关键词: 高通量, 发育神经毒性, PC12细胞, 神经突起

Abstract: OBJECTIVE: Assessment of developmental neurotoxicity plays an important role in the protection of a child's health. In response to the need for more efficient methods to identify chemicals that pose a hazard to the developing nervous system, the present study evaluated the utility of an automated high throughput screening system to detect chemical effects on neurite outgrowth in PC12 cells. METHODS: Plating 2500 cells per well with 250 ng/mL nerve growth factor for 96 h in a 96_well format to assess neurite outgrowth. RESULTS: The present study assessed 8 chemicals that had been previously shown to affect neurite outgrowth in PC12 cells. 2 chemicals (Benzopyrene, U0126) were found to inhibit neurite outgrowth with the concentration that could decrease cell viability. K252a and dexamethasone were found to inhibit neurite outgrowth without any effect on cell viability. Lead acetate and chlorpyrifos were found to increase neurite outgrowth in cytotoxic concentration and valproic acid increased neurite outgrowth in non_cytotoxic concentration. Phenytoin had no effect on neurite outgrowth. Developmental neurotoxicity of another 5 chemicals that have not been reported were also assessed with this system. Amoxicillin, paracetamol, sorbitol and saccharin sodium had no effect on neurite outgrowth but dimethyl phthalate could increase neurite outgrowth in cytotoxic concentration. CONCLUSION: These results demonstrated that a high thrughput screening system could rapidly monitor chemical effects on neurite outgrowth in vitro. Concentration_response data for both neurite outgrowth and cell viability allowed for determination of specificity of chemical effects on a neurodevelopmental endpoint.

Key words: high throughput screening, developmental neurotoxicity, neurite outgrowth