Lack of DNA-damaging activity of five non-nutritive sweeteners in the rat hepatocyte/DNA repair assay

Food and Chemical Toxicology

Volumn 38, Issue 4, 2000, Pages 335-338

  Jeffrey, A M ^a   Williams, G M ^a  

^a NEW YORK MEDICAL COLLEGE   (United States)

Author keywords

DNA damage; Genotoxic; Hepatocytes; Sweeteners; Unscheduled DNA synthesis

Indexed keywords

2 FLUORENYLAMINE; ACESULFAME; ASPARTAME; CYCLAMATE SODIUM; DIMETHYL SULFOXIDE; FLUORENE DERIVATIVE; SACCHARIN; SUCRALOSE; SWEETENING AGENT;

AMES TEST; ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CONSUMER; DNA DAMAGE; DNA REPAIR; DNA SYNTHESIS; GENOTOXICITY; MALE; MUTAGENICITY; NONHUMAN; RAT;

ANIMALS; DNA; DNA REPAIR; LIVER; MALE; MUTAGENICITY TESTS; RATS; RATS, INBRED F344; RATS, SPRAGUE-DAWLEY; SWEETENING AGENTS;

ANIMALIA;

EID: 0034112873     PISSN: 02786915     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0278-6915(99)00163-5     Document Type: Article

References (20)

1. Ashby J. The genotoxicity of sodium saccharin and sodium chloride in relation to their cancer-promoting properties. Food and Chemical Toxicology. 23:1985;507-519.
2. Bantle J. A., Fort D. J., Rayburn J. R., DeYoung D. J., Bush S. J. Further validation of FETAX: evaluation of the developmental toxicity of five known mammalian teratogens and non-teratogens. Drug and Chemical Toxicology. 13:1990;267-282.
3. Food and Drug Administration 21 CFR Part 172. Food Additives Permitted for Direct Addition to Food for Human Consumption; Sucralose. Federal Register. 63:(64):1988;16417-16433.
4. Hagiwara A., Fukushima S., Kitaori M., Shibata M., Ito N. Effects of three sweeteners on rat urinary bladder carcinogenesis initiated by N-butyl-N-(4-hydroxybutyl)-nitrosamine. Gann. 75:1984;763-768.
5. Harbach P. R., Wiser S. K., Smith A. L., Grzegorczyk C. R., Asron C. S. Strain differences in in vitro rat hepatocyte unscheduled DNA synthesis (UDS): effect of UV is independent of strain while increased sensitivity is apparent using Fischer-344 instead of Sprague-Dawley rats. Mutation Research. 252:1991;55-149.
6. IARC (1980a) IARC Monographs on the Evaluation of the Carcinogenic Risks to Humans. Vol. 22. Some Non-Nutritive Sweetening Agents. Cyclamates (cyclamic acid, sodium cyclamate, calcium cyclamate, cyclohexylamine and dicyclohexylamine). pp. 55-110. International Agency for Research on Cancer, Lyon.
7. IARC (1980b) IARC Monographs on the Evaluation of the Carcinogenic Risks to Humans. Vol. 22. Some Non-Nutritive Sweetening Agents. Saccharin (saccharin, sodium saccharin, calcium saccharin and ortho-toluenesulphonamide). pp. 111-170. International Agency for Research on Cancer, Lyon.
8. Ishii H. Incidence of brain tumors in rats fed aspartame. Toxicology Letters. 7:1981;433-437.
9. Jung R., Kreiling R. and Mayer D. G. (1991) Acesulfame-K: Studies for genotoxic effects. In Acesulfame-K, ed. D. G. Mayer and F. H. Kemper, pp. 87-104. Marcel Dekker, New York.
10. McQueen C. A., Way B. M., Williams G. M. Genotoxicity of carcinogens in human hepatocytes; application in hazard assessment. Toxicology and Applied Pharmacology. 96:1988;360-366.
11. Molinari S. V. (1984) Preclinical studies of aspartame in nonprimate animals. In Aspartame Physiology and Biochemistry, ed. L. D. Stegink and L. J. Filer Jr, pp. 289-306. Marcel Dekker, New York.
12. Ochi H., Tonomura A. Presence of unscheduled DNA synthesis in cultured human cells after treatment with sodium saccharin. Mutation Research. 54:1978;224.
13. Renwick A. G. Acceptable daily intake and the regulation of intense sweeteners. Food Additives and Contaminants. 7:1990;463-475.
14. Shephard S. E., Wakabayashi K., Nagao M. Mutagenic activity of peptides and the artificial sweetener aspartame after nitrosation. Food and Chemical Toxicology. 31:1993;323-329.
15. Takayama S., Sieber S. M., Adamson R. H., Thorgeirsson U. P., Dalgard D. W., Arnold L. L., Cano M., Eklund S., Cohen S. M. Long-term feeding of sodium saccharin to nonhuman primates: Implications for urinary tract cancer. Journal of the National Cancer Institute. 90:1998;2-3.
16. Whysner J., Williams G. M. Saccharin mechanistic data and risk assessment: Urine composition, enhanced cell proliferation, and tumor promotion. Pharmacology and Therapeutics. 71:1996;225-251.
17. Williams G. M. Detection of chemical carcinogens by unscheduled DNA synthesis in rat liver primary cell cultures. Cancer Research. 37:1977;1845-1851.
18. Williams G. M. (1988) Sweeteners: Health Effects. Princeton Scientific Publishing Co, Princeton, NJ.
19. Williams G. M. DNA reactive and epigenetic carcinogens. Experimental and Toxicologic Pathology. 44:1992;457-464.
20. Williams G. M., Mori H., McQueen C. A. Structure-activity relationships in the rat hepatocyte DNA-repair test for 300 chemicals. Mutation Research. 221:1989;263-286.