The formation of chlorobenzene and benzene by the reductive metabolism of lindane in rat liver microsomes.
The major metabolite produced by incubating [14C]lindane with rat liver microsomes under anaerobic conditions was determined to be chlorobenzene, with lesser amounts of benzene also being formed. Using relatively high lindane concentrations (250 microM), four nonvolatile metabolites of lindane were also produced anaerobically, the predominant one being identified by mass spectrometry as tetrachlorocyclohexene (TCCH). TCCH, likewise, was reduced to chlorobenzene and benzene in microsomes under anaerobic conditions. Binding of [14C]lindane to microsomal protein occurred under aerobic as well as anaerobic incubation conditions; however, lindane protein binding was greatest in anaerobic incubations compared to those containing an atmosphere of air or 100% oxygen. Hemin reduced by dithionite also readily produced chlorobenzene and benzene from lindane. These results indicate that lindane interacts readily with heme and heme proteins, including cytochrome P-450, in the absence of oxygen to undergo multiple chloride eliminations forming chlorobenzene and benzene as end products.
Baker
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Nelson
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Van Dyke
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D000818:Animals; D001554:Benzene / Q000378:metabolism*; D001711:Biotransformation; D002384:Catalysis; D002722:Chlorobenzenes / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006427:Hemin / Q000378:metabolism; D001556:Hexachlorocyclohexane / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D013057:Spectrum Analysis / Q000379:methods
D002722:Chlorobenzenes; D001556:Hexachlorocyclohexane; D006427:Hemin; D003577:Cytochrome P-450 Enzyme System; D001554:Benzene; C031294:chlorobenzene