Beta-carotene inhibition of 7,12-dimethylbenz[a]anthracene-induced transformation of murine mammary cells in vitro.

Abstract

The chemopreventive action of beta-carotene during chemically-induced transformation of the epithelial cells in organ culture of the whole mammary glands from BALB/c female mice was studied. The mammary epithelial cells in the whole mammary organ in a hormone supplemented, serum-free medium were transformed after 24 h exposure to 7.8 microM 7,12-dimethylbenz[a]anthracene (DMBA) between 3rd and 4th day of a total 10 day culture period. The transformation process was associated with appearance of nodule-like alveolar lesions (NLAL) in glands in vitro. The epithelial cells transformed by DMBA are potentially neoplastic, and NLAL serves as a morphological marker of preneoplasia in the glands in vitro. Treatment with beta-carotene (10(-6) M) during DMBA exposure (3rd-4th day) caused 68% inhibition in the number of glands with incidence of NLAL. A 49% inhibition of NLAL was evident when the glands were incubated with beta-carotene (days 4-10) after exposure to DMBA. Results indicate that beta-carotene inhibits DMBA-induced transformation of the mammary glands in vitro acting both at the initiation and the promotional stages. This inhibitory effect is likely due to the action of beta-carotene itself since no accumulation of retinol, the metabolic derivative of the vitamin A precursor, was detectable in the mammary glands during the 10 day culture period.