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
✍ Scribed by Philip Bedford; Sharon A. Shellard; M. Claire Walker; Richard D. H. Whelan; John R. W. Masters; Bridget T. Hill
- Publisher
- John Wiley and Sons
- Year
- 1987
- Tongue
- French
- Weight
- 632 KB
- Volume
- 40
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Two sublines were derived from a human bladder carcinoma continuous cell line (RTI 12-P), one by exposure to fractionated X-irradiation (RTI IZ-DXRa) and the other by continuous exposure to cisplatin (RT 112-CP). RTI I2-DXR8 cells were I .6to 2-fold more sensitive to cisplatin and 2 analogues, carboplatin and iproplatin, compared with the parental line, whereas RTI 12-CP cells were 1.6-to 2.8-fold more resistant to these agents. Uptake of '95mcisplatin was elevated I .4-f0ld in RTI 12-DXR8 cells compared with RTI 12-P cells whereas uptake into RTII2-CP cells was similar to that of the parental line. Binding of '95mcisplatin to DNA was similar in all 3 lines. Levels of reduced glutathione were significantly elevated in RTI 12-CP cells and significantly reduced in R T I I2-DXR8 cells compared with the parental cells. In addition, activities of glutathione reductase and glutathione peroxidase were higher in RTI 12-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 crosslinks occurred in RTI12-DXR8 cells compared with the parental line, whereas crosslinking in RTI 12-CP cells, whilst initially similar to that seen in RTI 12-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.