Metabolism studies of 3,3',4,4'-tetrachloroazobenzene. I. In vitro metabolic pathways with rat liver microsomes.
The metabolism of 3,3',4,4'-tetrachloroazobenzene (TCAB), an important environmental and occupational toxicant, by rat liver microsomes has been examined in a NADPH-generating system. The metabolic pathways were delineated by the combined use of high pressure liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). The rate of [14C]TCAB metabolism using induced microsomes was found to be 381 +/- 59 pmol/min/mg microsomal protein. Approximately 13% of the radioactivity from the [14C]TCAB substrate was covalently bound to the macromolecular pellet at the end of a 2-h incubation period. In addition, three distinct TCAB metabolites were isolated from the organic extracts and subsequently identified. Experiments with carbon monoxide, 2-diethylaminoethyl 2,2-diphenylvalerate hydrochloride (SKF 525-A), and control (uninduced) microsomes indicated the participation of the cytochrome P-450-dependent monooxygenases. The biological significance of both oxidative and reductive metabolic pathways were discussed. It was suggested that the generation of a reactive arene oxide intermediate mediated by oxidative enzymes may be crucial for some of the TCAB toxic effects observed in rodent tissues.
D000818:Animals; D001391:Azo Compounds / Q000633:toxicity*; D001711:Biotransformation; D002722:Chlorobenzenes / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D051381:Rats
D001391:Azo Compounds; D002722:Chlorobenzenes; C013279:3,4,3',4'-tetrachloroazobenzene; D009249:NADP