title: 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.affiliation: Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. fukuchan@med.osaka-cu.ac.jp
authors.forename: Shoji
authors.initials: S
authors.lastname: Fukushima
authors.forename: Hideki
authors.initials: H
authors.lastname: Wanibuchi
authors.forename: Keiichirou
authors.initials: K
authors.lastname: Morimura
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.forename: Dai
authors.initials: D
authors.lastname: Nakae
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Konishi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuda
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Uehara
authors.forename: Katsumi
authors.initials: K
authors.lastname: Imaida
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shirai
authors.forename: Masae
authors.initials: M
authors.lastname: Tatematsu
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: Masao
authors.initials: M
authors.lastname: Hirose
authors.forename: Fumio
authors.initials: F
authors.lastname: Furukawa
authors.forename: Keiji
authors.initials: K
authors.lastname: Wakabayashi
authors.forename: Yukari
authors.initials: Y
authors.lastname: Totsuka
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D018736:DNA Adducts / Q000032:analysis; D004052:Diethylnitrosamine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005982:Glutathione Transferase / Q000032:analysis; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced; D011810:Quinoxalines / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D002273:Carcinogens; D018736:DNA Adducts; D011810:Quinoxalines; D004052:Diethylnitrosamine; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; D005982:Glutathione Transferase