Metabolism of the food-borne mutagen/carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in the rat: assessment of biliary metabolites for genotoxicity.
The absorption and kinetics of excretion of [14C]2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (MeIQx) was studied in male Sprague-Dawley rats. Within 72 hr of an oral dose of [14C]MeIQx (20 mg/kg) 33-56% of the radioactivity was excreted in the urine and 37-75% of the radioactivity in the faeces, which accounted for greater than 99% of the dose. Only low levels of radioactivity remained in the body. Radioactivity, when expressed per gram of tissue, was highest in the liver and kidney with smaller amounts detected in the lung and both the small and large intestines. Between 25 and 50% of a dose of MeIQx was recovered in the bile within 24 hr. Biliary metabolites were excreted over a long period of time with one radioactive fraction rapidly excreted at 2-3 hr and a second fraction excreted at 10-12 hr. The metabolites present in bile were assessed for genotoxicity using Salmonella typhimurium TA98 with or without hepatic S-9 activation and were found to be present as detoxified products. The residual mutagenic activity present in bile was attributed primarily to unmetabolized MeIQx.
Turesky
R J
RJ
Nestlé Research Centre, Nestec Ltd, Lausanne, Switzerland.
Aeschbacher
H U
HU
Malnoë
A
A
Würzner
H P
HP
D000818:Animals; D001646:Bile / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D008658:Inactivation, Metabolic; D008297:Male; D009152:Mutagenicity Tests; D011810:Quinoxalines / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains
D011810:Quinoxalines; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; D003577:Cytochrome P-450 Enzyme System