title: Existence of a no effect level for MeIQx hepatocarcinogenicity on a background of thioacetamide-induced liver damage in rats.
abstract: As exposure to heterocyclic amines might increase the risk of liver cancer, we investigated the carcinogenic potential of MeIQx under conditions of liver damage caused by TAA. Male, 6-week-old F344 rats (n = 280) were divided into 14 groups; groups 1-7 received TAA (0.03% in drinking water) and groups 8-14 received water for the first 12 weeks. Thereafter, the animals received MeIQx at doses from 0, 0.001, 0.01, 0.1, 1, 10 to 100 p.p.m. (groups 1-7 and 8-14, respectively) in pellet basal diet for 16 weeks. All survivors were killed at week 28 for assessment of numbers and areas of GST-P positive foci, considered to be pre-neoplastic lesions of the liver. Values were increased significantly in all the groups receiving TAA-->MeIQx compared to MeIQx alone (P < 0.01). Numbers of GST-P positive foci were significantly increased in groups 7 and 14 (treated with 100 p.p.m. MeIQx) as compared to 0 p.p.m.-MeIQx (groups 1 and 8) (P < 0.01), along with areas in group 14 compared to group 8 (P < 0.01). However, with the maximum likelihood method, the data for numbers of GST-P positive foci (groups 1-7 and groups 8-14) fitted the hockey stick regression model, representing no differences from groups 1-5 and from groups 8-13, despite a linear dose-dependent increase of MeIQx-DNA adducts from 0.1 to 100 p.p.m. We conclude that there is a no effect level for MeIQx hepatocarcinogenicity, even on a background of TAA-induced liver damage.
authors.affiliation: Department of Pathology, Osaka City University Medical School,1-4-3 Asahi-machi, Osaka, 545-8585, Japan.
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Kang
authors.forename: Hideki
authors.initials: H
authors.lastname: Wanibuchi
authors.forename: Keiichirou
authors.initials: K
authors.lastname: Morimura
authors.forename: Yukari
authors.initials: Y
authors.lastname: Totsuka
authors.forename: Isao
authors.initials: I
authors.lastname: Yoshimura
authors.forename: Shoji
authors.initials: S
authors.lastname: Fukushima
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005982:Glutathione Transferase / Q000378:metabolism; D007150:Immunohistochemistry; D008107:Liver Diseases / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D013853:Thioacetamide / Q000633:toxicity
chemical_list: D002273:Carcinogens; D018736:DNA Adducts; D011810:Quinoxalines; D013853:Thioacetamide; D044503:5-Methylcytosine; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; D005982:Glutathione Transferase