Differential properties of cisplatin and tetraplatin with respect to cytotoxicity and perturbation of cellular glutathione levels.
We compared the cytotoxicity and the effects on the levels of cellular glutathione (GSH) of cisplatin and tetraplatin in the mouse mammary tumour cell line EMT6/P and a cisplatin-resistant variant. EMT6/CPR. EMT6/CPR showed a 2.5-fold resistance to cisplatin but no cross-resistance to tetraplatin. Basal cellular GSH levels in the resistant line were 1.7-fold those in the parent cell line. On exposure of cells to cisplatin, cellular GSH levels initially dropped in both cell lines but subsequently rose. At between 1 and 4 h after the onset of drug exposure, GSH levels were up to 2-fold the baseline levels. The cisplatin-resistant subline displayed higher GSH levels than the parent cell line at all time points. Tetraplatin failed to influence cellular GSH levels in either of the cell lines.
Müller
M R
MR
MRC Clinical Oncology and Radiotherapeutics Unit, Cambridge, UK.
Wright
K A
KA
Twentyman
P R
PR
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity*; D002460:Cell Line; D002945:Cisplatin / Q000627:therapeutic use / Q000633:toxicity*; D004396:Coloring Agents; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D005978:Glutathione / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000737:chemistry / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D009944:Organoplatinum Compounds / Q000627:therapeutic use / Q000633:toxicity*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D004396:Coloring Agents; D009944:Organoplatinum Compounds; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D005978:Glutathione; D002945:Cisplatin; C049777:ormaplatin