Microsomal activation of chlordane isomers to derivatives that irreversibly interact with cellular macromolecules.
Incubation of 14C-labeled cis and trans isomers of chlordane with cofactor-fortified mouse hepatic microsomes resulted in binding of insecticide-derived material to endogenous protein and RNA and to added DNA. The microsomes were prepared from male C57BL/6J mice. Chlordane is known to cause hepatocellular carcinoma in a similar strain. The highest concentrations of radioactive material bound to protein, followed by RNA and DNA. The cis isomer produced greater amounts of bound radioactivity, while binding from trans-chlordane was slight and, in the case of DNA, not detectable. Investigation of the effect of microsomal enzyme induction by chlordane isomers and phenobarbital on the yield of bound, chlordane-derived material gave mixed results. Generally, use of induced microsomes increased binding to protein and DNA and had no effect on binding to RNA. The inducers caused increased mixed-function oxidase activity, cytochrome P-450 content, and epoxide hydratase activity in experimental microsomes. Omission of the NADPH generating system from microsomal preparations had a variable effect on binding. Inhibition of epoxide hydratase reduced cis-chlordane-related binding to DNA to unmeasurable levels.
D000818:Animals; D002706:Chlordan / Q000378:metabolism* / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D007536:Isomerism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D012313:RNA / Q000378:metabolism
D002706:Chlordan; D012313:RNA; D004247:DNA; D010634:Phenobarbital