ENHANCEMENT OF BENZO(A)PYRENE METABOLISM MEDIATED BY RETINOL ACETATE IN CULTURED HUMAN BRONCHIAL EPITHELIAL-CELLS

As suggested by animal studies and human epidemiological data, retinoids possess significant cancer chemopreventive activity. Although the majority of studies in this area have focused on the ability of retinoids to prevent the promotion or progression of carcinogenesis, a significant amount of data suggest retinoids can alter initiation events. In the current report, we have evaluated the potential of retinol acetate to modulate benzo(a)pyrene metabolism in low-passage human bronchial epithelial cells in monolayer cultures, Of 16 different cell cultures, benzo(a)pyrene metabolism was increased in 14, decreased in one, and unchanged in one, when retinol acetate was added to the media, In a preliminary study with one of the cell cultures in which retinol acetate significantly enhanced benzo(a)pyrene metabolism, binding of carcinogen metabolites to;DNA was unaffected, Since retinoids are known cancer chemopreventive agents and carcinogen binding to DNA is the key event in the initiation of carcinogenesis, these results suggest that retinoids may decrease carcinogenic risk by increasing the detoxification of procarcinogens such as benzo(a)pyrene ina manner that does not yield a concomitant increase in damage to critical cellular targets such as DNA.