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dc.contributor.authorChristen, Verena
dc.contributor.authorFent, Karl
dc.contributor.authorRusconi, Manuel
dc.contributor.authorCrettaz, Pierre
dc.date.accessioned2018-01-10T09:36:54Z
dc.date.available2018-01-10T09:36:54Z
dc.date.issued2017
dc.identifier.doi10.1016/j.taap.2017.03.027
dc.identifier.urihttp://hdl.handle.net/11654/25802
dc.description.abstractThe 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.
dc.language.isoen_US
dc.relation.ispartofToxicology and Applied Pharmacology
dc.accessRightsAnonymous
dc.subjectDevelopmental neurotoxicity
dc.subjectPC-12 cells
dc.subjectNeurite outgrowth
dc.subjectNeonicotinoids
dc.subjectBiocides
dc.subjectPesticides
dc.titleDevelopmental neurotoxicity of different pesticides in PC-12 cells in vitro
dc.type01 - Zeitschriftenartikel, Journalartikel oder Magazin
dc.volume325
dc.audienceScience
fhnw.publicationStatePublished
fhnw.ReviewTypeAnonymous ex ante peer review of a complete publication
fhnw.InventedHereYes
fhnw.PublishedSwitzerlandYes
fhnw.pagination25-36
fhnw.IsStudentsWorkno
fhnw.publicationOnlineJa


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