X-ray-induced damage repair in exponentially growing and growth arrested confluent poly(adenosine diphosphate-ribose)...

We studied the role of PARP in X-ray-induced damage repair using V79 Chinese hamster cells and two derivative cell lines ADPRT54 and ADPRT351 deficient in poly(adenosine diphosphate-ribose) polymerase (PARP) activity. We previously demonstrated that these PARP-deficient cells had drastically reduced levels of p53. Further, these cells were also deficient in downstream endpoints of p53 signaling. In the present study we showed that exponentially growing ADPRT54 and ADPRT351 were hypersensitive to X-radiation compared to the parental V79 cells. Under this condition of growth, although the parental V79 cells exhibit G1 arrest in response to X-irradiation, the PARP-deficient cells do not undergo this specific p53-dependent cell cycle arrest. In contrast, all the cell lines showed similar sensitivity to X-radiation under growth arrested conditions. Further, all the cell lines were equally proficient in performing potentially lethal damage repair (PLDR). Our findings suggest that: i) PARP is involved in X-ray-induced damage repair in replicating cells; ii) PARP is not required for X-ray-induced damage repair in quiescent cells; iii) PARP does not participate in PLDR; iv) deficiency of PARP may potentiate the cytotoxicity of X-irradiation by interfering with the p53-dependent G1 block that occurs after X-irradiation. These results suggest the intriguing possibility that the approach of inhibition of PARP combined with X-radiation may have therapeutic potential for the treatment of fast growing tumors. However, this approach may not be beneficial for slow growing/quiescent tumors.