Low, but Not High, Doses of Cisplatin Damage Cochlear Hair Cells in C57 Mouse Organotypic Cultures.

The purpose of this study was to investigate the characteristics of cisplatin-induced C57 mouse cochlear hair cell damage in vitro. Forty-seven cochleae harvested from 2- to 4-day-old C57 mice were used. Forty specimens were treated with different concentrations of cisplatin (10, 25, 50, 100, 400, and 1,000 μmol/l) for 48 h. The remaining seven specimens were used as a control group. The rate of hair cell loss increased from 14.5 to 78.4% over cisplatin concentrations of 10 to 100 μmol/l, whereas hair cell loss decreased to 48.8 and 8.77% at concentrations of 400 and 1,000 μmol/l, respectively. Apoptosis was detected by DAPI staining in the areas of hair cell damage. Hair cell loss rates differed significantly among the cisplatin-treated groups. Linear regression analysis of cisplatin dose versus hair cell number showed a significant negative correlation for cisplatin doses up to 100 μmol/l and a positive correlation with further increases up to 1,000 μmol/l. We conclude that cisplatin-induced hair cell damage was concentration dependent only up to a certain dose and that injury resistance may occur in cochlear cells treated with higher doses of cisplatin.