Effects of dietary retinoic acid on skin papilloma and carcinoma formation in female SENCAR mice

Abstract

Previously we have shown that dietary retinoids are essential for papilloma formation induced by either an initiation-promotion or a complete skin carcinogenesis protocol. The present study was conducted to further determine the effect of dietary retinoic acid (RA) on papilloma formation and the conversion of papillomas to carcinomas. Skin tumors were induced in 3 week old female SENCAR mice by an initiation-promotion protocol with one application of 20 μg of 7,12-dimethylbenz[a]anthracene (DMBA), followed by 20 weekly applications of 2 μg of 12-O-tetradecanoylphorbol-13-acetate (TPA). Mice were fed RA at one of the three doses: 0.3 (nutritionally marginal dose), 3 (near physiological) and 30 (pharmacological) μg/g of diet. Mice fed 30 μg of RA/g of diet had the same survival rate as the other two groups despite a lower body weight and all three groups had similar papilloma incidence, which reached 100% at age 18 weeks. Mice fed 3 μg of RA/g of diet had the highest papilloma yield (∼14 papillomas/mouse) of all groups and it peaked between weeks 18 and 38 of age. These papillomas later regressed such that mice from all three groups had about the same papilloma yield at week 44 of age. Mice fed 30 μg of RA/g of diet failed to develop any visible carcinoma, while mice fed 0.3 or 3 μg/g showed 1.9% conversion of papillomas to carcinomas. Therefore, dietary RA at 30 μg/g of diet inhibited the conversion of papillomas to carcinomas without affecting papilloma incidence. In addition, dietary RA at 30 and 0.3 μg/g of diet lowered papilloma yield.