thioacetamide and 2-amino-3-8-dimethylimidazo(4-5-f)quinoxaline

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.

Topics: 5-Methylcytosine; Animals; Carcinogens; Chemical and Drug Induced Liver Injury; Chromatography, High Pressure Liquid; DNA Adducts; Dose-Response Relationship, Drug; Glutathione Transferase; Immunohistochemistry; Liver Diseases; Liver Neoplasms, Experimental; Male; Quinoxalines; Rats; Thioacetamide