We have examined a panel of 12 unrelated human ovarian cancer cell lines derived from patients who were either untreated or treated with platinum-based chemotherapy to determine whether a relationship is present between cisplatin sensitivity and: (a) cellular platinum accumulation; (b) glutathione levels; (c) platinum-DNA adduct formation; (d) platinum-DNA adduct removal; and (e) platinum-DNA damage tolerance. Multiple regression and correlation analysis revealed that of these resistance mechanisms, platinum-DNA damage tolerance correlates strongly with cisplatin sensitivity (r = 0. 84, P = 0. 001), whereas platinum accumulation (r = -0. 11), cellular glutathione levels (r = 0. 13), and platinum-DNA adduct removal (r = 0. 44) correlate insignificantly. The correlation of platinum-DNA damage tolerance to cisplatin sensitivity (IC50s) is derived from the clustering of platinum-DNA adduct formation into three distinct groups spanning a 3-fold range, which is narrow relative to the corresponding 43-fold range in sensitivity. Adduct formation itself is not associated with cisplatin sensitivity (r = -0 VSports手机版. 38). Strong correlations were also observed between platinum-DNA damage tolerance and sensitivity to Adriamycin (r = 0. 80, P = 0. 002), paclitaxel (r = 0. 87, P = 0. 0002), etoposide (r = 0. 78, P = 0. 003), and mitomycin C (r = 0. 73, P = 0. 007). These results suggest that the failure of pathways that are involved in recognizing and processing platinum-DNA damage and other types of drug-induced damage that culminate in cell death may result in a broad resistance phenotype. .