Abstract
Molecular and cellular responses to protracted ionizing radiation exposures are poorly understood. Using immunofluorescence microscopy, we studied the kinetics of DNA repair foci formation in normal human fibroblasts exposed to X-rays at a dose rate of 4.5 mGy/min for up to 6 h. We showed that both the number of γH2AX foci and their integral fluorescence intensity grew linearly with time of irradiation up to 2 h. A plateau was observed between 2 and 6 h of exposure, indicating a state of balance between formation and repair of DNA double-strand breaks. In contrast, the number and intensity of foci formed by homologous recombination protein RAD51 demonstrated a continuous increase during 6 h of irradiation. We further showed that the enhancement of the homologous recombination repair was not due to redistribution of cell cycle phases. Our results indicate that continuous irradiation of normal human cells triggers DNA repair responses that are different from those elicited after acute irradiation. The observed activation of the error-free homologous recombination DNA double-strand break repair pathway suggests compensatory adaptive mechanisms that may help alleviate long-term biological consequences and could potentially be utilized both in radiation protection and medical practices.
Highlights
Ionizing radiation exposure leads to a variety of DNA lesions, but the fate of the cell is largely determined by DNA double-strand breaks
Primary cultures of diploid human fibroblasts were exposed to continuous X-ray radiation at a dose-rate of 4.5 mGy/min under normal growth conditions for up to 6 h
Using normal human skin fibroblasts, we measured the effects of a continuous 6-h exposure using X-ray radiation at a dose rate of 4.5 mGy/min on DNA double-strand breaks
Summary
Ionizing radiation exposure leads to a variety of DNA lesions, but the fate of the cell is largely determined by DNA double-strand breaks. HR repair is errorfree and slow (> 7 h [10]) and requires a sister chromatid as a template for DNA synthesis in the vicinity of a break on the damaged chromatid This pathway is active mainly in cells in S and G2 cell cycle phases [12]. HR is involved in the repair of collapsed replication forks [13] It is, important to know relative contributions of the two DNA double-strand break repair pathways in order to better predict or understand delayed consequences of exposure to radiation
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