Lipid peroxidation in rat AH-130 hepatoma cells enriched in vitro with arachidonic acid.

Abstract

Tumor cells generally display low lipid peroxidation. A low content of polyunsaturated fatty acids in membrane phospholipids is a possible cause of their decreased susceptibility to lipid peroxidation. To investigate the importance of substrate availability in eliciting lipid peroxidation and to study cell viability in conditions of stimulated lipid peroxidation, AH-130 hepatoma cells were enriched with arachidonic acid. The enriched hepatoma cells showed increased mortality correlated with the increased incorporation of arachidonic acid in membrane phospholipids. When 0.5 mM arachidonic acid was added to hepatoma cells, this fatty acid reached a percentage content similar to that found in hepatocytes. Hepatoma cells enriched with this concentration were further incubated to determine their susceptibility to lipid peroxidation; mortality increased in parallel with increased thiobarbituric acid-reactive substance production. The highest mortality was in hepatoma cells treated with ascorbate/FeSO4. Mortality in normal cells was low, although they had a high production of thiobarbituric acid-reactive substances. The high capability of normal cells to metabolize the products of lipid peroxidation might explain the different viabilities of normal cells and hepatoma cells. It may therefore be possible to modify the composition of fatty acids of hepatoma cells in order to sensitize them to the toxic effect of prooxidant agents.