Induction of drug metabolism. VII. Differences in P-420 hemoproteins from untreated and 3-methylcholanthrene-treated rats.

Cytochromes P-450 and P 1 -450 (P-448), found predominantly in hepatic microsomes from untreated and from 3-methylcholanthrene-treated rats, respectively, are reported to be distinct molecular entities. To test this hypothesis, a comparison was made of soluble P-420 hemoproteins obtained from membrane-bound P-450 hemoproteins by digesting microsomes with steapsin. Partially purified, soluble cytochromes P-420 and P 1 -420 from microsomes from untreated and 3-methylcholanthrene-treated rats, respectively, were found to differ in their electrophoretic mobilities and in the molar absorbances of their carbon monoxide complexes (P-420, 110 mM -1 cm -1 ; P 1 -420, 134 mM -1 cm -1 ); when caused to aggregate, cytochrome P-420 exhibited both type I (hexobarbital) and type II (aniline difference spectra, but aggregated cytochrome P 1 -420 exhibited a type II difference spectrum only. That cytochrome P 1 -450 is not simply a complex of cytochrome P-450 with 3-methylcholanthrene or its metabolites was demonstrated by the failure of soluble, purified cytochrome P 1 -420 from rats treated with tritiated 3-methylcholanthrene to exhibit radioactivity. These studies support the view that cytochromes P-450 and P 1 -450 are distinct molecular entities.