Production of reactive oxygen species (ROS) by cisplatin and oxaliplatin, but not carboplatin is increased by reducing the expression of APE1 in sensory neuronal cultures.

<p>Neuronal cultures were exposed to siRNAs on days 3-5 in culture then exposed to various concentrations of platins for 24 hours starting on day 11 in culture. ROS generation was measured by Carboxy-H2DCFDA and FACS analysis. The left panels show representative FACS for cells treated with various concentrations of cisplatin (A), oxaliplatin (B) or carboplatin (C) and scramble siRNA (SCsiRNA) or APE1siRNA as indicated. The panels on the right show the quantification of data from 4-6 independent harvests. Each column represents the mean ± SEM of the percent of ROS positive cells from cultures treated with SCsiRNA (lightly shaded) or with APE1siRNA (heavy shaded) and treated with various concentrations of cisplatin (A); oxaliplatin (B) or carboplatin (C) as indicated. An asterisk indicates significant difference in the number of ROS positive cells in the absence or presence of drug treatment, whereas a cross indicates significant difference in cultures treated with SCsiRNA versus APE1siRNA using Student's <i>t</i>-test.