HIGH DIETARY RETINOIC ACID INHIBITS TUMOR PROMOTION AND MALIGNANT CONVERSION IN A 2-STAGE SKIN CARCINOGENESIS PROTOCOL USING 7,12-DIMETHYLBENZ[ALPHA]ANTHRACENE AS THE INITIATOR AND MEZEREIN AS THE TUMOR PROMOTER IN FEMALE SENCAR MICE

We studied the effect of dietary retinoic acid (RA) in a two-stage protocol of skin carcinogenesis in female SENCAR mice, At 3 weeks of age mice were initiated with 7,12-dimethylbenz[a]anthracene (DMBA, 20 mu g) and promoted with either 12-O-tetradecanoylphsrbol-13-acetate (TPA, 2 mu g) once per week or mezerein (MEZ, 4 mu g) twice per week for 20 weeks, At the week of DMBA initiation mice were also put on a purified diet containing either 3 (physiological dose) or 30 mu g (pharmacological dose) of RA/g of diet. High dietary RA significantly inhibited papilloma yield but not incidence in the MEZ-promoted group. Papilloma incidence and yield were also lower in the MEZ- than in the TPA-treated groups. Cumulative carcinoma incidence and yield, and conversion efficiency (= (carcinomas/maximal papillomas) x 100%), were all decreased by high dietary RA in both MEZ- and TPA-treated groups. These results demonstrate that high dietary RA inhibited skin carcinogenesis in MEZ-promoted mice at the stages of tumor promotion and malignant conversion, while this inhibition occurred only at the malignant conversion stage in TPA-promoted mice.