Superoxide-dependent lipid peroxidation and vitamin E content of microsomes from hepatomas with different growth rates.
Lipid peroxidation of microsomal membranes isolated from rat liver, and Morris hepatomas 9618A (slow-growing) and 3924A (fast-growing) was induced by superoxide radicals generated by the action of xanthine oxidase on xanthine. The peroxidation, measured as malondialdehyde and lipid hydroperoxide formation, was optimized with regard to iron concentration and chelation of iron by ADP. In such conditions hepatoma microsomes catalyze lower rates of lipid peroxidation than the normal counterpart. However, while microsomes from hepatoma 3924A show a marked decrease in both the malondialdehyde and hydroperoxide production rates, microsomes from hepatoma 9618A differ moderately from the control, mainly in the long-term production of hydroperoxides. It is also reported here that the 9618A microsomes partially lack cytochrome P-450 (about 40% deficiency), but they have a fatty acid composition similar to that of control. No differences were found in the content of vitamin E between normal and hepatoma 3924A microsomes. Moreover, induction of vitamin E deficiency in hepatoma 3924A microsomes does not influence the rate of either malondialdehyde or lipid hydroperoxide production. On the basis of these results and previous data on the lipid composition of hepatoma 3924A microsomes it is proposed that the high resistance to superoxide-dependent lipid peroxidation of hepatoma 3924A microsomes is related to the low substrate availability rather than the content of membrane antioxidants; and a limitation only in the propagation phase characterizes the hepatoma 9618A microsomal lipid peroxidation and would be due to the partial deficiency of the endogenous propagating agent, cytochrome P-450.
Borrello
S
S
Minotti
G
G
Palombini
G
G
Grattagliano
A
A
Galeotti
T
T
D000818:Animals; D002455:Cell Division; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000096:biosynthesis*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000494:pharmacology*; D014810:Vitamin E / Q000378:metabolism*
D005231:Fatty Acids, Unsaturated; D008054:Lipid Peroxides; D013481:Superoxides; D014810:Vitamin E