Repair Kinetics of DNA Double Strand Breaks Induced by Simulated Space Radiation.

Takashi Oizumi,Tomoo Funayama,Souichiro Yamabe,Asako J Nakamura,Rieko Ohno

doi:10.3390/life10120341

Abstract

Radiation is unavoidable in space. Energetic particles in space radiation are reported to induce cluster DNA damage that is difficult to repair. In this study, normal human fibroblasts were irradiated with components of space radiation such as proton, helium, or carbon ion beams. Immunostaining for γ-H2AX and 53BP1 was performed over time to evaluate the kinetics of DNA damage repair. Our data clearly show that the repair kinetics of DNA double strand breaks (DSBs) induced by carbon ion irradiation, which has a high linear energy transfer (LET), are significantly slower than those of proton and helium ion irradiation. Mixed irradiation with carbon ions, followed by helium ions, did not have an additive effect on the DSB repair kinetics. Interestingly, the mean γ-H2AX focus size was shown to increase with LET, suggesting that the delay in repair kinetics was due to damage that is more complex. Further, the 53BP1 focus size also increased in an LET-dependent manner. Repair of DSBs, characterized by large 53BP1 foci, was a slow process within the biphasic kinetics of DSB repair, suggesting non-homologous end joining with error-prone end resection. Our data suggest that the biological effects of space radiation may be significantly influenced by the dose as well as the type of radiation exposure.

Highlights

Exposure to ionizing radiation is one of the problems associated with human activities in space.The average annual dose of ionizing radiation on the ground is 2.4 mSv, whereas the average exposure on the International Space Station (ISS) is 0.5–1 mSv per day [1]
Using cocktail acceleration technology of Takasaki Ion Accelerators for Advanced Radiation Application (TIARA) cyclotron facility at Quantum and Radiological Science and Technology (QST)-Takasaki that can switch between low-linear energy transfer (LET) helium ions and high-LET carbon ions in a very short period of time, we report for the first time the effects of a mix of carbon and helium radiation on DNA damage repair
Heavy ions account for only 1% of space radiation, their biological effects are considered significant because heavy ions induce complex damage in DNA [5,6,7]

Summary

Introduction

Exposure to ionizing radiation is one of the problems associated with human activities in space. The average annual dose of ionizing radiation on the ground is 2.4 mSv, whereas the average exposure on the International Space Station (ISS) is 0.5–1 mSv per day [1]. Astronauts experience exposure of 1–2 mSv/day in deep space, and the cumulative effective radiation dose for a Mars mission is estimated to be as high as 1 Sv [2]. Space radiation comprises of galactic cosmic rays (GCRs) and solar particle events (SPEs), which contain approximately 85% protons, 14% helium ions, and 1% high-energy heavy ions (known as HZE particles) [3]. Heavy ion beams with high linear energy transfer (LET) in space radiation are known to cause cluster DNA damage in which multiple. Compared to X-rays or γ-rays, heavy ion beams cause more chromosomal aberrations such as dicentric chromosomes, translocations, and deletion mutations, resulting in significant biological effects [8,9,10,11,12,13,14,15]

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Conclusion