Mismatch repair of cis-diamminedichloroplatinum(II)-induced DNA damage
Department of Biochemistry and Molecular Pharmacology
Medical Subject Headings
Cell Survival; Cisplatin; *DNA Repair; DNA, Bacterial; Drug Resistance, Microbial; Escherichia coli; Mutation; Platinum; Rifampin
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.
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Citation: Mol Pharmacol. 1985 Jul;28(1):51-5.
Fram, Robert J.; Cusick, Paul S.; Wilson, John M.; and Marinus, Martin G., "Mismatch repair of cis-diamminedichloroplatinum(II)-induced DNA damage" (1985). Biochemistry and Molecular Pharmacology Publications and Presentations. Paper 23.