Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

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

Authors: Slotkin, Theodore A; Seidler, Frederic J

Published In Environ Health Perspect, (2009 Apr)

Abstract: 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.

PubMed ID: 19440498 Exiting the NIEHS site

MeSH Terms: Animals; Catalase/metabolism; Cations, Divalent/toxicity; Cell Differentiation; Chlorpyrifos/toxicity; Diazinon/toxicity; Dieldrin/toxicity*; Gene Expression Profiling; Gene Expression Regulation, Developmental/drug effects; Glutathione Transferase/metabolism; Insecticides/toxicity*; Neurogenesis/drug effects; Neurons/drug effects*; Nickel/toxicity*; Organothiophosphorus Compounds/toxicity*; PC12 Cells; Rats; Receptors, Glutamate/metabolism; Superoxide Dismutase/metabolism; Transcription, Genetic/drug effects

Back
to Top