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Purpose: To determine the biological effectiveness of single,fractioned and continuous low dose rate irradiation on the human colorectal cancer cell line CL187 in vitro and explore the relevant molecular mechanisms.Materials and Methods: The CL187 cells were exposed to radiation of 6 MV X-ray at a high dose rate of 4Gy/min and 125I seed at a low dose rate of 2.77 cGy/h.Three groups were employed: single dose radiation group (SDR),fractioned dose radiation group (FDR) by 2Gy/f and continuous low dose rate radiation group (CLDR).The radiation doses were 0,2,4,6 and 8Gy,respectively.The responses of CL187 cells to distinct modes of radiation were evaluated by colony-forming assay,cell cycle progression as well as apoptosis analysis.Accordingly,we detected the expression patterns of DNA-PKcs,Ku70 and Ku80 by Western blotting.Results: The relative biological effect for 125I seeds compared with 6 MV X-ray was 1.42.48hrs after 4Gy irradiation,the difference between proportions of cells at G2/M phase of SDR and CLDR groups were statistically significant (p=0.026),so as the FDR and CLDR groups (p=0.005).48hrs after 4Gy irradiation,the early apoptosis rate of CLDR group was significantly higher than SDR and FDR groups (CLDR vs.SDR,p=0.001; CLDR vs.FDR,p=0.02).48hrs after 4Gy irradiation,the late apoptosis rate of CLDR group increased significantly compared with SDR and FDR group (CLDR vs.SDR,p=0.004; CLDR vs.FDR,p=0.007).DNA-PKcs and Ku70 expression levels in CLDR-treated cells decreased compared with SDR and FDR groups.Conclusions: Compared with the X-ray high dose rate irradiation,125I seeds CLDR showed more effective inhibition on CL187 cells,which was attributed mainly to induction of cell apoptosis and G2/M cell cycle arrest.Furthermore,125I seeds CLDR could impair the DNA repair capability by down-regulating DNA-PKcs and Ku70 expression.