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METHYLMERCURY BUT NOT MERCURIC CHLORIDE INDUCES APOPTOTIC CELL DEATH IN PC12 CELLS.
Citation:
Parran, D., L. D. White, AND S Barone. METHYLMERCURY BUT NOT MERCURIC CHLORIDE INDUCES APOPTOTIC CELL DEATH IN PC12 CELLS. Presented at 18th Neurotoxicology Conference, Colorado Springs, CO, 9/23-26/2000.
Description:
Normal development of the nervous system requires the process of apoptosis, a form of programmed cell death, to remove superfluous neurons. Abnormal patterns of apoptosis may be a consequence of exposure to environmental neurotoxicants leading to a disruption in the tightly regulated process of neuronal development. Exposure to the developmental neurotoxicant methylmercury (CH3Hg) has been demonstrated to promote apoptosis during development in rodents, but little work have been done to elucidate the mechanism(s) of action. Using an in vitro model, rat pheochromocytoma (PC12) cells, we examined the effects CH3Hg and mercuric chloride (HgCl2) on cell death. PC12 cells were exposed to 0, 0.01, 0.03, 0.1, 0.3, 1, 3 or 10 mM of either CH3Hg or HgCl2 in the presence or absence of 50 ng/ml nerve growth factor (NGF) for 24 hours. Following exposure, oligonucleosomal fragmented DNA, an endpoint of apoptosis, was quantified by ELISA. Determinations of alterations in cell size and morphology were also made. In the absence of NGF, control levels of fragmented DNA were approximately 8-12 times higher than in the presence of NGF. In the presence of NGF, CH3Hg increased levels of fragmented DNA 10-40% at concentrations of 1, 3 and 10 mM, while HgCl2 had no significant effect on fragmented DNA at any of the tested concentrations. This trend of increased fragmented DNA following CH3Hg exposure was further characterized by TUNEL immunohistochemistry, but no increase TUNEL staining was evident following HgCl2 exposure. Decreases in cell size were also observed following exposure to CH3Hg. In the presence of NGF, a significant decrease in cell size was observed at 0.3-10 mM of CH3Hg, while no significant change in cell body size was seen following exposure to HgCl2. These data suggest that, in the presence of NGF, CH3Hg but not HgCl2, induces apoptotic cell death. (DKP was supported by NIEHS Training Grant T32ES07126). (This abstract does not necessarily reflect EPA policy)