Formation and Repair of Cisplatin-induced Adducts to DNA in Cultured Normal and Repair-deficient Human Fibroblasts

摘要: The formation and repair of cisplatin [cis-PtCl2(NH3)2] adducts in the DNA cultured normal repair-deficient human fibroblasts are presented relation to cell survival after treatment. Directly treatment with cisplatin, (MB), Fanconi's anemia (FA), xeroderma pigmentosum (XP) four platinated products found. major adduct is bound two neighboring guanines, Pt-GG (62-75%). A less abundant product an AG sequence (Pt-AG). Binding guanines separated by one or more bases opposite strands (together measured as G-Pt-G) monofunctionally guanine (Pt-G) also found small amounts. distribution similar that previously, vitro systems well living cells. treatment, removal cisplatin-DNA fast FA fibroblasts, whereas XP proceeds slowly throughout period studied. Both extremely sensitive regard killing. For this sensitivity may be attributed fact these cells initially DNA-adducts formed than and/or their known deficiency interstrand cross-links. caused process, excision repair.