Abstract
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.
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