Benzo(a)pyrene, but not 2,3,7,8-tetrachlorodibenzo-p-dioxin, alters cell proliferation and c-myc and growth factor expression in human placental choriocarcinoma JEG-3 cells.
This study compared the effects of benzo(a)pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), two aryl hydrocarbon receptor (AhR) agonists, on proliferation and gene expression in the human placental choriocarcinoma JEG-3 cell line. BaP significantly inhibited [3H]thymidine incorporation, whereas no effect of TCDD was observed over a 7 day period. TCDD and BaP both showed induction of cytochrome P450 1A1 (CYP1A1), whereas only BaP caused a significant loss of EGFRs. Exposure to 10 microM BaP significantly increased the steady state mRNA level of transforming growth factor (TGF)-beta 1, while the c-myc mRNA levels were decreased by 61%. In contrast, TCDD showed no changes in mRNA levels for TGF-beta 1 and c-myc. Thus, although both compounds induce CYP1A1, only BaP inhibits cell proliferation which is correlated with disruption of expression of significant regulators of trophoblast growth.
Zhang
L
L
Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville 32610-0267, USA.
Shiverick
K T
KT
D001564:Benzo(a)pyrene / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002822:Choriocarcinoma; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D066246:ErbB Receptors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D016259:Genes, myc; D006801:Humans; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics*; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D001564:Benzo(a)pyrene; D019363:Cytochrome P-450 CYP1A1; D066246:ErbB Receptors