Studies on the spin state of 3-methylcholanthrene induced cytochrome P-450 from rat liver.
The time course of infuction of rat liver microsomal cytochrome P-450 by the polycyclic hydrocarbon 3-methylcholanthrene was followed by measuring the specific content of cytochrome P-450, benzpyrene hydroxylase activity, and the percent of cytochrome P-450 existing as the high-spin form (g equal to 7.9, 3.7 and 1.7) as determined by low temperature EPR spectroscopy. Significant increases in benzpyrene hydroxylase, cytochrome P-450 and high-spin ferric hemoprotein are seen twenty-four hours following 3-methylcholanthrene treatment. Administration of DL-ethionine prior to 3-methylcholanthrene treatment effectively blocks any increase in benzypyrene hydroxylase and cytochrome P-450 but not the increase in the levels of the high-spin species of the hemoprotein normally seen following 3-methylcholanthrene induction. In addition, partially purified cytochrome P-450 can be isolated from liver microsomes of 3-methylcholanthrene treated rats as low-spin ferric hemoprotein containing essentially no high-spin species (smaller than 1 per cent). This partially purified hemoprotein has the same substrate specificity as the microsomes from which it was derived. It is therefore concluded that the appearance of the high-spin form of cytochrome P-450, as quantitated by EPR, does not correlate with the induction of cytochrome P-450 and benezpyrene hydroxylase activity by 3-methylcholanthrene.
D000818:Animals; D001579:Benzopyrene Hydroxylase / Q000032:analysis; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D004578:Electron Spin Resonance Spectroscopy; D004790:Enzyme Induction; D005001:Ethionine / Q000494:pharmacology; D006420:Hemeproteins / Q000032:analysis; D008099:Liver / Q000187:drug effects; D008297:Male; D008748:Methylcholanthrene / Q000378:metabolism / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000032:analysis / Q000201:enzymology; D011485:Protein Binding; D051381:Rats; D013696:Temperature; D013997:Time Factors; D014316:Tritium
D006420:Hemeproteins; D014316:Tritium; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D001579:Benzopyrene Hydroxylase; D005001:Ethionine