Proximal tubular region-specific toxicity of cisplatin and investigation of its mechanism

Abstract

Cisplatin (CDDP) is an anticancer drug that causes severe kidney damage, especially in the S3 region of the proximal tubule. We showed that cytotoxicity to CDDP is the highest in the S3-derived cells. The S3-specific toxicity could not be explained by accumulation of Pt. Since the highest amount of Pt uptake was found 15 minutes after the exposure, the cytotoxicity by 15 min-exposure to CDDP was examined. The result showed that even the 15-min exposure to CDDP caused the highest cytotoxicity in S3 cells, suggesting the importance of shout-term cellular responses. We are attempting to establish the detection system of of CDDP – glutathione conjugates and investigate their dynamics.