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Effect of lower chlorinated hydroxylated-polychlorobiphenyls on development of PC12 cells

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Hydroxylated polychlorobiphenyls (OH-PCBs) are major metabolites of PCBs that are widely distributed in the environment. While the effects of penta- to hepta-chlorinated OH-PCBs on neuronal differentiation have been widely reported, those of lower chlorinated OH-PCBs have not been extensively studied. To investigate the effects of lower chlorinated OH-PCBs on neuronal development, we studied the effects of mono- to hexa-chlorinated OH-PCBs on PC12 cells. Morphological changes were examined using an automatic system IN Cell Analyzer. Seventeen of the 20 OH-PCBs investigated promoted neuronal elongation in an OH-PCB concentration-dependent manner, while three OH-PCB congeners suppressed neuronal elongation based on Dunnett’s analysis. In particular, the top five OH-PCBs (4OH-PCB2, 4′OH-PCB3, 4′OH-PCB25, 4′OH-PCB68, and 4′OH-PCB159), which have hydroxyl groups at the para-position and chlorine substitutions at the 2, 4, or 3′ positions, significantly promoted neuronal elongation. Moreover, these neuronal elongations were suppressed by U0126, and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 was observed in PC12 cells treated with 4OH-PCB2, 4′OH-PCB25, and 4′OH-PCB159. Taken together, our results indicate that the effect of OH-PCB on neuronal development is not dependent on the number of chlorine groups but on the chemical structure, and the mitogen-activated kinase kinase (MEK)-ERK1/2 signaling pathway is involved in this process.

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This work was supported by a grant from the Research Fellow of Japan Society for the Promotion of Science (JSPS KAKENHI Grant Number 2640107). We thank Dr. Hiroko Kitamoto and Yuka Yoshinouchi for helpful comments.

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Correspondence to Satomi Mizukami-Murata.

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Responsible editor: Philippe Garrigues

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Mizukami-Murata, S., Fujita, K. & Nakano, T. Effect of lower chlorinated hydroxylated-polychlorobiphenyls on development of PC12 cells. Environ Sci Pollut Res 25, 16434–16445 (2018).

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  • Lower chlorinated OH-PCBs
  • PC12 cells
  • Neuronal development
  • MEK-ERK1/2 signaling pathway