MISMATCH REPAIR OF CIS-DIAMMINEDICHLOROPLATINUM(II)-INDUCED DNA DAMAGE

  • 1 January 1985
    • journal article
    • research article
    • Vol. 28  (1) , 51-55
Abstract
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 determined whether mismatch repair was similarly important in the repair of DNA damage induced by cis-diamminedichloroplatinum (II) (CDDP) [antineoplastic agent]. After exposure to 5-40 .mu.M CDDP, dam-3 E. coli are 2- to 15-fold more sensitive to the cytotoxic effects of this agent. 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 Pt 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. Mutagenesis by CDDP was abrogated in umuDC- E. coli, showing that this gene product mediates mutagenesis by this agent.

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