Modulation of Phorbol Ester Induced Events by Dietary Corn Oil
Increased consumption of dietary corn oil, rich in linoleic acid, has been shown to have a protective effect on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumor promotion in mouse skin [Leyton et al., Cancer Res. 51:907–15 (1991)]. To investigate the molecular basis of this observation, it was hypothesized that the dietary lipids incorporated into the epidermal cell membrane modulate events associated with tumor promotion, specifically ornithine decarboxylase activity and hyperplasia, and subcellular distribution of protein kinase C activity. To test this hypothesis, weanling female SENCAR mice were fed modified AIN-76 diets containing 15% total fat for approximately four weeks. Corn oil and coconut oil were added to achieve three levels of linoleic acid: 0.8%, 4.5%, and 8.4% (1%, 7.9%, and 15% corn oil, respectively). Fatty acid analysis of each epidermal phospholipid fraction by gas chromatography revealed that increasing dietary linoleic acid was associated with an increase in phospholipid linoleate. Although TPA induction of ornithine decarboxylase was not significantly modified by dietary linoleate, TPA induced hyperplasia was decreased in the epidermis of mice fed the 8.4% linoleate diets compared to the other groups. Subcellular distribution of protein kinase C in the epidermis was altered by the different diets. In mice fed 0.8% linoleate, 69% of the protein kinase C activity was found in the cytosol compared to 78% and 74% for the mice fed 4.5% and 8.4% linoleate diets, respectively. It was also found that partially purified protein kinase C isolated from mouse epidermis was activated by linoleic acid in vitro, however, the extent of activation was less than that for arachidonic acid. These data suggest that the effect of dietary lipid on TPA tumor promotion may be mediated through modulation of protein kinase C.