{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T15:14:21Z","timestamp":1764688461401},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2004,2,19]],"date-time":"2004-02-19T00:00:00Z","timestamp":1077148800000},"content-version":"vor","delay-in-days":3701,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[1994,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Current evidence suggest an important role for increased repair of drug\u2010induced DNA damage as one of the major mechanisms involved in tumor cell resistance to cis\u2010DDP. In this study, we examined the DNA repair capacity and the activities of three DNA repair related proteins, namely, DNA polymerases \u03b1 and \u03b2, and total DNA ligase in cells of a malignant oligodendroglioma obtained from a patient before therapy and compared it with those of a specimen of the tumor acquired after the patient had failed cis\u2010DDP therapy. DNA repair capacity was quantitated as the extent of reactivation of the chloramphenicol\u2010O\u2010acetyltransferase (CAT) gene in a eukaryotic expression vector that has been damaged and inactivated by prior treatment with cis\u2010DDP and then transfected into the tumor cells. The extent of DNA\u2010platinum adduct formation in the expression vector was determined by flameless atomic absorption spectrometry. The level of cis\u2010DDP resistance of cells of the two tumors was determined with the capillary tumor stem cell assay. We observed a 2.8\u2010fold increased capacity to repair Pt\u2010DNA adducts and reactivate the CAT gene in cells of the tumor obtained after cis\u2010DDP therapy, compared to cells of the untreated tumor. This was associated with increases of 9.4\u2010fold and a 2.3\u2010fold, respectively, in DNA polymerase \u03b2 and total DNA ligase activities in cells of the treated tumor. At 5 \u03bcM cis\u2010DDP, there was a 5.9\u2010fold increase in the in vitro cis\u2010DDP resistance of post\u2010therapy tumor cells relative to cells of the untreated tumor. No significant difference in DNA polymerase \u03b1 activity was observed between the two tumors. These data suggest that the enhanced ability to repair cis\u2010DDP induced DNA damage, mediated, in part, by increased tumor DNA polymerase \u03b2 and DNA ligase activities, plays an important role in the in vivo acquisition of cis\u2010DDP resistance in human malignant gliomas, and that these proteins and\/or their encoding genes may represent critical targets for strategies to overcome such resistance clinically.<\/jats:p>","DOI":"10.1002\/jcb.240540103","type":"journal-article","created":{"date-parts":[[2005,5,28]],"date-time":"2005-05-28T21:23:33Z","timestamp":1117315413000},"page":"11-19","source":"Crossref","is-referenced-by-count":47,"title":["Enhanced repair of a cisplatin\u2010damaged reporter chloramphenicol\u2010O\u2010acetyltransferase gene and altered activities of DNA polymerases \u03b1 and \u03b2, and DNA ligase in cells of a human malignant glioma following in vivo cisplatin 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