Correlation between retinoid inhibition of N-methyl-N-nitrosourea-induced mammary carcinogenesis and levels of retinoic acid binding proteins.
A correlation was made between the ability of retinoids to suppress N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis and the levels of cytosolic retinoic acid binding proteins (cRABP) in the cytosol of MNU-induced mammary tumors. Although retinyl acetate and N-(4-hydroxyphenyl)-retinamide were found to be effective inhibitors of mammary carcinogenesis in intact hosts, both retinoids were significantly more active in ovariectomized rats than in intact animals. Quantitative analysis of cRABP in the tumors indicated that mammary cancers arising in animals which were ovariectomized one week after MNU administration contained significantly increased concentrations of cRABP compared to cancers appearing in intact rats. In addition, when animals bearing palpable mammary tumors were ovariectomized, the tumors which continued to grow contained significantly higher levels of cRABP than did tumors which stopped growing or regressed. These data suggest that the selective inhibition of ovarian hormone-independent mammary cancer by retinyl acetate and N-(4-hydroxyphenyl)retinamide may be mediated through an increased level of cRABP in tumor cells of ovariectomized hosts.