Deregulation of Cell Proliferation by Polycyclic Aromatic Hydrocarbons in Human Breast Carcinoma MCF-7 Cells Reflects Both Genotoxic and Nongenotoxic Events

Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]-pyrene (BaP), are carcinogens suggested to be involved in develop-ment of human cancer. Several recent studies have reported that PAHs can activate estrogen receptors (ER), either directly or indir-ectly by producing estrogenicmetabolites.Wehypothesized that the activation of ER by PAHs or their metabolites could induce cell proliferation in estrogen-sensitive cells. In the present study, we found that two PAHs, benz[a]anthracene (BaA) and BaP, can stimulate proliferation of human breast carcinoma MCF-7 cells at concentrations 100 nM and higher. This effect was ER-dependent, because it was blocked by the pure antiestrogen ICI 182,780. Although both PAHs partially inhibited S-phase entry and DNA synthesis induced by 17b-estradiol, they stimulated S-phase entry when applied to MCF-7 cells synchronized by serum deprivation. This was in contrast with model antiestrogenic ary