Restoration of hydroperoxide-dependent lipid peroxidation by 3-methylcholanthrene induction ofcytochrome P-448 in hepatoma microsomes

• Published in: FEBS letters 1986-12, Vol.209 (2), p.305-310
• Main Authors: Borrello, Silvia, Galeotti, Tommaso, Palombini, Guglieimo, Minotti, Giorgio
• Format: Article
• Language: English
• Subjects: 3-Methylcholanthrene; Cytochrome P-448; Lipid peroxidation; Microsome t-Butyl hydroperoxide; Morris hepatoma 9618A
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(86)81132-2

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 μM 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.