||Dehydrogenation: A Previously Unreported Pathway of Lindane Metabolism in Mammals.
Chadwick, Robert W. ;
Chuang, Lucy T. ;
Williams., Katherine ;
||National Environmental Research Center, Research Triangle Park, N.C. Pesticides and Toxic Substances Effects Lab.
Chlorine organic compounds ;
In vivo analysis ;
In vitro analysis ;
Toxic substances ;
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The study presents evidence for the dehydrogenatin of lindane by a hepatic microsomal mixed-functin oxidase system. Preliminary investigation established that the incubation of lindane with rat liver homogenates produces a chlorinated, nonpolar compound identified as hexachlorocyclohexene. Differential centrifugation resulted in the sedimentation of most of the dehydrogenase activity in the microsomal fraction. Optimum in vitro assay conditions were established and it was found that the dehydrogenase system required molecular oxygen and reduced pyridine nucleotide coenzyme for maximum activity. Inhibition by SKF 525-A and CO suggested that the enzyme was cytochrome P-450 dependent. Lack of inhibition by cyanide indicated that the cytochrome b5 desaturase system was probably not involved. Pretreatment of rats with DDT, which stimulates lindane metabolism, also induced significantly higher dehydrogenase activity. Both the in vivo and in vitro metabolism of hexachlorocyclohexene produced previously identified lindane metabolites.