Microsomal activation of 2-amino-3-methylimidazo[4,5-f]quinoline, a pyrolysate of sardine and beef extracts, to a mutagenic intermediate.
The mechanism involved in the metabolic activation of 2-amino-3-methylimidazo[4,5-f]quinoline, which is a pyrolysate isolated from broiled foods, to a mutagenic intermediate was studied in vitro. In a system containing hepatic microsomes and reduced nicotinamide adenine dinucleotide phosphate, 2-amino-3-methylimidazo[4,5-f]quinoline was converted to a product which was directly mutagenic to Salmonella typhimurium. The structure of the mutagenic metabolite was determined as the 2-N-hydroxy derivative on the basis of the chemical properties and the mass spectral evidence of the azoxy adduct with o-nitrosotoluene. The activation reaction was mediated by microsomal enzymes and was inhibited by carbon monoxide, 7,8-benzoflavone, and other chemicals which were known to inhibit the cytochrome P-450-dependent reaction. With the use of four forms of purified cytochrome P-450, the N-hydroxylation of 2-amino-3-methylimidazo[4,5-f]quinoline and the induction of the reverse mutation of the bacteria were clearly demonstrated to be catalyzed mainly by a high-spin form of cytochrome P-450, P-448 II-a.
D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005399:Fishes; D006358:Hot Temperature; D008297:Male; D008460:Meat; D008862:Microsomes, Liver / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism*; D009154:Mutation; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D011804:Quinolines / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects
D009153:Mutagens; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase