Loss of 3-methylcholanthrene-inducible form of cytochrome P-450 in liver microsomes following administration of carbon disulfide in C57BL/6 Cr mice.

Early after administration of CS2 to untreated, phenobarbital (PB)-and 3-methylcholanthrene (3-MC)-pretreated C57BL/6 Cr mice: (1) the loss of cytochrome P-450 was enhanced by pretreatment with both inducers, but to a greater extent with 3-MC; (2) the decrease in 7-ethoxyresorufin (ER) O-deethylation activity was much greater than that of cytochrome P-450 in untreated and PB-pretreated mice, but both paralleled values in 3-MC-pretreated mice, in which ER O-deethylation activity was induced markedly, (3) the peak of the carbon monoxide-difference spectrum of microsomal reduced cytochrome P-450 (about 448 nm) in 3-MC-pretreated mice shifted toward 450 nm after administration of increasing doses of CS2; (4) similar tendencies were observed in vitro in items (1) to (3); (5) electrophoresis of microsomal proteins revealed a loss of each protein band induced by PB and 3-MC following CS2 administration; (6) in the reconstituted monooxygenase system using partially purified cytochrome P-450 and P-448 forms from PB- and 3-MC-treated rats, CS2 suppressed the drug-metabolizing activities exhibited by the P-448 form but had little or no effect on those by the P-450 form; and (7) in n-octylamine difference spectra of microsomes, loss of the 3-MC-induced high spin form of cytochrome P-450 was evident. These results indicate that the 3-MC-inducible form of cytochrome P-450 was more susceptible to CS2 than the PB-inducible form. The hepato-necrogenic action of CS2 was not enhanced by PB or 3-MC pretreatment in mice.