Fukushima Shoji, Wanibuchi Hideki, Morimura Keiichirou, Wei Min, Nakae Dai, Konishi Yoichi, Tsuda Hiroyuki, Uehara Nobuaki, Imaida Katsumi, Shirai Tomoyuki, Tatematsu Masae, Tsukamoto Tetsuya, Hirose Masao, Furukawa Fumio, Wakabayashi Keiji, Totsuka Yukari
Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Jpn J Cancer Res. 2002 Oct;93(10):1076-82. doi: 10.1111/j.1349-7006.2002.tb01208.x.
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.
长期以来，人们普遍认为致癌物，尤其是具有基因毒性的致癌物，在发挥其致癌潜力方面没有阈值。然而，关于对人类癌症风险的评估，非阈值理论可能会受到挑战。在此我们表明，一种食物来源的、具有基因毒性的肝癌致癌物2-氨基-3,8-二甲基咪唑并[4,5-f]喹喔啉，在低剂量时会形成DNA加合物，但不会在大鼠肝脏中诱导谷胱甘肽S-转移酶胎盘型（GST-P）阳性灶（被认为是癌前病变）或8-羟基-2'-脱氧鸟苷。此外，还发现一种N-亚硝基化合物N-亚硝基二乙胺在低剂量时也不会在大鼠肝脏中诱导GST-P阳性灶。这些结果表明，这些具有基因毒性的致癌物在肝癌发生方面存在未观察到效应的剂量水平。
