High dietary retinoic acid inhibits tumor promotion and malignant conversion in a two-stage skin carcinogenesis protocol using 7,12-dimethylbenz[a]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 μg) and promoted with either 12-O-tetradecanoylphorbol-13-acetate (TPA, 2μg) once per week or mezerein (MEZ, 4μg) 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 μg (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) × 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.