Skip to main content

Oxidative and excitatory mechanisms of developmental neurotoxicity: transcriptional profiles for chlorpyrifos, diazinon, dieldrin, and divalent nickel in PC12 cells.

Publication ,  Journal Article
Slotkin, TA; Seidler, FJ
Published in: Environ Health Perspect
April 2009

BACKGROUND: Oxidative stress and excitotoxicity underlie the developmental neurotoxicity of numerous chemicals. OBJECTIVES: We compared the effects of organophosphates (chlorpyrifos and diazinon), an organo-chlorine (dieldrin), and a metal [divalent nickel (Ni2+)] to determine how these mechanisms contribute to similar or dissimilar neurotoxic outcomes. METHODS: We used PC12 cells as a model of developing neurons and evaluated transcriptional profiles for genes for oxidative stress responses and glutamate receptors. RESULTS: Chlorpyrifos had a greater effect on oxidative-stress-related genes in differentiating cells compared with the undifferentiated state. Chlorpyrifos and diazinon showed significant concordance in their effects on glutathione-related genes, but they were negatively correlated for effects on catalase and superoxide dismutase isoforms and had no concordance for effects on ionotropic glutamate receptors. Surprisingly, the correlations were stronger between diazinon and dieldrin than between the two organophosphates. The effects of Ni2+ were the least similar for genes related to oxidative stress but had significant concordance with dieldrin for effects on glutamate receptors. CONCLUSIONS: Our results point to underlying mechanisms by which different organophosphates produce disparate neurotoxic outcomes despite their shared property as cholinesterase inhibitors. Further, apparently unrelated neurotoxicants may produce similar outcomes because of convergence on oxidative stress and excitotoxicity. The combined use of cell cultures and microarrays points to specific end points that can distinguish similarities and disparities in the effects of diverse developmental neurotoxicants.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Environ Health Perspect

DOI

EISSN

1552-9924

Publication Date

April 2009

Volume

117

Issue

4

Start / End Page

587 / 596

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Toxicology
  • Superoxide Dismutase
  • Receptors, Glutamate
  • Rats
  • PC12 Cells
  • Organothiophosphorus Compounds
  • Nickel
  • Neurons
  • Neurogenesis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Slotkin, T. A., & Seidler, F. J. (2009). Oxidative and excitatory mechanisms of developmental neurotoxicity: transcriptional profiles for chlorpyrifos, diazinon, dieldrin, and divalent nickel in PC12 cells. Environ Health Perspect, 117(4), 587–596. https://doi.org/10.1289/ehp.0800251
Slotkin, Theodore A., and Frederic J. Seidler. “Oxidative and excitatory mechanisms of developmental neurotoxicity: transcriptional profiles for chlorpyrifos, diazinon, dieldrin, and divalent nickel in PC12 cells.Environ Health Perspect 117, no. 4 (April 2009): 587–96. https://doi.org/10.1289/ehp.0800251.
Slotkin, Theodore A., and Frederic J. Seidler. “Oxidative and excitatory mechanisms of developmental neurotoxicity: transcriptional profiles for chlorpyrifos, diazinon, dieldrin, and divalent nickel in PC12 cells.Environ Health Perspect, vol. 117, no. 4, Apr. 2009, pp. 587–96. Pubmed, doi:10.1289/ehp.0800251.

Published In

Environ Health Perspect

DOI

EISSN

1552-9924

Publication Date

April 2009

Volume

117

Issue

4

Start / End Page

587 / 596

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Toxicology
  • Superoxide Dismutase
  • Receptors, Glutamate
  • Rats
  • PC12 Cells
  • Organothiophosphorus Compounds
  • Nickel
  • Neurons
  • Neurogenesis