Abstract
“Dose-rate effect” has been well known as a result of sub-lethal damage repair during chronic irradiation. To elucidate the mechanisms involved in cellular responses to low dose-rate radiation, it is informative to clarify the roles of DNA double-stand break (DSB) repair related genes. In higher vertebrate cells, there are at least two major DSB repair pathways, namely non-homologous end-joining (NHEJ) and homologous recombination (HR). In chicken DT40 cells irradiated with γ-rays at a low dose-rate (1 mGy/hr), the growth delay in NHEJ-related KU70-defective cells was remarkably higher than in cells defective for the HR-related RAD54 genes. RAD54-/-KU70-/- cells demonstrated the highest degree of growth delay after high dose-rate (0.9 Gy/min) irradiation. However they showed a lower degree of growth delay than that seen in KU70-/- cells exposed to low dose-rate irradiation. Next, we evaluated the colony forming ability during low-dose rate irradiation. In this case, KU70-/- cells also showed the highest sensitivity.
These results are possibly explained by the fluctuation in activity of the two DSB repair pathways, NHEJ and HR, during cell cycle. NHEJ is a relatively stable DSB repair pathway during the cell cycle, but HR is efficient in the late S and G2 phases. Another possibility is the difference in the efficiency of NHEJ versus HR, i.e. NHEJ may be more efficient than HR for the repair of less frequent DSBs produced by low dose-rate irradiation. A backup DSB repair pathway may be activated in RAD54-/-KU70-/- cells irradiated with chronic low dose-rate radiation. Our obtained results suggest that the risk from low-dose rate radiation cannot be extrapolated from the results of high dose-rate radiation.
