The response of human breast tumour cell lines with altered polymerase beta levels to cisplatin and radiation.
MCF 7 (human breast carcinoma cells) and mutants transfected with the DNA polymerase beta gene were tested for response to cisplatin, radiation and combined treatments. The transfected cells showed a higher level of polymerase beta activity and were more resistant to radiation and cisplatin compared to the parental cell line. Further studies showed that for isosurvival treatments the mutant cells were more effective in sublethal radiation damage repair compared to the parental line. The combination of cisplatin with radiation showed effective radiosensitization which was less in the mutants compared to the parental line. In addition, the sequence of cisplatin before irradiation was more effective then cisplabn after irradiation. Pre-exposure to low levels of cisplatin for up to 24 h before irradiation showed a small significant adaptive response in one mutant line at 8 h and while similar trends were observed in the parental lines at earlier times they were not significant. In summary our data show that polymerase beta and thus base excision repair may play a role in cellular responses to cisplatin and radiation.
Raaphorst
G P
GP
ORCC, Ottawa, Ontario, Canada.
Cybulski
S E
SE
Sobol
R
R
Ng
C E
CE
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000532:radiotherapy*; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology*; D003131:Combined Modality Therapy; D019951:DNA Polymerase beta / Q000096:biosynthesis* / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D009154:Mutation; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D019951:DNA Polymerase beta; D002945:Cisplatin