180: 75-85.

    Saldana, T. M., O. Basso, R. Darden and D. P. Sandler, 2007 Carbonated beverages and chronic kidney disease. Epidemiology (Cambridge, Mass.) 18: 501.

    Salganik, R. I., 2001 The benefits and hazards of antioxidants: controlling apoptosis and other protective mechanisms in cancer patients and the human population. Journal of the American College of Nutrition 20: 464S-472S.

    Salozhin, S., E. Prokhorchuk and G. Georgiev, 2005 Methylation of DNA—one of the major epigenetic markers. Biochemistry (Moscow) 70: 525-532.

    Sarıkaya, R., M. Selvi and F. Erkoç, 2012 Evaluation of potential genotoxicity of five food dyes using the somatic mutation and recombination test. Chemosphere 88: 974-979.

    Sasaki, K., M. Takeda and M. Uchiyama, 1981 Toxicity, absorption and elimination of phosphoric acid triesters by killifish and goldfish. Bulletin of Environmental Contamination and Toxicology 27: 775-782.

    Sasaki, Y. F., S. Kawaguchi, A. Kamaya, M. Ohshita, K. Kabasawa et al., 2002 The comet assay with 8 mouse organs: results with 39 currently used food additives. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 519: 103-119.

    Schaffer, S. W., J. Azuma and M. Mozaffari, 2009 Role of antioxidant activity of taurine in diabetes This article is one of a selection of papers from the NATO Advanced Research Workshop on Translational Knowledge for Heart Health (published in part 1 of a 2-part Special Issue). Canadian journal of physiology and pharmacology 87: 91-99.

    Schernhammer, E. S., K. A. Bertrand, B. M. Birmann, L. Sampson, W. C. Willett et al., 2012 Consumption of artificial sweetener–and sugar-containing soda and risk of lymphoma and leukemia in men and women. The American journal of clinical nutrition 96: 1419-1428.

    Schiffman, S. S., 2012 Rationale for further medical and health research on high-potency sweeteners. Chemical senses 37: 671-679.

    Schuller-Levis, G. B., and E. Park, 2003 Taurine: new implications for an old amino acid. FEMS microbiology letters 226: 195-202.

    Seifert, S. M., J. L. Schaechter, E. R. Hershorin and S. E. Lipshultz, 2011 Health effects of energy drinks on children, adolescents, and young adults. Pediatrics: peds. 2009-3592.

    Sengar, G., and H. K. Sharma, 2014 Food caramels: a review. Journal of food science and technology 51: 1686-1696.

    Serra-Majem, L., L. Bassas, R. García-Glosas, L. Ribas, C. Inglés et al., 2003 Cyclamate intake and cyclohexylamine excretion are not related to male fertility in humans. Food Additives & Contaminants 20: 1097-1104.

    Shah, T., G. Purohit, S. P. Nair, B. Patel, Y. Rawal et al., 2014 Assessment of obesity, overweight and its association with the fast food consumption in medical students. J Clin Diagn Res 8: CC05-07.

    Shankar, P., S. Ahuja and K. Sriram, 2013 Non-nutritive sweeteners: Review and update. Nutrition 29: 1293-1299.

    Shao, A., and J. N. Hathcock, 2008 Risk assessment for the amino acids taurine, l-glutamine and l-arginine. Regulatory toxicology and pharmacology 50: 376-399.

    Shi, X., N. S. Dalal and A. C. Jain, 1991a Antioxidant behaviour of caffeine: efficient scavenging of hydroxyl radicals. Food Chem Toxicol 29: 1-6.

    Shi, X., N. S. Dalal and A. C. Jain, 1991b Antioxidant behaviour of caffeine: efficient scavenging of hydroxyl radicals. Food Chem Toxicol 29: 1-6.

    Simintzi, I., K. H. Schulpis, P. Angelogianni, C. Liapi and S. Tsakiris, 2007 The effect of aspartame on acetylcholinesterase activity in hippocampal homogenates of suckling rats. Pharmacological research 56: 155-159.

    Simon, B. R., S. D. Parlee, B. S. Learman, H. Mori, E. L. Scheller et al., 2013 Artificial sweeteners stimulate adipogenesis and suppress lipolysis independent of sweet taste receptors. Journal of Biological Chemistry: jbc. M113. 514034.

    Smith, L., I. Habib, S. Shirkey, B. Talon, A. Milne et al., 2011 Sexual dimorphism in the effect of a taurine supplemented diet on life span in adult Drosophila melanogaster. International Journal of Zoological Research 7: 34.

    Soffritti, M., F. Belpoggi, D. D. Esposti, L. Lambertini, E. Tibaldi et al., 2006 First experimental demonstration of the multipotential carcinogenic effects of aspartame administered in the feed to Sprague-Dawley rats. Environmental Health Perspectives: 379-385.

    Soffritti, M., F. Belpoggi, M. Manservigi, E. Tibaldi, M. Lauriola et al., 2010 Aspartame administered in feed, beginning prenatally through life span, induces cancers of the liver and lung in male Swiss mice. American journal of industrial medicine 53: 1197-1206.

    Soffritti, M., F. Belpoggi, E. Tibaldi, D. Degli Esposti and M. Lauriola, 2007 Life-span exposure to low doses of aspartame beginning during prenatal life increases cancer effects in rats. Environmental health perspectives 115: 1293.

    Sophos, N. A., and V. Vasiliou, 2003 Aldehyde dehydrogenase gene superfamily: the 2002 update. Chemico-biological interactions 143: 5-22.

    Suocheng, W., L. Huining, L. Haoqin, L. Luju and G. Zhu, 2016 Coca-Cola and Pepsi-Cola affect ovaries and follicles development. Biomedical Research 27.

    Suzuki, M. M., and A. Bird, 2008 DNA methylation landscapes: provocative insights from epigenomics. Nature Reviews Genetics 9: 465.

    Tahmassebi, J. F., M. S. Duggal, G. Malik-Kotru and M. E. J. Curzon, 2006 Soft drinks and dental health: A review of the current literature. Journal of Dentistry 34: 2-11.

    Tajkarimi, M., S. A. Ibrahim and D. Cliver, 2010 Antimicrobial herb and spice compounds in food. Food control 21: 1199-1218.

    Takatani, T., K. Takahashi, Y. Uozumi, E. Shikata, Y. Yamamoto et al., 2004 Taurine inhibits apoptosis by preventing formation of the Apaf-1/caspase-9 apoptosome. American Journal of Physiology-Cell Physiology 287: C949-C953.

    Takayama, S., A. Renwick, S. Johansson, U. Thorgeirsson, M. Tsutsumi et al., 2000 Long-term toxicity and carcinogenicity study of cyclamate in nonhuman primates. Toxicological Sciences 53: 33-39.

    Tamura, T., A. Fujii and H. Kusaba, 1979 Deleterious effect of short-term exposure to Coca-Cola on rats. Journal of Toxicological Sciences 4: 363-375.

    Tamura, T., H. Kusaba, A. Umezawa and A. Fujii, 1977 Study on toxicity of Coca-Cola. Journal of Toxicological Sciences 2: 65-66.

    Tasset-Cuevas, I., Z. Fernandez-Bedmar, M. Dolores Lozano-Baena, J. Campos-Sanchez, A. de Haro-Bailon et al., 2013 Protective Effect of Borage Seed Oil and Gamma Linolenic Acid on DNA: In Vivo and In Vitro Studies. Plos One 8.

    Taylor, J. D., R. K. Richards, R. G. Wiegand and M. S. Weinberg, 1968 Toxicological studies with sodium cyclamate and saccharin. Food and Cosmetics Toxicology 6: 313-327.

    Teff, K. L., S. S. Elliott, M. Tschöp, T. J. Kieffer, D. Rader et al., 2004 Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. The Journal of Clinical Endocrinology & Metabolism 89: 2963-2972.

    Ting, D. T., D. Lipson, S. Paul, B. W. Brannigan, S. Akhavanfard et al., 2011 Aberrant overexpression of satellite repeats in pancreatic and other epithelial cancers. Science 331: 593-596.

    Tóthová, T., J. Hodosy, K. Mettenburg, H. Fábryová, A. Wagnerová et al., 2013 No harmful effect of different Coca-cola beverages after 6months of intake on rat testes. Food and Chemical Toxicology 62: 343-348.

    Trewavas, A., and D. Stewart, 2003 Paradoxical effects of chemicals in the diet on health. Current opinion in plant biology 6: 185-190.

    Troen, A. M., E. E. French, J. F. Roberts, J. Selhub, J. M. Ordovas et al., 2007 Lifespan modification by glucose and methionine in Drosophila melanogaster fed a chemically defined diet. Age 29: 29-39.

    Tsai, P.-J., T.-Y. Yu, S.-H. Chen, C.-C. Liu and Y.-F. Sun, 2009 Interactive role of color and antioxidant capacity in caramels. Food research international 42: 380-386.

    Tsubono, Y., K. Ogawa, Y. Watanabe, Y. Nishino, I. Tsuji et al., 2001 Food frequency questionnaire as a screening test. Nutrition and Cancer-an International Journal 39: 78-84.

    Tucker, K. L., K. Morita, N. Qiao, M. T. Hannan, L. A. Cupples et al., 2006 Colas, but not other carbonated beverages, are associated with low bone mineral density in older women: The Framingham Osteoporosis Study. The American journal of clinical nutrition 84: 936-942.

    Türkez, H., and F. Geyikoğlu, 2010 The anti-genotoxic effect of taurine on aluminum sulphate-induced DNA damage in human peripheral lymphocytes. IUFS Journal of Biology 69: 25-32.

    Türkoğlu, Ş., 2007 Genotoxicity of five food preservatives tested on root tips of Allium cepa L. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 626: 4-14.

    Valadares, B., U. Graf and M. Spanó, 2008 Inhibitory effects of water extract of propolis on doxorubicin-induced somatic mutation and recombination in Drosophila melanogaster. Food and chemical toxicology 46: 1103-1110.

    Van Bao, T., I. Szabó, P. Ruzicska and A. Czeizel, 1974 Chromosome aberrations in patients suffering acute organic phosphate insecticide intoxication. Humangenetik 24: 33-57.

    van Eyk, A. D., 2015 The effect of five artificial sweeteners on Caco-2, HT-29 and HEK-293 cells. Drug and chemical toxicology 38: 318-327.

    Vartanian, L. R., M. B. Schwartz and K. D. Brownell, 2007 Effects of soft drink consumption on nutrition and health: a systematic review and meta-analysis. American Journal of Public Health 97: 667-675.

    Vaughn, A. E., and M. Deshmukh, 2008 Glucose metabolism inhibits apoptosis in neurons and cancer cells by redox inactivation of cytochrome c. Nature cell biology 10: 1477.

    Ventura, E. E., J. N. Davis and M. I. Goran, 2011 Sugar content of popular sweetened beverages based on objective laboratory analysis: focus on fructose content. Obesity (Silver Spring) 19: 868-874.

    Verner, A., S. Craig and W. Mc Guire, 2006 Effect of taurine supplementation on growth and development in preterm or low birth weight infants. Cochrane Database of Systematic Reviews 20074.

    Villatoro-Pulido, M., R. Font, M. I. De Haro-Bravo, M. Romero-Jiménez, J. Anter et al., 2009 Modulation of genotoxicity and cytotoxicity by radish grown in metal-contaminated soils. Mutagenesis 24: 51-57.

    von Rymon Lipinski, G.-W., and L. Y. Hanger, 2001 Acesulfame K. Food Science and Technology-New York-Marcel Dekker-: 13-30.

    Wang, G., V. Bhoopalan, D. Wang, L. Wang and X. Xu, 2015 The effect of caffeine on cisplatin-induced apoptosis of lung cancer cells. Exp Hematol Oncol 4: 5.

    Wang, X.-H., L. Andrae and N. J. Engeseth, 2002 Antimutagenic effect of various honeys and sugars against Trp-p-1. Journal of agricultural and food chemistry 50: 6923-6928.

    Watson, D., 2002 Food Chemical Safty vol 2, Additives. First published. Wood Head Publishing Limited 12: 283-292.

    Waye, J., and H. Willard, 1986 Structure, organization, and sequence of alpha satellite DNA from human chromosome 17: evidence for evolution by unequal crossing-over and an ancestral pentamer repeat shared with the human X chromosome. Molecular and cellular biology 6: 3156-3165.

    Wei, E. K., E. Giovannucci, J. Selhub, C. S. Fuchs, S. E. Hankinson et al., 2005 Plasma vitamin B 6 and the risk of colorectal cancer and adenoma in women. Journal of the National Cancer Institute 97: 684-692.

    Weisenberger, D. J., M. Campan, T. I. Long, M. Kim, C. Woods et al., 2005 Analysis of repetitive element DNA methylation by MethyLight. Nucleic acids research 33: 6823-6836.

    West, N., J. Hughes and M. Addy, 2000 Erosion of dentine and enamel in vitro by dietary acids: the effect of temperature, acid character, concentration and exposure time. Journal of oral rehabilitation 27: 875-880.

    Whitcutt, J., and E. Bey, 2008 Toxicity evaluation of synthetic food sweeteners by means of the Weaver Human Cell Test. South African Journal of Science 104: 36-36.

    WHO, 1983 Evaluation of certain additives and contaminants. Twenty‐seventh Report of the Joint FAO/WHO Expert Committee on Food Additives.

    Wild, L., and J. M. Flanagan, 2010 Genome-wide hypomethylation in cancer may be a passive consequence of transformation. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer 1806: 50-57.

    Wildman, R., 2001 Nutraceuticals: a brief review of historical and teleological aspects. Handbook of nutraceuticals and functional foods: 2-12.

    Wilson, A. S., B. E. Power and P. L. Molloy, 2007 DNA hypomethylation and human diseases. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer 1775: 138-162.

    Willett, W. C., 1994 Diet and health: what should we eat? Science 264: 532-537.

    Williams, K. B., 2008 Bone Density and Consumption of Cola Beverages. American Dental Hygienists Association 82: 7-7.

    Wyllie, A., 1981 Cell death: a new classification separating apoptosis from necrosis, pp. 9-34 in Cell death in biology and pathology. Springer.

    Xian-pei, H., C. Ke-ji, H. Zheng-feng, H. Wei-dong, C. Ke-dan et al., 2009 Glucose endothelial cytotoxicity and protection by Dan Gua-Fang, a Chinese herb prescription in huVEC in hyperglycemia medium. Journal of diabetes and its complications 23: 297-303.

    Xu, D., B. Zhang, G. Liang, J. Ping, H. Kou et al., 2012 Caffeine-induced activated glucocorticoid metabolism in the hippocampus causes hypothalamic-pituitary-adrenal axis inhibition in fetal rats. PLoS One 7: e44497.

    Yamori, Y., L. Liu, K. Ikeda, A. Miura, S. Mizushima et al., 2001 Distribution of twenty-four hour urinary taurine excretion and association with ischemic heart disease mortality in 24 populations of 16 countries: results from the WHO-CARDIAC study. Hypertension Research 24: 453-457.

    Yanders, A. F., and R. K. Seaton, 1962 The Lack of Mutagenicity of Caffeine in Drosophila. The American Naturalist 96: 277-280.

    Yang, A. S., M. R. Estécio, K. Doshi, Y. Kondo, E. H. Tajara et al., 2004 A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements. Nucleic acids research 32: e38-e38.

    Yang, X., Z. Zhang, Y. Feng, H. Ren, F. Liu et al., 2012 Effect of taurine on lifespan and antioxidant in Drosophila, pp. 206-209 in Biomedical Engineering and Biotechnology (iCBEB), 2012 International Conference on. IEEE.

    Yedjou, C., and P. Tchounwou, 2007 In-vitro cytotoxic and genotoxic effects of arsenic trioxide on human leukemia (HL-60) cells using the MTT and alkaline single cell gel electrophoresis (Comet) assays. Molecular and Cellular Biochemistry 301: 123-130.

    Yılmaz, S., and A. Uçar, 2014 A review of the genotoxic and carcinogenic effects of aspartame: does it safe or not? Cytotechnology 66: 875-881.

    Yılmaz, S., F. Unal, H. Aksoy, D. Yuzbasıoglu and M. Celik, 2008 Cytogenetic effects of citric acid and benzoic acid on allium chromosomes. Fresen Environ Bull 17: 1029-1037.

    Yun, J.-M., I. Jialal and S. Devaraj, 2011 Epigenetic regulation of high glucose-induced proinflammatory cytokine production in monocytes by curcumin. The Journal of Nutritional Biochemistry 22: 450-458.

    Yun, J. W., E. S. Shin, S. Y. Cho, S. H. Kim, C. W. Kim et al., 2008 The effects of BADGE and caffeine on the time-course response of adiponectin and lipid oxidative enzymes in high fat diet-fed C57BL/6J mice: correlation with reduced adiposity and steatosis. Exp Anim 57: 461-469.

    Zhao, E. H., B. Ergul and W. Zhao, 2015 Caffeine's Antioxidant Potency Optically Sensed with Double-Stranded DNA-Encased Single-Walled Carbon Nanotubes. Journal of Physical Chemistry B 119: 4068-4075.

    Zheng, J., F. L. Greenway, S. B. Heymsfield, W. D. Johnson, J. F. King et al., 2014 Effects of three intense sweeteners on fat storage in the C. elegans model. Chemico-biological interactions 215: 1-6.