Advance Access publication June 6, 2008 Assessment of Chemical Effects on Neurite Outgrowth in PC12 cells Using High Content Screening

Identification of chemicals that pose a hazard to the developing nervous system is the first step in reducing human exposure and preventing health risks to infants and children. In response to the need for more efficient methods to identify potential developmen-tal neurotoxicants, the present study evaluated the utility of an automated high content screening system to detect chemical effects on neurite outgrowth in Neuroscreen-1 cells (NS-1), a subclone of PC12 cells. Plating 2000 NS-1 cells per well with 100 ng/ml nerve growth factor for 96 h produced optimal neurite growth in a 96-well format. Using this protocol, five chemicals that had been previously shown to inhibit neurite outgrowth in PC12 cells were examined. Inhibition of neurite outgrowth (assessed as total neurite length per cell) was observed for all five chemicals. For three of the chemicals, inhibition was associated with decreased cell viability. To demonstrate the utilit