Walker rat carcinoma cells are exceptionally sensitive to cis-diamminedichloroplatinum(II) (cisplatin) and other difunctional agents but not defective in the removal of platinum-DNA adducts.
Cisplatin binds to cellular macromolecules (DNA, RNA and protein) to the same extent in wild-type Walker rat carcinoma cells and a variant sub-line of these cells resistant to cisplatin and to other difunctional, but not monofunctional cytotoxic agents. Wild-type Walker cells exhibit a unique sensitivity to DNA-bound cisplatin, while the resistant cells have a sensitivity that approximates to that of many normal and other tumour cell lines. Total DNA-bound adducts were lost from both sensitive and resistant Walker cells at similar rates. Equal numbers of DNA interstrand crosslinks and DNA-protein crosslinks were formed in both cell lines, and the rate of loss of both types of crosslinks was similar in the two lines. Therefore the unusual sensitivity of Walker cells to cisplatin is not due to a defect in their ability to remove these platinum-DNA adducts.
D000818:Animals; D001692:Biological Transport; D002279:Carcinoma 256, Walker / Q000235:genetics*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000378:metabolism / Q000633:toxicity*; D003432:Cross-Linking Reagents; D004249:DNA Damage; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000378:metabolism; D004351:Drug Resistance; D007621:Karyotyping; D009363:Neoplasm Proteins / Q000378:metabolism; D011485:Protein Binding; D051381:Rats
D003432:Cross-Linking Reagents; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D002945:Cisplatin