The male rat carcinogens limonene and sodium saccharin are not mutagenic to male Big Blue™ rats

Suzanne D. Turner, Helen Tinwell, Walter Piegorsch, Peter Schmezer, John Ashby

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Limonene and sodium saccharin are male rat specific carcinogens giving rise to renal and bladder tumours, respectively. Both compounds give negative results in genetic toxicity assays suggesting a non-genotoxic mode of action for their carcinogenicity. The α2U-globulin accumulation theory has been invoked to explain the renal carcinogenicity of limonene: the accumulation of micro masses of calcium phosphate in the bladder, coupled with a high pH environment in the male rat bladder, has been suggested to be responsible for the bladder carcinogenicity of sodium saccharin. The implication of these proposed mechanisms is that limonene and sodium saccharin will not be mutagenic to the rat kidney and bladder, respectively. This proposal has been evaluated by assessing the mutagenic potential of the two chemicals to male lacI transgenic (Big Blue™) rats. Male BigBlue™ rats were exposed for 10 consecutive days to either limonene in diet, at a dose level in excess of that used in the original National Toxicology Program gavage carcinogenicity bioassay, or to sodium saccharin in diet at the dose known to induce bladder tumours. The multi-site rat carcinogen 4-aminobiphenyl was used as a positive control for the experiment. Limonene failed to increase the mutant frequency in the liver or kidney of the rats, and sodium saccharin failed to increase the mutant frequency in the liver or bladder of the rats. 4-Aminobiphenyl was mutagenic to all three of these tissues. These results add further support to a non-genotoxic mechanism of carcinogenic action for both limonene and sodium saccharin.

Original languageEnglish (US)
Pages (from-to)329-332
Number of pages4
JournalMutagenesis
Volume16
Issue number4
StatePublished - Aug 8 2001
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Toxicology
  • Genetics(clinical)
  • Health, Toxicology and Mutagenesis

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    Turner, S. D., Tinwell, H., Piegorsch, W., Schmezer, P., & Ashby, J. (2001). The male rat carcinogens limonene and sodium saccharin are not mutagenic to male Big Blue™ rats. Mutagenesis, 16(4), 329-332.