Transient cisplatin-resistant murine fibrosarcoma cell characterized by increased metallothionein content.
Cisplatin-resistant mouse fibrosarcoma cells, SSK-R, were isolated after short and low-dose drug treatment of the sensitive SSK cells in vitro. These SSK-R sublines exhibit up to sevenfold cisplatin resistance and are characterized mainly by an increased metallothionein content. Loss of drug resistance after about 140-180 cell divisions in drug-free medium coincides with loss of metallothionein content. The glutathione level is the same in the sensitive and resistant sublines; inhibition of glutathione synthesis by buthionine sulphoximine enhances the sensitivity in both cells lines by a factor of 2.7. The resistant sublines are not cross-resistant to radiation; a radiation exposure followed immediately by cisplatin treatment results in an additive effect. The cellular cisplatin content is slightly reduced in SSK-R2 cells and it remains at this level also upon loss of drug sensitivity.
Eichholtz-Wirth
H
H
GSF, Institut für Strahlenbiologie, Neuherberg, Federal Republic of Germany.
Born
R
R
Reidel
G
G
Hietel
B
B
D000818:Animals; D002106:Cadmium Radioisotopes; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004351:Drug Resistance; D005354:Fibrosarcoma / Q000737:chemistry*; D005978:Glutathione / Q000032:analysis; D008668:Metallothionein / Q000032:analysis*; D051379:Mice; D010984:Platinum / Q000032:analysis; D013052:Spectrometry, X-Ray Emission; D014407:Tumor Cells, Cultured
D002106:Cadmium Radioisotopes; D010984:Platinum; D008668:Metallothionein; D005978:Glutathione; D002945:Cisplatin