β-Carotene inhibition of 7,12-dimethylbenz[a]anthracene-induced transformation of murine mammary cells in vitro

Abstract

The chemopreventive action of β-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 μM 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 β-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 β-carotene (days 4–10) after exposure to DMBA. Results indicate that β-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 β-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.