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

Jpn J Cancer Res. 2002 Oct;93(10):1076-82. doi: 10.1111/j.1349-7006.2002.tb01208.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogens / toxicity*
  • DNA Adducts / analysis
  • Diethylnitrosamine / toxicity*
  • Dose-Response Relationship, Drug
  • Glutathione Transferase / analysis
  • Liver Neoplasms, Experimental / chemically induced*
  • Male
  • Precancerous Conditions / chemically induced
  • Quinoxalines / metabolism
  • Quinoxalines / toxicity*
  • Rats
  • Rats, Inbred F344

Substances

  • Carcinogens
  • DNA Adducts
  • Quinoxalines
  • Diethylnitrosamine
  • 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline
  • Glutathione Transferase