Abstract
The lack of information on how biological systems respond to low-dose and low dose-rate exposures makes it difficult to accurately assess the carcinogenic risks. This is of critical importance to space radiation, which remains a serious concern for long-term manned space exploration. In this study, the γ-H2AX foci assay was used to follow DNA double-strand break (DSB) induction and repair following exposure to neutron irradiation, which is produced as secondary radiation in the space environment. Human lymphocytes were exposed to high dose-rate (HDR: 0.400 Gy/min) and low dose-rate (LDR: 0.015 Gy/min) p(66)/Be(40) neutrons. DNA DSB induction was investigated 30 min post exposure to neutron doses ranging from 0.125 to 2 Gy. Repair kinetics was studied at different time points after a 1 Gy neutron dose. Our results indicated that γ-H2AX foci formation was 40% higher at HDR exposure compared to LDR exposure. The maximum γ-H2AX foci levels decreased gradually to 1.65 ± 0.64 foci/cell (LDR) and 1.29 ± 0.45 (HDR) at 24 h postirradiation, remaining significantly higher than background levels. This illustrates a significant effect of dose rate on neutron-induced DNA damage. While no significant difference was observed in residual DNA damage after 24 h, the DSB repair half-life of LDR exposure was slower than that of HDR exposure. The results give a first indication that the dose rate should be taken into account for cancer risk estimations related to neutrons.
Highlights
The integrity of an individual’s genome is continuously challenged by both endogenous and environmental mutagens
It was noted that the γ-H2AX foci formation after exposure to high dose-rate (HDR) was higher than that after low dose-rate (LDR), which appeared to be a statistically significant dose-rate effect (p < 0.05)
This was the result of simultaneous DNA double-strand break (DSB) induction and repair during LDR exposure, resulting in a lower number of γ-H2AX foci by the completion of exposure
Summary
The integrity of an individual’s genome is continuously challenged by both endogenous and environmental mutagens These damaging agents can induce a wide variety of lesions in the DNA, such as single-strand breaks (SSBs), double-strand breaks (DSBs), oxidative lesions and pyrimidine dimers [1]. Inaccurate repair or lack of repair of DSB can lead to cell death or mutations. The latter has been confirmed by experimental evidence on a causal link between the generation of DSBs and the induction of chromosomal translocations with tumourigenic potential [3]. To maintain the genomic integrity of DNA, cells have a complex set of signalling pathways to repair these DSBs, known as the DNA damage response pathway. Recent evidence shows that different particles with similar linear energy transfer (LET) values induce DSB damage of different complexities, pointing to a critical impact of the particle track core diameter on the type of DNA damage [7]
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