Microsomal activation of 2-amino-3-methylimidazo[4,5-f]quinoline, a pyrolysate of sardine and beef extracts, to a mutagenic intermediate

• Published in: Cancer research (Chicago, Ill.) Vol. 43; no. 12; pp. 5768 - 5774
• Main Authors: YAMAZOE, Y, SHIMADA, M, KAMATAKI, T, KATO, R
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.12.1983
• Subjects: Animals; Biological and medical sciences; Biotransformation; Chemical mutagenesis; Cytochrome P-450 Enzyme System - metabolism; Fishes; Hot Temperature; Male; Meat; Medical sciences; Microsomes, Liver - metabolism; Mutagenicity Tests; Mutagens - metabolism; Mutation; NADPH-Ferrihemoprotein Reductase - metabolism; Quinolines - metabolism; Quinolines - toxicity; Rats; Rats, Inbred Strains; Salmonella typhimurium - drug effects; Toxicology; Mutagenicity testing
• ISSN: 0008-5472; 1538-7445

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.