Increasing levels of dietary
corn oil have been correlated with inhibition of 12-O-tetradecanoylphorbol-13-acetate-(TPA) promoted skin
tumorigenesis in mice (Leyton et al.
Cancer Res. 51, 907-915, 1991). This study was undertaken to assess the effects of dietary
corn oil on several events associated with
tumor promotion. Three semipurified diets containing 15% (wt/wt) total fat with increasing levels of
linoleate (0.8%, 4.5%, and 8.4%) supplied by
corn oil were fed to mice for at least four weeks. Although incorporation of
linoleate into epidermal
phosphatidylcholine increased with increasing amounts of dietary
corn oil, the elongated desaturated product of
linoleate, arachidonate, was similar or decreased slightly in mice fed the three diets. Minimal activity of delta 6-desaturase, the rate-limiting
enzyme in the conversion of
linoleate to
arachidonic acid, was found in the epidermis compared with the liver, suggesting that
linoleate is not converted to
arachidonic acid in the skin. Subcellular distribution of
protein kinase C was altered in mice fed 0.8%
linoleate, where 69% of
protein kinase C activity was in the cytosol compared with 78% and 74% for groups fed 4.5% and 8.4%
linoleate, respectively. Activation of partially purified
protein kinase C isolated from mouse epidermis by
linoleate was significantly lower (p < 0.01) than that isolated by
arachidonic acid. TPA-induced vascular permeability was significantly greater (p < 0.05), whereas
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 associated with
carcinogenesis are affected by the level of dietary
linoleate.