Document Detail

Chlorpyrifos developmental neurotoxicity: interaction with glucocorticoids in PC12 cells.
MedLine Citation:
PMID:  22796634     Owner:  NLM     Status:  MEDLINE    
Prenatal coexposures to glucocorticoids and organophosphate pesticides are widespread. Glucocorticoids are elevated by maternal stress and are commonly given in preterm labor; organophosphate exposures are virtually ubiquitous. We used PC12 cells undergoing neurodifferentiation in order to assess whether dexamethasone enhances the developmental neurotoxicity of chlorpyrifos, focusing on models relevant to human exposures. By themselves, each agent reduced the number of cells and the combined exposure elicited a correspondingly greater effect than with either agent alone. There was no general cytotoxicity, as cell growth was actually enhanced, and again, the combined treatment evoked greater cellular hypertrophy than with the individual compounds. The effects on neurodifferentiation were more complex. Chlorpyrifos alone had a promotional effect on neuritogenesis whereas dexamethasone impaired it; combined treatment showed an overall impairment greater than that seen with dexamethasone alone. The effect of chlorpyrifos on differentiation into specific neurotransmitter phenotypes was shifted by dexamethasone. Either agent alone promoted differentiation into the dopaminergic phenotype at the expense of the cholinergic phenotype. However, in dexamethasone-primed cells, chlorpyrifos actually enhanced cholinergic neurodifferentiation instead of suppressing this phenotype. Our results indicate that developmental exposure to glucocorticoids, either in the context of stress or the therapy of preterm labor, could enhance the developmental neurotoxicity of organophosphates and potentially of other neurotoxicants, as well as producing neurobehavioral outcomes distinct from those seen with either individual agent.
Theodore A Slotkin; Jennifer Card; Frederic J Seidler
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-07-14
Journal Detail:
Title:  Neurotoxicology and teratology     Volume:  34     ISSN:  1872-9738     ISO Abbreviation:  Neurotoxicol Teratol     Publication Date:    2012 Sep-Oct
Date Detail:
Created Date:  2012-10-01     Completed Date:  2013-02-25     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  8709538     Medline TA:  Neurotoxicol Teratol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  505-12     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC, USA.
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MeSH Terms
Cell Culture Techniques
Chlorpyrifos / toxicity*
Drug Interactions
Glucocorticoids / metabolism,  toxicity*
Insecticides / toxicity*
Models, Biological
Neurogenesis / drug effects*
Neurotoxicity Syndromes / etiology*,  metabolism,  pathology
PC12 Cells
Prenatal Exposure Delayed Effects / chemically induced*,  metabolism,  pathology
Grant Support
Reg. No./Substance:
0/Glucocorticoids; 0/Insecticides; 2921-88-2/Chlorpyrifos

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