Repair of trans-Pt(II) diamminedichloride DNA-protein crosslinks in normal and excision-deficient human cells

In this investigation the persistence of DNA-protein crosslike (DPC) induced by trans-Pt was determined in normal and excision-deficient xeroderma pigmentosum (XP) group A fibroblasts. After exposure to 50 μM trans-Pt for 2 h, the level of DPC increased in both cell types for several hours but by 12 h it was significantly less in normal cells. By 18 h it was approximately half the maximal value in normal cells but had decreased little in XP cells. When cells were incubated with trans-Pt and polymerase inhibitor, DNA single-strand breaks accumulated in normal but to a much lower level in XP cells. These single-strand breaks were presumably produced during excision repair and were roughly comparable in frequency to the number of DPC removed in normal cells during the same interval. By colony survival, trans-Pt was more toxic to XP cells. These results indicate that DPC were recognized in normal cells and repaired by the excision repair pathway. (orig.)