title: Organophosphorus pesticide chlorpyrifos and its metabolites alter the expression of biomarker genes of differentiation in D3 mouse embryonic stem cells in a comparable way to other model neurodevelopmental toxicants.
abstract: There are discrepancies about whether chlorpyrifos is able to induce neurodevelopmental toxicity or not. We previously reported alterations in the pattern of expression of biomarker genes of differentiation in D3 mouse embryonic stem cells caused by chlorpyrifos and its metabolites chlorpyrifos-oxon and 3,5,6-trichloro-2-pyridinol. Now, we reanalyze these data comparing the effects on these genes with those caused in the same genes by retinoic acid, valproic acid, and penicillin-G (model compounds considered as strong, weak, and non-neurodevelopmental toxicants, respectively). We also compare the effects of chlorpyrifos and its metabolites on the cell viability of D3 cells and 3T3 mouse fibroblasts with the effects caused in the same cells by the three model compounds. We conclude that chlorpyrifos and its metabolites act, regarding these end-points, as the weak neurodevelopmental toxicant valproic acid, and consequently, a principle of caution should be applied avoiding occupational exposures in pregnant women. A second independent experiment run with different cellular batches coming from the same clone obtained the same result as the first one.
authors.affiliation: Unidad de Toxicología y Seguridad Química, Instituto de Bioingeniería, Universidad Miguel Hernández de Elche , Avenida de la Universidad s/n, 03202-Elche, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Estevan
authors.forename: Encarnación
authors.initials: E
authors.lastname: Fuster
authors.forename: Eva
authors.initials: E
authors.lastname: Del Río
authors.forename: David
authors.initials: D
authors.lastname: Pamies
authors.forename: Eugenio
authors.initials: E
authors.lastname: Vilanova
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sogorb
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004390:Chlorpyrifos / Q000378:metabolism / Q000633:toxicity*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D055495:Neurogenesis / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000633:toxicity; D010400:Penicillin G / Q000633:toxicity; D010575:Pesticides / Q000633:toxicity*; D014212:Tretinoin / Q000633:toxicity; D014635:Valproic Acid / Q000633:toxicity
chemical_list: D015415:Biomarkers; D009943:Organophosphorus Compounds; D010575:Pesticides; D014212:Tretinoin; D014635:Valproic Acid; D004390:Chlorpyrifos; D010400:Penicillin G