Modulation by benzo[ a]pyrene of epidermal growth factor receptors, cell proliferation, and secretion of human chorionic gonadotropin in human placental cell lines

Abstract

Clinical observations indicate that maternal cigarette smoking has significant detrimental effects on fetoplacental development. The present study used human trophoblastic choriocarcinoma cell lines of placental origin to investigate the effects of benzo[ a]pyrene (BaP) on epidermal growth factor (EGF) receptors, cell proliferation and human chorionic gonadotropin (hCG) secretion. BaP decreased 125I-EGF binding and EGF receptor protein in a concentration-related manner in both BeWo and JEG-3 cell lines. The steady-state level of EGF receptor mRNA, however, was not changed significantly by BaP in either cell line. Cell proliferation was unchanged or slightly increased following exposure to 10 and 50 μM BaP in the presence of serum, whereas proliferation progressively decreased in cells exposed under serum-free conditions. The mitogenic effect of EGF was inhibited by cotreatment with BaP in both cell lines. Further study of trophoblast endocrine function showed that both basal and EGF-stimulated secretion of hCG was reduced significantly by BaP exposure in BeWo cells, whereas no adverse effect was seen in JEG-3 cells. Finally, cytochrome P450 1A1 (CYP1A1) was induced in a concentration-dependent manner by BaP in both cell lines. Thus, data indicate that the BaP-mediated loss of EGF receptors alters trophoblast proliferation and endocrine function, and that different mechanisms may be involved in the regulation of hCG secretion in BeWo and JEG-3 cells. In addition, this study supports the feasibility of using the BeWo and JEG-3 trophoblastic choriocarcinoma cell lines to investigate biomarkers and mechanisms of placental toxicity.