Restoration of hydroperoxide-dependent lipid peroxidation by 3-methylcholanthrene induction of cytochrome P-448 in hepatoma microsomes.
Microsomal membranes from the slow-growing Morris hepatoma 9618A catalyze, in the presence of t-butyl hydroperoxide, lower rates of lipid peroxidation than rat liver microsomes. The cytochrome P-450 content of hepatoma microsomes is about 40% that of the liver. SKF 525-A, an inhibitor of mixed-function oxidase, produces in hepatoma microsomes a P-450 type I binding spectrum similar to that of hepatic microsomes. The concentration of the inhibitor required for half-maximal spectral change is about 2 microM in both microsome types. SKF 525-A or ethylmorphine inhibit lipid peroxidation of normal and tumor microsomes to the same extent (about 60%). Treatment of the tumor-bearing rats with 3-methylcholanthrene increases the hepatoma cytochrome P-450 to values comparable to those of control membranes, although the hemoprotein has a peak in the CO-reduced difference absorption spectrum at 448 nm. The cytochrome P-448 induction is accompanied by an almost complete restoration of the hydroperoxide-dependent lipid peroxidation.
D000818:Animals; D019388:Cytochrome P-450 CYP1A2; D003580:Cytochromes / Q000378:metabolism*; D005036:Ethylmorphine / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007700:Kinetics; D008054:Lipid Peroxides / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008748:Methylcholanthrene / Q000494:pharmacology*; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D011335:Proadifen / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D011915:Rats, Inbred BUF
D003580:Cytochromes; D008054:Lipid Peroxides; D011374:Progesterone; D008748:Methylcholanthrene; D011335:Proadifen; D006861:Hydrogen Peroxide; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D005036:Ethylmorphine