Retinoid Prevents Mammary Gland Transformation by Carcinogenic Hydrocarbon in Whole-Organ Culture

The mouse mammary gland in whole-organ culture, an in vitro system that is capable of alveolar development, differentiation, involution, and oncogenic transformation, has been used to examine the effects of the retinoid 2-retinylidene-5,5-dimethyl-1,3-cyclohexanedione (retinylidene dimedone) on epithelial transformation by a low concentration (10 nM) of the carcinogen 7,12-dimethylbenz[a]anthracene. The retinoid significantly prevented mammary gland transformation only when administered after the carcinogen. In addition, the phenotypes of the early transformed state of the mammary gland were suppressed for 20 days after removal of the retinoid. The retinoid was effective during both mammary alveolar development and regression in culture at concentrations as low as 1 nM, and itself had no significant transforming or cytotoxic activity. Mammary glands treated with both the carcinogen and the retinoid resembled, at the microscopic level, those given the solvent (dimethyl sulfoxide) only. The mouse mammary gland in whole-organ culture provides a promising model system in which to study the actions by which retinoids prevent and suppress the chemical transformation in vitro and oncogenesis in vivo of epithelial cells in general and of mammary gland in particular. The present findings support the suggestion that a search for suitable retinoids as chemopreventive agents against human breast cancer is warranted. This model system may be useful as an initial indicator in that search.