Direct in vitro effects of bis(tri-n-butyltin)oxide on hepatic cytochrome P-450.
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 beta-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.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003580:Cytochromes / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D014220:Trialkyltin Compounds / Q000494:pharmacology*
D003580:Cytochromes; D014220:Trialkyltin Compounds; C005961:bis(tri-n-butyltin)oxide; C013464:cytochrome P420; D003577:Cytochrome P-450 Enzyme System