Abstract
Manned space exploration was initiated in China in 1992, and substantial progress has been made. The next step is to build the Chinese Space Station (CSS), which is planned to be launched in 2020. The CSS will provide an on-orbit laboratory for experimental studies including space radiation research. The health risk of space radiation, especially carcinogenesis, is a major concern for long-term space exploration. Establishing a risk assessment system suitable for Chinese astronauts and developing effective countermeasures are major tasks for Chinese space radiobiologists. The Institute of Space Life Sciences, Soochow University has focused on these topics for years. We established cancer models with low-dose-rate exposure of alpha particles, and elucidated a microRNA-TGFβ network regulating bystander effects and a lncRNA-cytoskeleton network regulating genomic instability induced by ionising radiation. We also confirmed the radioresistance of quiescent cells, which inspires a potential strategy to improve individual radioresistance during long-term space travel. However, we believe that a multi-disciplinary strategy must be developed to protect astronauts from highly energised space radiation.
1. Recent progress on building the chinese space station
The Chinese Space Station (CSS) will be launched in 2020 and will serve as a research laboratory in outer space for at least one decade. There will be three experiment racks in the CSS available for radiobiological studies. The life ecological experiment rack is well equipped with a life support system and radiation monitoring system, and is suitable for studies with various experimental models. The biotechnology experiment rack is for tissue culture, protein crystallisation, biomechanical studies, etc. The third rack is for space radiation exposure outside the experimental modules. In addition, sample storage and observation stations will be included.
Two large-scale programmes with relevance to space radiobiological study will be funded and performed in China in the future. One is the construction of a manned moon base and the other is exploratory missions to Mars. As space radiation is one of the main threats to Chinese astronauts and her international partners in manned explorations to the moon and Mars, fundamental radiobiological studies to address these concerns have been initiated in China.
The CSS will not only provide platforms for Chinese scientists to perform experimental studies in outer space, but will also provide opportunities for open international co-operations. At the Global Space Exploration Conference (GLEX 2017), it was announced that the CSS will open to international collaboration. In 2018, the Chinese Space Agency officially announced 70 projects as the first series of scientific studies on the CSS; these were proposed by experts from more than 20 countries.
2. Recent Progress on Chinese space radiation research
2.1. Biological effects of low-dose radiation
To support the booming field of life sciences in space, several research centres that are dedicated to space radiobiological studies have been set up, including the Institute of Space Life Sciences, Soochow University in 2016. Multi-disciplinary studies have been performed, and some progress has been made at the institute, especially in radiation risk assessment and the development of countermeasures against space radiation.
Due to the low dose rate of space radiation, bystander effects, or abscopal effects in vivo, are dominant; these increase concerns about the health risk of space radiation to astronauts. Several signalling factors mediating bystander effects, including TGFβ, CPR-4, etc., have been identified. We elucidated a feedback loop of a miR-663-TGFβ network which suppresses out-of-field cells to secret bystander signals; this suggested that bystander effects mediated by TGFβ are not enhanced unlimitedly.
Risk of cancer is one of the major health issues faced by astronauts. However, the contribution of bystander effects to radiation-induced carcinogenesis remains vague. We exposed human lung epithelial cells to 20 mGy of alpha particles every 3 days to simulate space radiation, and found that long-term low-dose-rate exposure induced lung carcinoma in a dose-dependent manner, and the malignancy was higher than the same dose received as a single exposure. These results confirmed the high cancer risk of low-dose space radiation.
Detailed studies on the biological effects of space radiation are essential to provide considerable data to reduce the uncertainty of risk assessment of space radiation. The skin dose limits of Chinese astronauts for short-term low-earth-orbit missions are 0.15 Sv for 3 days, 0.20 Sv for 7 days, and 0.40 Sv for 30 days. In the coming CSS era, Chinese astronauts will spend much longer in space; dose limits for long-term space missions will be released shortly. A risk assessment model including recently published data, particularly data on Chinese cancer incidence and death rates, is still under development.
2.2. Mechanism underlying space radiobiological effects
The generally accepted dogma is that DNA is the target of ionising radiation. However, we believe that the cellular cytoskeleton is another of the major targets of ionising radiation because it is a ubiquitous subcellular organelle maintaining cell morphology, mediating material transportation, and sensing mechanical alterations inside a cell. We identified a radiation-inducible long non-coding RNA, namely LNC CRYBG3, that regulated cytokinesis, migration, and metabolism by interacting directly with the actin cytoskeleton. LNC CRYBG3 binds to the 14Ser of G-actin and inhibits the assembly of F-actin, which results in an incomplete cytoplastic division and consequent genomic instability. Obviously, the cytoskeleton-lncRNA network plays a very important role in regulating carcinogenesis associated with space radiation.
We further confirmed the functions of LNC CRYBG3 in regulating the carcinogenic effects of space radiation. LNC CRYBG3 was found to bind with LDHA to promote glucolysis, and LNC CRYBG3 was found to bind Bubs to interfere with the spindle assembly and separation of sister chromatids, resulting in aneuploidy and genomic instability. Therefore, a piece of radiation-induced long non-coding RNA leads to carcinogenesis by interacting with multiple targets.
2.3. Countermeasures against space radiation
Shielding cannot completely block highly energised space radiation. Anti-radiation medicine is not the first option, either. Novel strategies against space radiation have to be developed for long-term space exploration. Very possibly, a multi-disciplinary strategy will be taken in the future. It is generally believed that cells which are more proliferative are also more radiosensitive. Our previous work confirmed that quiescent cells are relatively resistant to ionising radiation, including high z and high-energy particles, due to the relatively low expression of RAC2, a main subunit of NADPH oxidase, and consequent low yields of intrinsic reactive oxygen species. These findings imply that risk assessment of space radiation based on results obtained with routine exponentially growing cells might be overestimated. These findings also highlight the potential application of cellular metabolism for modulating individual radiosensitivity.