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.

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.

• Authors: Shoji Fukushima, Hideki Wanibuchi, Keiichirou Morimura, Min Wei, Dai Nakae, Yoichi Konishi, Hiroyuki Tsuda, Nobuaki Uehara, Katsumi Imaida, Tomoyuki Shirai, Masae Tatematsu, Tetsuya Tsukamoto, Masao Hirose, Fumio Furukawa, Keiji Wakabayashi, Yukari Totsuka
• Journal: Japanese journal of cancer research : Gann (Jpn J Cancer Res) Vol. 93 Issue 10 Pg. 1076-82 (Oct 2002) ISSN: 0910-5050 [Print] Japan
• PMID: 12417036 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, toxicity)
• Rats
• Rats, Inbred F344