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

Biochem Biophys Res Commun. 1997 Feb 3;231(1):117-20. doi: 10.1006/bbrc.1997.6053.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Benzo(a)pyrene / pharmacology*
  • Cell Division / drug effects
  • Choriocarcinoma
  • Cytochrome P-450 CYP1A1 / biosynthesis
  • ErbB Receptors / metabolism
  • Gene Expression Regulation / drug effects*
  • Genes, myc*
  • Humans
  • Polychlorinated Dibenzodioxins / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / genetics*
  • Trophoblasts / cytology
  • Trophoblasts / drug effects*
  • Trophoblasts / metabolism
  • Tumor Cells, Cultured

Substances

  • Polychlorinated Dibenzodioxins
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Benzo(a)pyrene
  • Cytochrome P-450 CYP1A1
  • ErbB Receptors