Effect of vitamin E on arachidonic acid peroxidation and its binding to Chinese hamster V79 cell DNA
1991
Zhang, J.R. | Sevanian, A.
Following 24 h incubation in standard culture medium (containing 2 micromolar of arachidonic acid, AA), and 10 and 20 micromolar supplemented AA, approx. 55, 40 and 33%, respectively, of the fatty acid was incorporated into Chinese hamster V79 cell lipids. The AA content of cells increased 5 to 7-fold with the 10 and 20 micromolar supplementations of AA and, there was a correspondingly marked decrease in the proportion of AA incorporated into phospholipids (94 vs. 50 and 32%), whereas an increased percentage of AA was recovered in triacylglycerols (1 vs. 30 and 50%) and free fatty acids (1 vs. 3 and 8%). AA at 12 and 22 micromolar induced a 50 and 80% increase, respectively, in cellular content of thiobarbituric acid reactive substances (TBARS), an indication of increased peroxidation of cell lipids. This formation of TBARS was inhibited by vitamin E but not by indomethacin or SKF-525. Binding of [3H]AA-derived counts to DNA increased in parallel to the levels of cellular lipid peroxidation. Vitamin E added to the culture medium at 10(-4) M was readily taken up by the cells within 48 h and significantly reduced both lipid peroxidation and binding of AA-derived counts to DNA, without affecting AA uptake. Cell vitamin E content was significantly reduced following 24 h incubation in the presence of 10 and 20 micromolar supplemented AA. This study indicates that products of lipid peroxidation can bind to DNA in cultured cells, and points to a potential cyto- and geno-toxic risk posed by increased cellular AA content relative to anti-oxidant defenses.
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