Enhancement of excision repair of cisplatin-DNA adducts by cell-free extract from a cisplatin-resistant rat cell line

To characterize the enhanced repair synthesis of defined DNA lesions, oligo deoxyribonucleotides a ere synthesized and inserted into plasmid DNA The in serted plasmid DNA was treated with cis-diamminedichloroplatinum(II) (cispl atin) and subjected to in vitro DNA repair assay with soluble extract from the rat liver cell line Ac2F. All cisplatin adducts tested stimulated DNA r epair synthesis. Moreover, two cisplatin-resistant cell lines, Ac2F-CR4 and Ac2F-CR10, were established by stepwise exposure of Ac2F cells to this dru g. Tnt DNA repair synthesis was enhanced 3- to 4-fold in the extract from c isplatin-resistant Ac2F cells relative to that from Ac2F cells. Such repair synthesis was suppressed by the specific DNA polymerase inhibitor aphidico lin. The results of dir present study suggested that the enhanced repair ac tivity induced by a cisplatin adduct can be detected by in vitro DNA repair assay with soluble cell extract. (C) 1999 Elsevier Science Inc.