Phenotypic reversion of cisplatin resistance in human cells accompanies reduced host cell reactivation of damaged plasmid.
Revertant cell lines were established from cisplatin (CP) resistant HeLa cells. Expression of CP damaged plasmid DNA carrying bacterial chloramphenicol acetyltransferase (CAT) gene after transfection into cells was measured. Revertant cells showed reduced host cell reactivation of damaged plasmid, as compared to resistant cells. Addition of aphidicolin, an inhibitor for DNA polymerase alpha, to resistant cells effectively blocked enhanced plasmid reactivation and acquired resistance. The results are consistent with the notion that cellular ability in repair CP-damaged DNA is a mechanism for CP resistance.
Chao
C C
CC
Department of Biochemistry, Chang Gung Medical College, Taoyuan, Taiwan.
Lee
Y L
YL
Lin-Chao
S
S
D016590:Aphidicolin; D002470:Cell Survival; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004260:DNA Repair; D004224:Diterpenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D006367:HeLa Cells; D006801:Humans; D010641:Phenotype; D010957:Plasmids / Q000187:drug effects
D004224:Diterpenes; D016590:Aphidicolin; D004247:DNA; D002945:Cisplatin