Effect of organophosphorus insecticides and their metabolites on astroglial cell proliferation

Marina Guizzetti, Shantha Pathak, Gennaro Giordano, Lucio G. Costa

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Though little attention has been given to the possibility that glial cells may represent a target for the developmental neurotoxicity of organophosphorus (OP) insecticides, recent evidence, obtained in particular with chlorpyrifos (CP), suggests that developmental exposure to this compound may indeed target astrocytes. To substantiate and expand these observations, we carried out a series of in vitro studies utilizing fetal rat astrocytes and a human astrocytoma cell line, 1321N1 cells, to investigate the effect of the OPs CP, diazinon (DZ) and parathion (P), their oxygen analogs chlorpyrifos oxon (CPO), diazoxon (DZO) and paraoxon (PO), and their metabolites 3,5,6-trichloro-2- pyridinol (TCP), 2-isopropyl-6-methyl-4-pyrimidol (IMP) and para-nitrophenol (PNP), on cell proliferation. In fetal rat astrocytes and astrocytoma cells maintained in serum, CP, DZ, P, CPO, DZO, and PO induced a concentration- dependent inhibition in [3H]thymidine incorporation with a very similar potency (IC50 between 45 and 57 μM). Among the other metabolites, PNP was the most potent (IC50 = 70-80 μM), while TCP and IMP were much less effective (IC50 > 100 μM). Cytotoxicity appears to account only for a small part of the effect on DNA synthesis. OP insecticides and their oxons were three- to six-fold more potent in inhibiting [3H]thymidine incorporation when cells were synchronized in the G0/G1 phase of the cell cycle and re-stimulated by carbachol or epidermal growth factor. These results suggest that OP insecticides and their oxons affect astroglial cell proliferation and that the transition from the G0/G1 to the S/G2 phase of the cell cycle may be particularly sensitive to the action of these compounds.

Original languageEnglish (US)
Pages (from-to)182-190
Number of pages9
Issue number3
StatePublished - Nov 15 2005
Externally publishedYes


  • Astroglial cells
  • Cell proliferation
  • Developmental neurotoxicity
  • Organophosphorus insecticides

ASJC Scopus subject areas

  • Toxicology


Dive into the research topics of 'Effect of organophosphorus insecticides and their metabolites on astroglial cell proliferation'. Together they form a unique fingerprint.

Cite this