Genotoxicity, and Oxidative Stress in Pc-12 Cells

Previous studies have indicated that heavy metal exposure can have an effect on the central nervous system. However, research has been inadequate to fully support this claim. The aim of this work was to determine the toxic effects of heavy metal ions including Fe, Fe, Hg, Mn, Cd, Mg, and Pb on nerve cells (e.g. PC12). PC12 cells were incubated with the metal ions at four concentrations, i.e. 12.5 M, 25.0 M, 250 M, and 625 M. The incubation periods initially tested were 2-hour, 4-hour, and 19-hour. The 4-hour incubation period was selected for further studies. Lactate dehydrogenase (LDH) assay was used to assess the cytotoxicity of selected metals. LDH is an enzyme present in most cells that is released into the cell culture medium upon damage of the cytoplasmic membrane. PC12 cells showed signs of cytotoxicity to all metal ions tested with the exception of Mn. Mn had little to no effect on PC12 cells. Fe and Mg showed the most toxicity to PC12 cells. Interestingly, Fe was found much less toxic to PC12 cells compared with Fe. The Comet assay showed an increase in DNA damage at both the 16.7 μM and 166.7 μM exposures. Our results indicate that exposure to Fe, Fe, Hg, Cd, Mg, and Pb at high and low concentrations induces cytotoxic and genotoxic effects in PC-12 cells, and its toxicity may be mediated through oxidative stress. Further studies are underway to investigate their mechanism of toxicity. Future studies will include oxidative status assessment and the profiling of monoamino neurotransmitters for PC12 cells after exposure to heavy metals.