The aim of this study was to assess niraparib (MK-4827), a novel 
poly(ADP-Ribose) polymerase (PARP) inhibitor, for its ability to radiosensitize 
human tumor cells. Human tumor cells derived from lung, breast and prostate 
cancers were tested for radiosensitization by niraparib using clonogenic 
survival assays. Both p53 wild-type and p53-defective lines were included. The 
ability of niraparib to alter the repair of radiation-induced DNA double strand 
breaks (DSBs) was determined using detection of γ-H2AX foci and RAD51 foci. 
Clonogenic survival analyses indicated that micromolar concentrations of 
niraparib radiosensitized tumor cell lines derived from lung, breast, and 
prostate cancers independently of their p53 status but not cell lines derived 
from normal tissues. Niraparib also sensitized tumor cells to H2O2 and converted 
H2O2-induced single strand breaks (SSBs) into DSBs during DNA replication. These 
results indicate that human tumor cells are significantly radiosensitized by the 
potent and selective PARP-1 inhibitor, niraparib, in the in vitro setting. The 
mechanism of this effect appears to involve a conversion of sublethal SSBs into 
lethal DSBs during DNA replication due to the inhibition of base excision repair 
by the drug. Taken together, our findings strongly support the clinical 
evaluation of niraparib in combination with radiation.