Abstract
Accumulating evidence indicates that the biological effects of low dose and low dose-rate radiation are different from those of high dose and high dose-rate radiation. To elucidate the molecular mechanisms involved in cellular responses to low dose and 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).
Here we show that in chicken DT40 cells irradiated with γ-rays at a low dose-rate (1 mGy/h), the growth delay in NHEJ-related KU70- and PRKDC-defective cells were remarkably higher than in cells defective for the HR-related RAD51B and RAD54 genes. One possibility is 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. The other factor to consider is the difference in the efficiency of NHEJ versus HR. On other word, NHEJ may be more efficient than HR for the repair of low numbers of DSBs.
RAD54-/-KU70-/- cells demonstrated their highest degree of growth delay after an X-irradiation with a high dose-rate of 0.9 Gy/min. However they showed a lower degree of growth delay than that seen in KU70-/- and PRKDC-/-/- cells exposed to low dose-rate irradiation. A backup DSB repair pathway may be activated in RAD54-/-KU70-/- cells irradiated with chronic low dose-rate radiation.
