BENZO [k]FLUORANTHENE ENHANCEMENT AND SUPPRESSION OF 17BETA-ESTRADIOL CATABOLISM IN MCF-7 BREAST CANCER CELLS

Abstract

It previously was shown that benzo[k]fluoranthene (BkF), a polycyclic aromatic hydrocarbon frequently detected in environmental samples, increases catabolism of 17 estradiol ( E₂) in human breast cancer cells. Data in the present paper demonstrate that BkF both increases and inhibits the catabolism of E₂ in MCF-7 breast cancer cells, and that the in vitro BkF increase and inhibition are dependent on the concentration of BkF and the length of the incubation period. A radiometric assay was used to investigate the catabolism of [³H]E₂ after exposure to 5 concentrations of BkF for 6, 12, 24, 36, 48, 60, or 72 h. The concentration of BkF necessary for maximal increase in catabolism of E₂ varied with the incubation period. At 6 h, a maximal increase was obtained with 0.01 and 0.1 muM, and at 48 h a maximal increase was obtained with 0.5 muM and 1 muM BkF. The increased rate of E₂ catabolism was transient at lower concentrations of BkF but remained maximal at 72 h with 0.5 and 1 mu MBkF. The highest concentration of BkF tested, 5 muM, was inhibitory at all time points. In contrast to BkF, fluoranthene (FL), another PAH frequently detected in environmental samples, did not significantly increase the catabolism of E₂ at any of the concentrations or time points tested. Results showing that BkF inhibits the catabolism of E₂ induced by 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD) suggest that the BkF inhibition of cellular E₂ catabolism is due to competition between BkF and E₂ for the TCDD-induced enzymes. Overall, results from these studies demonstrate that BkF both increases and inhibits the cellular catabolism of E₂, and emphasize the importance of considering time as well as concentration when conducting short-term in vitro assays.