Effects of benzo-a-pyrene on oxytocin-induced Ca2+ oscillations in myometrial cells

Toxicol Lett. 2006 Aug 20;165(2):133-41. doi: 10.1016/j.toxlet.2006.02.005. Epub 2006 Mar 29.


Benzo-a-pyrene (BaP) is a polycyclic aromatic hydrocarbon that exists as a major environmental pollutant. The effect of this carcinogen/mutagen upon myometrial Ca(2+) signaling in a human myometrial cell line (PHM1) was examined. Exposure of cells to BaP did not alter basal Ca(2+) levels or the inositol(1,4,5) trisphosphate-releasable Ca(2+) pool. However, BaP significantly decreased the initial oxytocin-induced Ca(2+) transient and the frequency of oxytocin-induced Ca(2+)oscillations as well as delayed their onset. To determine the specific effects of BaP, pharmacologic agents that target intracellular Ca(2+) homeostasis mechanisms were used. Genistein (a non-specific tyrosine kinase inhibitor) and AG1478 (an epidermal growth factor receptor blocker) markedly reduced the oxytocin-induced Ca(2+) oscillations in control, but had no effect in BaP treated cells. Addition of epidermal growth factor or serum before or after oxytocin restored the Ca(2+) oscillations in BaP treated cells to a level similar to control cells, while the K(+) channel blocker tetraethylammonium chloride, partially restored the Ca(2+) response. These data suggest that the tyrosine kinase pathway, which is part of the G-protein coupled receptor pathway response to oxytocin in PHM1 cells, is a target of BaP action and that EGF or serum can restore the oxytocin-induced Ca(2+) oscillations.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Benzo(a)pyrene / toxicity*
  • Calcium / metabolism*
  • Calcium Signaling / drug effects*
  • Calcium Signaling / physiology
  • Carcinogens, Environmental / toxicity*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Drug Antagonism
  • Drug Combinations
  • Enzyme Inhibitors / pharmacology
  • Epidermal Growth Factor / pharmacology
  • Female
  • Genistein / pharmacology
  • Humans
  • Myometrium / drug effects*
  • Myometrium / metabolism
  • Myometrium / pathology
  • Oxytocin / pharmacology*
  • Pregnancy
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Quinazolines
  • Tetraethylammonium / pharmacology
  • Tyrphostins / pharmacology


  • Carcinogens, Environmental
  • Drug Combinations
  • Enzyme Inhibitors
  • Quinazolines
  • Tyrphostins
  • RTKI cpd
  • Benzo(a)pyrene
  • Oxytocin
  • Epidermal Growth Factor
  • Tetraethylammonium
  • Genistein
  • Protein-Tyrosine Kinases
  • Calcium