Benzo[k]fluoranthene enhancement and suppression of 17beta-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 17beta 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 microM, and at 48 h a maximal increase was obtained with 0.5 microM and 1 microM 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 microM BkF. The highest concentration of BkF tested, 5 microM, 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.
Arcaro
K F
KF
School of Public Health, State University of New York at Albany, Wadsworth Center, New York State Department of Health, 12201, USA. arcaro@wadsworth.org
Yang
Y
Y
Gierthy
J F
JF
D001943:Breast Neoplasms / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000494:pharmacology*; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D005449:Fluorenes / Q000494:pharmacology*; D006801:Humans; D013997:Time Factors; D014407:Tumor Cells, Cultured
D004785:Environmental Pollutants; D005449:Fluorenes; D004958:Estradiol; C022921:benzo(k)fluoranthene