title: Dependence of the cytotoxicity of DNA-damaging agents on the mismatch repair status of human cells.
abstract: 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.
authors.affiliation: Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.
authors.forename: Efterpi
authors.initials: E
authors.lastname: Papouli
authors.forename: Petr
authors.initials: P
authors.lastname: Cejka
authors.forename: Josef
authors.initials: J
authors.lastname: Jiricny
mesh_terms: 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
chemical_list: 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