Differential expression of collateral sensitivity or resistance to cisplatin in human bladder carcinoma cell lines pre‐exposed in vitro to either X‐irradiation or cisplatin

Two sublines were derived from a human bladder carcinoma continuous cell line (RTI12‐P), one by exposure to fractionated X‐irradiation (RTI12‐DXR8) and the other by continuous exposure to cisplatin (RTI12‐CP). RTI12‐DXR8 cells were 1.6‐ to 2‐fold more sensitive to cisplatin and 2 analogues, carboplatin and iproplatin, compared with the parental line, whereas RTI12‐CP cells were 1.6‐ to 2.8‐fold more resistant to these agents. Uptake of 195mcisplatin was elevated 1.4‐fold in RTI12‐DXR8 cells compared with RTI12‐P cells whereas uptake into RTI12‐CP cells was similar to that of the parental line. Binding of 195mcisplatin to DNA was similar in all 3 lines. Levels of reduced glutathione were significantly elevated in RTI 12‐CP cells and significantly reduced in RTI12‐DXR8 cells compared with the parental cells. In addition, activities of glutathione reductase and glutathione peroxidase were higher in RTI12‐CP cells than in the parental cells whereas the activity of glutathione‐S‐transferase was similar in all 3 cell lines. A 2.5‐fold greater induction of DNA‐DNA interstrand cross‐links occurred in RTI12‐DXR8 cells compared with the parental line, whereas crosslinking in RTI12‐CP cells, whilst initially similar to that seen in RTI12‐P cells, was significantly elevated at later times. These findings suggest that mechanisms associated with the expression of resistance and collateral sensitivity to cisplatin may differ.