DIETARY ENERGY AND FAT EFFECTS ON TUMOR PROMOTION

We investigated dietary modulation, by energy level and energy source, of two-stage skin tumorigenesis initiated with 7,12-dimethyl-benz(a)a nthracene and promoted with 12-O-tetradecanoylphorbol-13-acetate in SE NCAR mice. Studies comparing the influence of dietary calorie restrict ion (feeding less carbohydrate and less fat) with diet restriction and with ad libitum control feeding indicated an inhibition of papillomas and carcinomas in both restricted groups. The inhibition was greatest in the calorie-restricted group. We reported an increase in the numbe r and incidence of papillomas and the earlier appearance of carcinomas in mice fed a high-fat diet during promotion, in comparison with cont rol groups fed the same calorie allotment. Recent work compared restri ction of fat calories (high carbohydrate, restricted fat) with restric tion of carbohydrate calories (high fat, restricted carbohydrate), and both protocols resulted in fewer papillomas and carcinomas. Restricti on of fat calories resulted in a greater inhibition of papillomas, whe reas carcinoma rates were comparable with both protocols. Protein kina se C activity in epidermal cells from mice fed the high-fat diet was h igher than activity from mice fed the control diet. Calorie restrictio n reduced protein kinase C activity. Phosphatidylinositol-inositol pho sphate labeling studies suggest alteration of inositol lipid turnover in epidermal cells from mice fed a calorie-restricted diet.