Interplay of space radiation and microgravity in DNA damage and DNA damage response

Abstract

In space, multiple unique environmental factors, particularly microgravity and space radiation, pose constant threat to the DNA integrity of living organisms. Specifically, space radiation can cause damage to DNA directly, through the interaction of charged particles with the DNA molecules themselves, or indirectly through the production of free radicals. Although organisms have evolved strategies on Earth to confront such damage, space environmental conditions, especially microgravity, can impact DNA repair resulting in accumulation of severe DNA lesions. Ultimately these lesions, namely double strand breaks, chromosome aberrations, micronucleus formation, or mutations, can increase the risk for adverse health effects, such as cancer. How spaceflight factors affect DNA damage and the DNA damage response has been investigated since the early days of the human space program. Over the years, these experiments have been conducted either in space or using ground-based analogs. This review summarizes the evidence for DNA damage induction by space radiation and/or microgravity as well as spaceflight-related impacts on the DNA damage response. The review also discusses the conflicting results from studies aimed at addressing the question of potential synergies between microgravity and radiation with regard to DNA damage and cellular repair processes. We conclude that further experiments need to be performed in the true space environment in order to address this critical question.

Role of High-Linear Energy Transfer Radiobiology in Space Radiation Exposure Risks

“…These results confirmed that space flight damaged nuclear DNA along tracks reflecting the tracks of space-radiation exposure [28]. Other recent studies have reported cH2AX signals in cells flown in space [29], as well as other forms of DNA damage, including chromosome aberrations in astronauts' lymphocytes [30]. High-LET radiation can thus induce permanent genetic changes in somatic and germ cells and is usually more effective per unit of absorbed dose than low-LET radiation.…”

“…Several factors contribute to the large uncertainties in risk projection and hinder evaluations of the effectiveness of possible countermeasures, including radiation-quality effects at a low dose rate (ie, the inverse dose-rate effect, adaptive response, bystander effect, and cell competition) and microgravity [64]. To allow the assessment and management of human health risks in space, it is necessary to obtain more basic data on the combined effects of radiation under microgravity [30,65]. To address these serious problems, we developed 3-dimensional clinostat-synchronized heavy-ion and x-ray irradiation systems [66,67], which are expected to provide significant contributions to space radiation research, as a valuable platform for studies on the relative biological effectiveness and the combined effects of radiation under microgravity.…”

NASA GeneLab Platform Utilized for Biological Response to Space Radiation in Animal Models

“…From these terms, we observed several key pathways, including mitotic and cell cycle pathways, cancer-related pathways, hypoxia-related pathways, interferon pathways, and pathways related to radiation impact on cells ( Figure 6A). Cell cycle pathways [57], hypoxia [58], interferon dysregulation [59], and cancer [60][61][62] have all been observed in previous research studies as dysregulated due to spaceflight.…”

Space Radiation Biology for “Living in Space”

“…However, synergistic effects between radiation and μG have been reported [172][173][174][175][176][177], and they can sup-press each other's effects [172,178]. There is the still no consensus on whether radiation and μG have combined effects [179,180]. JAXA developed not only the Cell Biology Equipment Facility (CBEF) [181] but also a mouse habitat unit cage (MHU) [182], which provides long-term artificial gravity for control experiments in space.…”