Differential inhibitory effect of DNA-PK inhibitor (Ok-1035) on DNA repairin L5178Y mouse lymphoma cell lines

DNA damage repair was evaluated in two mouse lymphoma L5178Y (LY) cell line s differing in sensitivity to ionizing radiation. The cells were treated wi th OK-1035, a potent DNA-dependent protein kinase (DNA-PK) inhibitor, and i rradiated (8 Gy). The level of initial damage was similar in both LY cell l ines. In L5178Y cells the repair of 8 Gy-induced DNA damage proceeded ident ically in the inhibitor treated and untreated cells. In contrast, the level of residual damage in OK-1035 treated LY-R cells was considerably higher t han in untreated cells. The inhibitor affected LY-R cells preferentially in G1 and S phases, in agreement with cell-cycle specificity of DNA-PK. The r esults may indicate that DSB repair defect previously identified in LY-S ce lls is due to a lack of function of DNA-PK.