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Molecular Pharmacology

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Abstract

Isolation and characterization of a cisplatin-resistant strain of Schizosaccharomyces pombe.

P Perego, G Jimenez and S B Howell
Molecular Pharmacology November 1996, 50 (5) 1080-1086;
P Perego
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G Jimenez
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S B Howell
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Abstract

A cis-diamminedichloroplatinum [DDP (cisplatin)]-resistant population of Schizosaccharomyces pombe was developed through chronic exposure of the 972 h- strain to increasing concentrations of the drug. The resulting cells, designated wtr2, were 5.25-fold resistant to DDP, are resistance was retained by clone isolated from this population in the absence of drug for > or = 5 months. After backcrossing and isolation of a single clone, random spore analysis gave a segregation ratio close to 1:1 for DDP resistance and sensitivity. Tetrad analysis confirmed a mendelian 2:2 segregation, suggesting that a single nuclear gene was responsible for the DDP-resistant phenotype. Stable diploids obtained from the mating of a resistant spore carrying the ade6-216 marker with the mei2-102-ade6-210 meiosis-deficient mutant remained resistant, indicating that the resistant phenotype was expressed dominantly. There was no difference between the accumulation of the DDP analog [3H]dichloro(ethylenediamine)-platinum(II) into whole cells derived from the sensitive and the resistant spores obtained from the last backcross. The resistant clones from a single tetrad did not have an increased level of glutathione and were collaterally sensitive to cadmium and arsenite. We conclude that in S. pombe, a stable and dominant DDP-resistant phenotype can be mediated by a single allele, that the phenotype is not accompanied by cross-resistance to cadmium or arsenite, and that the mechanism is not associated with a significant alteration in glutathione level or DDP uptake.

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Molecular Pharmacology
Vol. 50, Issue 5
1 Nov 1996
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Abstract

Isolation and characterization of a cisplatin-resistant strain of Schizosaccharomyces pombe.

P Perego, G Jimenez and S B Howell
Molecular Pharmacology November 1, 1996, 50 (5) 1080-1086;

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Abstract

Isolation and characterization of a cisplatin-resistant strain of Schizosaccharomyces pombe.

P Perego, G Jimenez and S B Howell
Molecular Pharmacology November 1, 1996, 50 (5) 1080-1086;
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