Lack of a dose-response relationship for carcinogenicity in the rat liver with low doses of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline or N-nitrosodiethylamine.

For a long period, it has been generally considered that carcinogens, particularly genotoxic ones, have no threshold in exerting their potential for cancer induction. However, the non-threshold theory can be challenged with regard to assessment of cancer risk to humans. Here we show that a food-derived, genotoxic hepatocarcinogen, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, forms DNA adducts at low doses, but does not induce glutathione S-transferase placental form (GST-P)-positive foci (considered to be preneoplastic lesions) or 8-hydroxy-2'-deoxyguanosine in rat liver. Moreover a N-nitroso compound, N-nitrosodiethylamine, at low doses was also found not to induce GST-P-positive foci in rat liver. These results imply that there is a no-observed effect level for hepatocarcinogenesis by these genotoxic carcinogens.