Doxorubicin induced alterations in lipid metabolism of cultured myocardial cells.

Doxorubicin (DX) was found to inhibit the incorporation of [1-14C]linoleic acid and [1(3)-3H]glycerol into the major membrane phosphoglycerides, phosphatidylcholine and phosphatidylethanolamine of cultured myocardial cells in a dose-dependent manner (0.16-16 microM). It is suggested that DX affects de novo biosynthesis of these lipids. In contrast, DX-treatment of the cells stimulated incorporation of [1-14C]linoleic acid into triacylglycerol. The effects of DX on lipid metabolism were only demonstrable 20-24 hr after a 1 hr exposure of the cells to the drug indicating that DX exerts little or no direct effect on the enzymes participating in lipid synthesis and that the alterations in lipid metabolism induced by DX probably are secondary to inhibition of protein synthesis and progressive cell injury. Extensive peroxidative decomposition of membrane lipids appeared not to take place in the DX-treated cells as judged from fatty acid analysis of total membrane phosphoglyceride.