Prostaglandin H synthase-dependent formation of the direct-acting mutagen 2-nitro-3-methylimidazo[4,5-f]quinoline (nitro-IQ) from IQ.
The mutagenic effects of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) following activation by ram seminal vesicle microsomes (RSVM, a source of prostaglandin H synthase, PHS) were studied in Salmonella typhimurium tester strains possessing elevated levels of acetyl-CoA: arylamine N-acetyltransferase (NAT). The metabolites formed by RSVM were extracted and fractionated by high pressure liquid chromatography (HPLC). One isolable product accounted for most of the direct-acting mutagenicity observed in the extracts. The metabolite was identified as 2-nitro-3-methylimidazo[4,5-f]quinoline (nitro-IQ). Since nitro-IQ is a potent direct-acting mutagen, its role in IQ genotoxicity warrants further study.
Morrison
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LD
Guelph-Waterloo Centre for Graduate Work in Chemistry, Department of Chemistry and Biochemistry, University of Guelph, Ont. Canada.
Eling
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TE
Josephy
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PD
D000818:Animals; D001711:Biotransformation; D066298:In Vitro Techniques; D008297:Male; D008861:Microsomes / Q000201:enzymology; D016296:Mutagenesis / Q000187:drug effects*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011804:Quinolines / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D012669:Seminal Vesicles / Q000201:enzymology; D012756:Sheep
D009153:Mutagens; D011804:Quinolines; C071417:2-nitro-3-methylimidazo(4,5-f)quinoline; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D011451:Prostaglandin-Endoperoxide Synthases