Differential epigenetic effects of chlorpyrifos and arsenic in proliferating and differentiating human neural progenitor cells

- We evaluated histone modifications in hNPC exposed to chlorpyrifos or arsenic.
- Differentiation status influences histone modifications with chlorpyrifos exposure.
- Differentiation status influences histone modifications with arsenic exposure.
- Protein expression levels of differentiation markers influenced by arsenic.
- Protein expression levels of differentiation markers influenced by chlorpyrifos.

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.