Microsomal metabolism of the food mutagen 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]-quinoxaline to mutagenic metabolites.
Heterocyclic aromatic amines are formed in the crust of meat during ordinary cooking. These aromatic amines are potent bacterial mutagens and also potent rodent carcinogens. 2-Amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline (DiMeIQx) is one of the more abundant heterocyclic aromatic amines, accounting for approximately 20% of the mutagenic material found in cooked meat. DiMeIQx is metabolically activated, by hepatic microsomes from PCB treated rats, to two major and three minor metabolites. One major and one minor metabolite were identified as 2-hydroxyamino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline and 3,4,8-trimethyl-2-nitro-3H-imidazo[4,5-f]quinoxaline, respectively, confirmed by comparison of HPLC retention times, and UV and mass spectra of synthetic standards. Both metabolites were mutagenic in Salmonella typhimurium TA98 without metabolic activation. The other major metabolite was identified as 2-amino-8-hydroxymethyl-3,4-dimethyl-3H-imidazo[4,5-f]quinoxaline by mass and NMR spectral analysis. The two remaining minor metabolites were identified as the 2-hydroxyamino- and 2-nitro- derivatives of 2-amino-8-hydroxymethyl-3,4-dimethyl-3H-imidazo]4,5-f]quinoxaline by UV and mass spectral analysis. Both of these metabolites were mutagenic in S. typhimurium TA98 without metabolic activation.
Frandsen
H
H
Institute of Toxicology, National Food Agency, Søborg, Denmark.
Nielsen
P A
PA
Grivas
S
S
Larsen
J C
JC
D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005506:Food Contamination; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism*; D015394:Molecular Structure; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism* / Q000633:toxicity; D011810:Quinoxalines / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013056:Spectrophotometry, Ultraviolet
D009153:Mutagens; D011810:Quinoxalines; C042052:2-amino-3,7,8-trimethylimidazo(4,5-f)quinoxaline