Open access
Research Article
1 September 2001

Developmental neurotoxicity of chlorpyrifos modeled in vitro: comparative effects of metabolites and other cholinesterase inhibitors on DNA synthesis in PC12 and C6 cells.

Publication: Environmental Health Perspectives
Volume 109, Issue 9
Pages 909 - 913

Abstract

The widely used organophosphate pesticide chlorpyrifos is a suspected neuroteratogen. In the current study, we compared the effects of chlorpyrifos and its major metabolites in two in vitro models, neuronotypic PC12 cells and gliotypic C6 cells. Chlorpyrifos inhibited DNA synthesis in both cell lines but had a greater effect on gliotypic cells. Chlorpyrifos oxon, the active metabolite that inhibits cholinesterase, also decreased DNA synthesis in PC12 and C6 cells with a preferential effect on the latter. Trichloropyridinol, the major catabolic product of chlorpyrifos, had a much smaller, but nevertheless statistically significant, effect that was equivalent in both cell lines. Diazinon, another organophosphate pesticide, also inhibited DNA synthesis with preference toward C6 cells, but was less effective than was chlorpyrifos. Physostigmine, a non-organophosphate cholinesterase inhibitor, was less effective than either chlorpyrifos or diazinon, but still caused significant inhibition of DNA synthesis in C6 cells. We also found that the addition of sera protected the cells from the adverse effects of chlorpyrifos and that the effect could be reproduced by addition of albumin. These results indicate that chlorpyrifos and other organophosphates such as diazinon have immediate, direct effects on neural cell replication, preferentially for gliotypic cells. In light of the protective effect of serum proteins, the fact that the fetus and newborn possess lower concentrations of these proteins suggests that greater neurotoxic effects may occur at blood levels of chlorpyrifos that are nontoxic to adults.

Formats available

You can view the full content in the following formats:

Information & Authors

Information

Published In

Environmental Health Perspectives
Volume 109Issue 9September 2001
Pages: 909 - 913
PubMed: 11673119

History

Published online: 1 September 2001

Authors

Affiliations

D Qiao
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
F J Seidler
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
T A Slotkin
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.

Metrics & Citations

Metrics

About Article Metrics


Citations

Download citation

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click DOWNLOAD.

Cited by

  • Combined light and electron microscopy (CLEM) to quantify methamphetamine-induced alpha-synuclein-related pathology, Journal of Neural Transmission, 10.1007/s00702-024-02741-x, (2024).
  • Bacopa Protects against Neurotoxicity Induced by MPP+ and Methamphetamine, Molecules, 10.3390/molecules27165204, 27, 16, (5204), (2022).
  • Organophosphate Insecticide Toxicity in Neural Development, Cognition, Behaviour and Degeneration: Insights from Zebrafish, Journal of Developmental Biology, 10.3390/jdb10040049, 10, 4, (49), (2022).
  • Alterations of Mitochondrial Structure in Methamphetamine Toxicity, International Journal of Molecular Sciences, 10.3390/ijms23168926, 23, 16, (8926), (2022).
  • Medicinal herbs and multiple sclerosis: Overview on the hard balance between new therapeutic strategy and occupational health risk, Frontiers in Cellular Neuroscience, 10.3389/fncel.2022.985943, 16, (2022).
  • Neuronal differentiation pathways and compound-induced developmental neurotoxicity in the human neural progenitor cell test (hNPT) revealed by RNA-seq, Chemosphere, 10.1016/j.chemosphere.2022.135298, 304, (135298), (2022).
  • Cell signaling mechanisms in developmental neurotoxicity, Reproductive and Developmental Toxicology, 10.1016/B978-0-323-89773-0.00055-2, (1117-1127), (2022).
  • Pesticide safety in livestock products, Managing Healthy Livestock Production and Consumption, 10.1016/B978-0-12-823019-0.00007-6, (73-91), (2022).
  • Lactoferrin Protects against Methamphetamine Toxicity by Modulating Autophagy and Mitochondrial Status, Nutrients, 10.3390/nu13103356, 13, 10, (3356), (2021).
  • Norepinephrine Protects against Methamphetamine Toxicity through β2-Adrenergic Receptors Promoting LC3 Compartmentalization, International Journal of Molecular Sciences, 10.3390/ijms22137232, 22, 13, (7232), (2021).

View Options

View options

PDF

View PDF

Get Access

Restore your content access

Enter your email address to restore your content access:

Note: This functionality works only for purchases done as a guest. If you already have an account, log in to access the content to which you are entitled.

Media

Figures

Other

Tables

Share

Share

Copy the content Link

Share on social media