Direct in vitro effects of bis (tri-n-butyltin)oxide on hepatic cytochrome P-450 |
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Authors: | Daniel W. Rosenberg George S. Drummond |
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Affiliation: | The Rockefeller University Hospital, New York, NY 10021, U.S.A. |
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Abstract: | Bis(tri-n-butyltin)oxide, an agriculturally important biocidal agent, when added in vitro to liver microsomes containing the phenobarbital-induced form of cytochrome P-450, produced a typical type I binding spectrum (an absorption maximum at 390 nm; an absorption minimum at 420 nm). Studies with microsomal preparations containing cytochrome P-448, induced by 3-methylcholanthrene or β-naphthoflavone, revealed that this hemeprotein was more susceptible to direct degradation by bis (tri-n-butyltin)oxide than was the uninduced or phenobarbital-induced forms of cytochrome P-450. The disappearance of spectrally detectable cytochrome P-450 was accompanied by an increase in cytochrome P-420. The formation of cytochrome P-420 was both time and temperature dependent, and it also occurred to a greater extent in microsomal preparations containing cytochrome P-448 than in microsomes containing the phenobarbital-induced form of cytochrome P-450. In all cases, the decreases in spectrally detectable cytochrome P-450 produced by the organotin were not accompanied by decreases in microsomal heme or cytochrome b5 content. The findings provide evidence for the direct interaction followed by conversion of cytochrome P-450 to cytochrome P-420 produced by a trialkyltin compound in vitro, and indicate that different susceptibilities to degradation exist within the various subspecies of this hemeprotein. |
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Keywords: | Address all correspondence to: Dr. Daniel W. Rosenberg The Rockefeller University Hospital 1230 York Ave. New York NY 10021. |
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