Dependence of the cytotoxicity of DNA-damaging agents on the mismatch repair status of human cells.
Mismatch repair (MMR) deficiency was reported to increase resistance of mammalian cells to killing by several genotoxic substances. However, although MMR-deficient cells are approximately 100-fold more resistant to killing by S(N)1 type methylating agents than MMR-proficient controls, the sensitivity differences reported for the other agents were typically <2-fold. To test whether these differences were linked to factors other than MMR status, we studied the cytotoxicities of mitomycin C, chloroethylcyclohexyl nitrosourea, melphalan, psoralen-UVA, etoposide, camptothecin, ionizing radiation, and cis-dichlorodiaminoplatinum (cisplatin) in a strictly isogenic system. We now report that MMR deficiency reproducibly desensitized cells solely to cisplatin.
Papouli
Efterpi
E
Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.
Cejka
Petr
P
Jiricny
Josef
J
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D020137:Base Pair Mismatch / Q000502:physiology*; D002166:Camptothecin / Q000494:pharmacology; D002352:Carrier Proteins; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology; D004260:DNA Repair / Q000502:physiology*; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000494:pharmacology; D011564:Furocoumarins / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008558:Melphalan / Q000494:pharmacology; D016685:Mitomycin / Q000494:pharmacology; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000172:deficiency; D009607:Nitrosourea Compounds / Q000494:pharmacology; D009687:Nuclear Proteins
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D002352:Carrier Proteins; D011564:Furocoumarins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009607:Nitrosourea Compounds; D009687:Nuclear Proteins; D016685:Mitomycin; D005047:Etoposide; D000070957:MutL Protein Homolog 1; D002945:Cisplatin; D008558:Melphalan; D002166:Camptothecin