THE TUMOR PROMOTER 12-0-TETRADECANOYLPHORBOL-13-ACETATE INCREASES THE ACTIVITIES OF SOME PEROXISOME-ASSOCIATED ENZYMES IN INVITRO-CELL CULTURE

A study was conducted on the effects of 12O-tetradecanoyl-phorbol-13-acetate (TPA) on peroxisomal enzyme activities in mouse embryo fibroblasts C3H/10T1/2 C18 cells and chemically transformed C3H/10T1/2 MCA16 cells. TPA is a potent tumour promoter and treatment with this compound of the two cell lines induced peroxisomal fatty acid .beta.-oxidation, carnitine acetyltranferase, palmitoyl-CoA hydrolase, and catalase activities after 240 h of treatment. Stimulation of the corresponding enzyme activities was dose-related and cycloheximide inhibited the TPA-induced enzyme activities, except that of carnitine acetyltransferase. The MCA16 cells appeared to be more sensitive than the C18 cells in inducing peroxisome-associated enzyme activities after TPA treatment. The activities of the microsomal marker, NADPH-cytochrome c reductase and the mitochondrial marker, glutamate dehydrogenase were not enhanced by TPA treatment. The results indicate that TPA has peroxisomal effects and may be classified as a peroxisome proliferator.