Benzo[k]fluoranthene enhancement and suppression of 17β-estradiol catabolism in MCF-7 breast cancer cells

It previously was shown that benzo[k]fluoranthene (BkF), a polycyclic aromatic hydrocarbon frequently detected in environmental samples, increases catabolism of 17 beta-estradiol (E-2) in human breast cancer cells. Data in the present paper demonstrate that BkF both increases and inhibits the catabolism of E-2 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 [H-3]E-2 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 E-2 varied with the incubation period. At 6 h, a maximal increase was obtained with 0.01 and 0. 1 mu M, and at 48 h a maximal increase was obtained with 0.5 mu M and 1 mu M BkF. The increased rate of E-2 catabolism was transient at lower concentrations of BkF but remained maximal at 72 h with 0.5 and 1 mu M BkF. The highest concentration of BkF tested, 5 mu M, was inhibitory at ail time points. In contrast to BkF, fluoranthene (FL), another PAH frequently detected in environmental samples, did not significantly increase the catabolism of E-2 at any of the concentrations or time points tested. Results showing that BkF inhibits the catabolism of E-2 induced by 2,3,7,8-tetrachiorodibenzo-p-dioxin (TCDD) suggest that the BkF inhibition of cellular E-2 catabolism is due to competition between BkF and E-2 for the TCDD-induced enzymes. Overall, results from these studies demonstrate that BkF both increases and inhibits the cellular catabolism of E-2, and emphasize the importance of considering time as well as concentration when conducting short-term in vitro assays.