RT Journal Article
SR Electronic
T1 Isolation and characterization of a cisplatin-resistant strain of Schizosaccharomyces pombe.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1080
OP 1086
VO 50
IS 5
A1 P Perego
A1 G Jimenez
A1 S B Howell
YR 1996
UL http://molpharm.aspetjournals.org/content/50/5/1080.abstract
AB 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.