Differential cytotoxic effects of methylmercury and organotin compounds on mature and immature neuronal cells and non-neuronal cells in vitro

Abstract

The neurotoxicity of methylmercury and organotin compounds was evaluated in vitro on the basis of their differential cytotoxic effects on neuronal cells (rat phaeochromocytoma cell PC12h, human neuroblastoma cell NB-1 and primary cultures of rat cerebellar cells) and non-neuronal cells (normal rat kidney epithelial cell NRK-52E and primary cultures of rat hepatocyte). In this system, neuronal cells show consistently higher sensitivity to the toxicity of methylmercury, trimethyltin and triethyltin, which are known to be neurotoxic, than non-neuronal cells, as judged by the 50% lethal concentrations (LC 50) of these compounds after 48 hr treatment. Tributyltin and triphenyltin, which have not yet been confirmed to be neurotoxic, also show higher toxicity to neuronal cells; their LC 50 values for neuronal cells are generally lower than those for non-neuronal cells, suggesting that they could be neurotoxic. Differential cytotoxic effects of these compounds on mature and immature neuronal cells were also investigated using nerve growth factor (NGF)-treated PC12h and cerebellar cells precultured for 15 days in vitro as mature neuronal cells. With this system, cerebellar cells precultured for 1 day in vitro and NGF-untreated PC12h as immature neuronal cells were shown to be more sensitive to the toxicity of methylmercury than mature neuronal cells, which is consistent with the higher vulnerability of the developing neural system to the toxicity of methylmercury. This assessment system for neurotoxic compounds based on differential cytotoxicity to neuronal and non-neuronal cells may be useful as a primary screening system for the neurotoxicity of environmental contaminants.