title: Differential properties of cisplatin and tetraplatin with respect to cytotoxicity and perturbation of cellular glutathione levels.
abstract: 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.
authors.affiliation: MRC Clinical Oncology and Radiotherapeutics Unit, Cambridge, UK.
authors.forename: M R
authors.initials: MR
authors.lastname: Müller
authors.forename: K A
authors.initials: KA
authors.lastname: Wright
authors.forename: P R
authors.initials: PR
authors.lastname: Twentyman
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D004396:Coloring Agents; D009944:Organoplatinum Compounds; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D005978:Glutathione; D002945:Cisplatin; C049777:ormaplatin