Saccharin: an epigenetic carcinogen/mutagen?

@article{Ashby1978SaccharinAE,
  title={Saccharin: an epigenetic carcinogen/mutagen?},
  author={John Ashby and John Styles and D Anderson and D. Paton},
  journal={Food and cosmetics toxicology},
  year={1978},
  volume={16 2},
  pages={
          95-103
        }
}
Saccharin, together with four of the impurities found in the commercial material and a further nine functional analogues gave negative results in the Salmonella reverse mutation assay of Ames et al. (Mutation Res. 1975, 31, 347) and the cell-transformation assay of Styles (Br. J. Cancer 1977, 36, 558). The significance of these and related in vitro results is evaluated within the context of the ability of commercial saccharin to cause bladder cancer in rats and dominant lethal effects in mice… 
The genotoxicity of sodium saccharin and sodium chloride in relation to their cancer-promoting properties.
  • J. Ashby
  • Chemistry, Medicine
    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
  • 1985
TLDR
It is suggested that the recorded genotoxic and cancer-promoting activities of these chemicals will only become apparent at elevated dose levels that define them as significant contributors to the biological medium (solvent) rather than as trace xenobiotic toxins (solutes).
Hepatocarcinogenesis in the rat: the effect of promoters and carcinogens in vivo and in vitro.
TLDR
The role of a number of factors in liver carcinogenesis is described, as investigated with both in vivo and in vitro models.
Toxicology of saccharin.
  • D. Arnold
  • Medicine
    Fundamental and applied toxicology : official journal of the Society of Toxicology
  • 1984
TLDR
It seems certain that this latest saccharin controversy may result in changes to the regulations dealing with food additives, as the number of chronic/carcinogenic studies conducted to assess its safety is reflected.
GENOTOXIC AND EPIGENETIC CARCINOGENS: THEIR IDENTIFICATION AND SIGNIFICANCE
  • G. Williams
  • Chemistry, Medicine
    Annals of the New York Academy of Sciences
  • 1983
TLDR
Specific classes of carcinogens have been assigned to two types, genotoxic, which are capable of reacting with and damaging DNA, and epigenetic, which do not damage DNA but produce other biological effects that result in the production of tumors.
Saccharin: a toxicological and historical perspective.
TLDR
While the toxicological data indicate that saccharin is probably the agent solely responsible for the bladder tumors observed in second generation male rats, the epidemiological studies provide, at best, an equivocal relationship between the consumption of sacchar in and bladder cancer.
Safety of Saccharin and Its Current Status of Regulation in the World
Department of Science and Technology Education for Life, Seoul National University of EducationAbstract Saccharin was reported to cause urinary bladder cancer in male rats when fed at high doses in a
Two-generation saccharin bioassays.
  • D. Arnold
  • Medicine
    Environmental health perspectives
  • 1983
TLDR
The results from these studies clearly show that when rats were exposed to diets containing 5 or 7.5% sodium saccharin from the time of conception to death, an increased frequency of urinary bladder cancers was found, predominantly in the males.
Mutagenicity study of Remsen-Fahlberg saccharin and contaminants.
TLDR
Results do not indicate mutagenic and therewith correlated carcinogenic potential of saccharin, but they emphasize the possible activity of contaminants.
The present lack of evidence for unique rodent germ-cell mutagens.
TLDR
Re-evaluation of the GeneTox literature has failed to find substantive evidence that any of these chemicals have been unequivocally established as having unique mutagenic activity in germ cells, and the general observation that rodent germ-cell mutagens are also genotoxic in somatic cells in vivo remains valid.
The effects of saccharin on the development of neoplastic lesions initiated with N-methyl-N-nitrosourea in the rat urothelium.
TLDR
The results in dead and moribund animals indicated that saccharin served as a tumor promoter in this two-stage carcinogenesis model system by decreasing the latency period of the lesions.
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