Role of DNA double-strand break repair genes in cell proliferation under low dose-rate irradiation conditions.
Radiation-induced DNA double-stand breaks (DSBs) lead to numerous biological effects. 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 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, it is shown that in chicken DT40 cells irradiated with gamma-rays at a low dose-rate (2.4 cGy/day), the growth delay in NHEJ-related KU70- and PRKDC (encoding DNA-PKcs)-defective cells were remarkably higher than in cells defective for the HR-related RAD51B and RAD54 genes. DNA-PKcs- defective human M059J cells also showed an obvious growth delay when compared to control M059K cells. 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. These findings indicate that cellular responses to low dose-rate radiation are remarkably different from those to high dose-rate radiation. The fact that both DT40 and mammalian NHEJ-defective cells were highly sensitive to low dose-rate radiation, provide a foundation for the concept that NHEJ-related factors may be useful as molecular markers to predict the sensitivity of humans to low dose-rate radiation.
Tomita
Masanori
M
Radiation Safety Research Center, Central Research Institute of Electric Power Industry, Tokyo, Japan. mstomita@criepi.denken.or.jp
Morohoshi
Fumiko
F
Matsumoto
Yoshihisa
Y
Otsuka
Kensuke
K
Sakai
Kazuo
K
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology* / Q000528:radiation effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000528:radiation effects*; D002645:Chickens; D004247:DNA / Q000235:genetics* / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology* / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D011829:Radiation Dosage
D004247:DNA