Differential effects of dietary beta-carotene on papilloma and carcinoma formation induced by an initiation-promotion protocol in SENCAR mouse skin.

SENCAR mice were used to determine the effects of the provitamin A compound beta-carotene on papilloma formation and the conversion of papillomas to carcinomas in a two-stage protocol with one application of the initiator 7,12-dimethylbenz[a]anthracene (DMBA, 20 micrograms) and 20 weekly applications of the promotor 12-O-tetradecanoylphorbol-13-acetate (TPA, 2 micrograms). A purified vitamin A-free diet was supplemented with beta-carotene at four levels (0.6, 6, 60 and 600 micrograms/g of diet) for female mice and two levels (60 and 600 micrograms/g) for male mice. Dietary supplementations of beta-carotene did not result in significant changes in body weight and survival of female and male mice. However, papillomas developed more rapidly and papilloma incidence (% mice with papillomas) reached its maximum (100%) sooner in male mice fed 600 micrograms of beta-carotene/g of diet than those fed 60 micrograms/g. There were smaller differences in papilloma incidence among the dietary groups in female mice, but the papilloma incidence again reached 100% sooner in mice fed 600 micrograms of beta-carotene/g of diet. Female and male mice fed 600 micrograms of beta-carotene/g of diet had significantly higher papilloma yields (average number of papillomas/mouse) than other dietary groups and a very low percentage of these papillomas converted to carcinomas in these mice. Thus, beta-carotene at 600 micrograms/g inhibited the conversion of papillomas to carcinomas in both sexes. In addition, papilloma yields were higher in female mice and these papillomas regressed more quickly than those in the corresponding groups of male mice. In conclusion, dietary beta-carotene caused differential effects on papilloma and carcinoma yields and sex-dependent differences in papilloma formation in female and male SENCAR mice treated with DMBA and TPA in a two-stage carcinogenesis protocol.