title: Differential epigenetic effects of chlorpyrifos and arsenic in proliferating and differentiating human neural progenitor cells.
abstract: Understanding the underlying temporal and mechanistic responses to neurotoxicant exposures during sensitive periods of neuronal development are critical for assessing the impact of these exposures on developmental processes. To investigate the importance of timing of neurotoxicant exposure for perturbation of epigenetic regulation, we exposed human neuronal progenitor cells (hNPCs) to chlorpyrifos (CP) and sodium arsenite (As; positive control) during proliferation and differentiation. CP or As treatment effects on hNPCs morphology, cell viability, and changes in protein expression levels of neural differentiation and cell stress markers, and histone H3 modifications were examined. Cell viability, proliferation/differentiation status, and epigenetic results suggest that hNPCs cultures respond to CP and As treatment with different degrees of sensitivity. Histone modifications, as measured by changes in histone H3 phosphorylation, acetylation and methylation, varied for each toxicant and growth condition, suggesting that differentiation status can influence the epigenetic effects of CP and As exposures.
authors: Department of Environmental and Occupational Health, Institute of Risk Analysis and Risk Communication, University of Washington, 4225 Roosevelt Way NE, Seattle, WA, United States.
authors: Hee Yeon
authors: HY
authors: Kim
authors: Department of Environmental and Occupational Health, Institute of Risk Analysis and Risk Communication, University of Washington, 4225 Roosevelt Way NE, Seattle, WA, United States.
authors: Susanna H
authors: SH
authors: Wegner
authors: Department of Environmental and Occupational Health, Institute of Risk Analysis and Risk Communication, University of Washington, 4225 Roosevelt Way NE, Seattle, WA, United States.
authors: Kirk P
authors: KP
authors: Van Ness
authors: Department of Environmental and Occupational Health, Institute of Risk Analysis and Risk Communication, University of Washington, 4225 Roosevelt Way NE, Seattle, WA, United States.
authors: Julie Juyoung
authors: JJ
authors: Park
authors: Department of Environmental and Occupational Health, Institute of Risk Analysis and Risk Communication, University of Washington, 4225 Roosevelt Way NE, Seattle, WA, United States.
authors: Sara E
authors: SE
authors: Pacheco
authors: Department of Environmental and Occupational Health, Institute of Risk Analysis and Risk Communication, University of Washington, 4225 Roosevelt Way NE, Seattle, WA, United States.
authors: Tomomi
authors: T
authors: Workman
authors: Department of Environmental and Occupational Health, Institute of Risk Analysis and Risk Communication, University of Washington, 4225 Roosevelt Way NE, Seattle, WA, United States.
authors: Sungwoo
authors: S
authors: Hong
authors: Department of Environmental and Occupational Health, Institute of Risk Analysis and Risk Communication, University of Washington, 4225 Roosevelt Way NE, Seattle, WA, United States.
authors: William
authors: W
authors: Griffith
authors: Department of Environmental and Occupational Health, Institute of Risk Analysis and Risk Communication, University of Washington, 4225 Roosevelt Way NE, Seattle, WA, United States. Electronic address: faustman@u.washington.edu.
authors: Elaine M
authors: EM
authors: Faustman
mesh_terms: D000107:Acetylation / Q000187:drug effects; D001151:Arsenic / Q000633:toxicity; D018053:Arsenites / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D004390:Chlorpyrifos / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D044127:Epigenesis, Genetic; D006657:Histones / Q000378:metabolism; D006801:Humans; D007306:Insecticides / Q000633:toxicity; D008745:Methylation / Q000187:drug effects; D058953:Neural Stem Cells / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017670:Sodium Compounds / Q000633:toxicity*
chemical_list: D018053:Arsenites; D002800:Cholinesterase Inhibitors; D006657:Histones; D007306:Insecticides; D017670:Sodium Compounds; C017947:sodium arsenite; D004390:Chlorpyrifos; D001151:Arsenic
keywords: Acetylation; Arsenic; Chlorpyrifos; Differentiation; Epigenetic; Histone 3; Methylation; Neurotoxicity