Effects of different inducers of cytochrome P450 on the mutagenesis of the tobacco-specific nitrosamine 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone (NNK) in Salmonella typhimurium TA1535.
The effects of six inducers of isoenzymes of cytochrome P450 on the mutagenicity of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in Salmonella typhimurium strain TA1535 by hamster liver S9 and microsomes were investigated. Comparisons of the effects of dimethylsulfoxide (DMSO) as solvent for NNK were also made. The inducing agents were Aroclor 1254 (AROC), 3-methylcholanthrene (MC), phenobarbital (PB), dexamethasone (DXM), ethanol (ETOH) and isosafrol (ISF). The number of histidine-independent colonies induced by NNK in saline mediated by S9 from the inducing agents was as follows: ISF = AROC greater than PB greater than MC greater than DXM greater than ETOH. AROC-induced microsomes produced the most revertants by NNK (saline) greater than MC greater than PB = DXM and ISF greater than ETOH. The number of revertant colonies induced by NNK in DMSO was significantly less than that by NNK in saline for both hamster liver S9 and microsomes irrespective of the inducing agent. The greatest inhibitory effect of DMSO was observed with ISF-induced S9.
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Department of Physiology and Pharmacology, School of Medicine, Loma Linda Health Sciences University, CA 92350.
D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D020111:Chlorodiphenyl (54% Chlorine); D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003907:Dexamethasone / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D008647:Mesocricetus; D008748:Methylcholanthrene / Q000494:pharmacology; D009154:Mutation; D009602:Nitrosamines / Q000378:metabolism / Q000633:toxicity*; D010634:Phenobarbital / Q000494:pharmacology; D012451:Safrole / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics
D001140:Aroclors; D007527:Isoenzymes; D009602:Nitrosamines; D020111:Chlorodiphenyl (54% Chlorine); D000431:Ethanol; D008748:Methylcholanthrene; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D012451:Safrole; C015959:isosafrole; D004121:Dimethyl Sulfoxide; D010634:Phenobarbital