DIETARY FATTY-ACID MODULATION OF EVENTS ASSOCIATED WITH MOUSE SKIN TUMOR PROMOTION

Increasing levels of dietary corn oil have been correlated with inhibi tion of 12-0-tetradecanoyl-phorhol-13-acetate-(TPA) promoted skin tumo rigenesis in mice (Leyton et al. Cancer Res. 51, 907-915, 1991). This study was undertaken to assess the effects of dietary corn oil on seve ral events associated with tumor promotion. Three semipurified diets c ontaining 15% (wt/wt) total fat with increasing levels of linoleate (0 . 8%, 4.5%, and 8.4%) supplied hy corn oil were fed to mice for at lea st four weeks. Although incorporation of linoleate into epidermal phos phatidyl-choline increased with increasing amounts of dietary corn oil , the elongated desaturated product of linoleate, arachidonate, was si milar or decreased slightly in mice fed the three diets. Minimal activ ity of delta6-desaturase, the rate-limiting enzyme in the conversion o f linoleate to arachidonic acid, was found in the epidermis compared w ith the liver, suggesting that linoleate is not converted to arachidon ic acid in the skin. Subcellular distribution of protein kinase C was altered in mice fed 0.8% linoleate, where 69% of protein kinase C acti vity was in the cytosol compared with 78% and 74% for groups fed 4.5% and 8.4% linoleate, respectively. Activation of partially purified pro tein kinase C isolated from mouse epidermis by linoleate was significa ntly lower (p < 0.01) than that isolated by arachidonic acid. TPA-indu ced vascular permeability was significantly greater (p < 0.05), wherea s hyperplasia 48 hours after TPA treatment was significantly lower, in mice fed the 8.4% linoleate diet. However, TPA induction of ornithine decarboxylase activity did not appear to be significantly modified by dietary linoleate. These data suggest that cellular processes associa ted with carcinogenesis are affected by the level of dietary linoleate .