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 p olymerise beta gene were tested for response to cisplatin, radiation and co mbined treatments. The transfected cells showed a higher level of polymeris e beta activity and were more resistant to radiation and cisplatin compared to the parental cell line. Further studies showed that for isosurvival tre atments the mutant cells were more effective in sublethal radiation damage repair compared to the parental line. The combination of cisplatin with rad iation showed effective radiosensitization which was less in the mutants co mpared to the parental line. In addition, the sequence of cisplatin before irradiation was more effective then cisplabn after irradiation. Pre-exposur e to low levels of cisplatin for up to 24 h before irradiation showed a sma ll significant adaptive response in one mutant line at 8 h and while simila r trends were observed in the parental lines at earlier times they were not significant. In summary our data show that polymerise beta and thus base e xcision repair may play a role in cellular responses to cisplatin and radia tion.