Biological Monitoring of Exposure to Cisplatin in Rats Using SOS Chromotest

Abstract

Cisplatin (CDDP) is a potent antitumor drug used in the treatment of a variety of solid tumors. The purpose of the present study was to establish screening biomarker of exposure to CDDP using SOS chromotest. The ultimate goal of this screen is to facilitate the choice of an effective drug and the prognosis of the therapy. In the current screening protocol, the SOS chromotests were performed on the urine of Sprague-Dawley rats administered intravenously with CDDP. Urine samples were collected individually in the metabolic cage at 6 (U0–6) and 12 hours (U6–12) after treatment and were tested their DNA damaging effects. The urine samples obtained from the rats administered with 1 mg/kg CDDP did not induce SOS response in our experimental conditions. At a dose of 5 mg/kg, two out of five rat showed more than 50% increase in the DNA damaging effect compared to that of the control. The genotoxic effect was observed only in the U0–6, whereas the U6–12 were not genotoxic but cytotoxic to the test strain. Similar results were obtained at a dose of 10 mg/kg: 5 out of 10 rats showed SOS response and the U6–12 were also proven to be cytotoxic. These results suggest that the method presented in this study could be used as a biomarker of exposure to CDDP.