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

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

Research output: Contribution to journalArticle

61 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1076-1082
Number of pages7
JournalJapanese Journal of Cancer Research
Volume93
Issue number10
DOIs
Publication statusPublished - 01-10-2002

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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