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Eichholtz-Wirth, H. ; Born, R. ; Reidel, G.* ; Hietel, B.

Transient cisplatin-resistant murine fibrosarcoma cell characterized by increased metallothionein content.

J. Cancer Res. Clin. Oncol. 119, 227-233 (1993)

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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.

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