Mismatch repair of cis-diamminedichloroplatinum(II)-induced DNA damage.
Because cytotoxicity by an alkylating agent such as N-methyl-N'-nitrosoguanidine is markedly increased in adenine methylase-deficient dam-3 Escherichia coli, it was of interest to assess whether mismatch repair was similarly important in the repair of DNA damage induced by cis-diamminedichloroplatinum(II) (CDDP). The results demonstrate that after exposure to 5-40 microM CDDP, dam-3 E. coli are 2-15-fold more sensitive to the cytotoxic effects of this agent. Further, dam-3 mutL451 E. coli deficient in mismatch repair was as resistant as wild type. trans-Diamminedichloroplatinum(II) treatment did not cause marked increments in cytotoxicity in dam-3 E. coli compared to wild type. The rate of excision of platinum was significantly reduced in dam-3 E. coli compared to wild type, demonstrating that differences in the repair of CDDP-induced DNA damage underlie enhanced cytotoxicity by this agent. Lastly, mutagenesis by CDDP was abrogated in umuDC- E. coli, showing that this gene product mediates mutagenesis by this agent.
D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D004260:DNA Repair; D004269:DNA, Bacterial / Q000235:genetics; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000187:drug effects; D010984:Platinum / Q000378:metabolism; D012293:Rifampin / Q000494:pharmacology
D004269:DNA, Bacterial; D010984:Platinum; D002945:Cisplatin; D012293:Rifampin