Developmental neurotoxicity of different pesticides in PC-12 cells in vitro

Journal Article · Thu Jun 15 04:00:00 EDT 2017 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2017.03.027· OSTI ID:22690989

Christen, Verena ^[1]; Rusconi, Manuel; Crettaz, Pierre ^[2]; Fent, Karl ^[1]

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1. University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132, Muttenz (Switzerland)
2. Federal Office of Public Health, Division Chemical Products, 3003 Bern (Switzerland)

The detection of developmental neurotoxicity (DNT) of chemicals has high relevance for protection of human health. However, DNT of many pesticides is only little known. Furthermore, validated in vitro systems for assessment of DNT are not well established. Here we employed the rat phaeochromocytoma cell line PC-12 to evaluate DNT of 18 frequently used pesticides of different classes, including neonicotinoids, pyrethroids, organophosphates, organochlorines, as well as quaternary ammonium compounds, the organic compound used in pesticides, piperonyl butoxide, as well as the insect repellent diethyltoluamide (DEET). We determined the outgrowth of neurites in PC-12 cells co-treated with nerve growth factor and different concentrations of biocides for 5 days. Furthermore, we determined transcriptional alterations of selected genes that may be associated with DNT, such as camk2α and camk2β, gap-43, neurofilament-h, tubulin-α and tubulin-β. Strong and dose- dependent inhibition of neurite outgrowth was induced by azamethiphos and chlorpyrifos, and dieldrin and heptachlor, which was correlated with up-regulation of gap-43. No or only weak effects on neurite outgrowth and transcriptional alterations occurred for neonicotinoids acetamiprid, clothianidin, imidacloprid and thiamethoxam, the pyrethroids λ-cyhalothrin, cyfluthrin, deltamethrin, and permethrin, the biocidal disinfectants C12-C14-alkyl(ethylbenzyl)dimethylammonium (BAC), benzalkonium chloride and barquat (dimethyl benzyl ammonium chloride), and piperonyl butoxide and DEET. Our study confirms potential developmental neurotoxicity of some pesticides and provides first evidence that azamethiphos has the potential to act as a developmental neurotoxic compound. We also demonstrate that inhibition of neurite outgrowth and transcriptional alterations of gap-43 expression correlate, which suggests the employment of gap-43 expression as a biomarker for detection and initial evaluation of potential DNT of chemicals. - Highlights: • The developmental neurotoxicity (DNT) of biocides is poorly known. • We assessed different classes of biocides for DNT in PC-12 cells. • DNT was shown by neurite outgrowth (NOG) and transcriptional changes. • Azamethiphos, chlorpyrifos, dieldrin and heptachlor showed DNT. • NOG correlated with induction of gap-43 which is an important determinant for DNT.

• OSTI ID: 22690989
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Vol. 325; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ABUNDANCE
AMMONIUM CHLORIDES
BIOLOGICAL MARKERS
CARBON 12
CARBON 14
CONCENTRATION RATIO
DIELDRIN
DISINFECTANTS
GROWTH FACTORS
IN VITRO
INSECTS
ORGANIC CHLORINE COMPOUNDS
PUBLIC HEALTH
QUATERNARY AMMONIUM COMPOUNDS
RATS