N-benzylimidazole, a potent inducer of rat liver enzymes involved in mutagenic activation of various carcinogens.
The effects of N-benzylimidazole (BI) on mutagenic activation of six groups of carcinogens were studied with the Ames liquid incubation assay. Intragastric (i.g.) treatment of male Wistar rats for 3 days with BI produced an over 3-fold induction of hepatic microsomal cytochrome P-450 (CYP). The mutagenic activities of five N-nitrosamines on S. typhimurium TA100 and two arylamines on TA98 were induced up to 5 times above controls and much higher inductions on strain TA98 were observed with aflatoxin B1, two polycyclic hydrocarbons, two aminoazo compounds and six amino acid pyrolysates, which are all known to be metabolically activated by CYP I and/or II species. Compared with the reported results for rats treated with polychlorobiphenyls (PCB), the numbers of revertant colonies were the same or higher (0.7-1.8-fold), indicating that BI and PCB show a similar pattern of induction of CYP-dependent properties. However, intraperitoneally treated liver S9 was inferior to the i.g. treated S9 for all the mutagenic activations of 18 carcinogens. In conclusion, these results demonstrate the use of BI for metabolic induction to be an effective alternative for induction with either PCB or a combination of phenobarbital and beta-naphthoflavone.
Mori
Y
Y
Radioisotope Laboratory, Gifu Pharmaceutical University, Japan.
Iimura
K
K
Hirano
K
K
D000284:Administration, Oral; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004247:DNA / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D005798:Genes, Bacterial / Q000187:drug effects; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects* / Q000201:enzymology; D008110:Liver Extracts / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009152:Mutagenicity Tests / Q000379:methods; D009929:Organ Size / Q000187:drug effects; D014176:Protein Biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012486:Salmonella typhimurium / Q000235:genetics
D000317:Adrenergic alpha-Antagonists; D002273:Carcinogens; D007093:Imidazoles; D008110:Liver Extracts; C017062:1-benzylimidazole; D004247:DNA; D003577:Cytochrome P-450 Enzyme System