Existence of a no effect level for MeIQx hepatocarcinogenicity on a background of thioacetamide-induced liver damage in rats.
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.
Kang
Jin Seok
JS
Department of Pathology, Osaka City University Medical School,1-4-3 Asahi-machi, Osaka, 545-8585, Japan.
Wanibuchi
Hideki
H
Morimura
Keiichirou
K
Totsuka
Yukari
Y
Yoshimura
Isao
I
Fukushima
Shoji
S
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
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