Institute of Astronautical Research, Japan Aerospace Exploration Agency, 3-1-1 Yoshinodai, Chuo-ku, Kanagawa 252-0022, Japan; Center for Sustainable Resource Science, The Institute of Physical and Chemical Research, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Institute of Astronautical Research, Japan Aerospace Exploration Agency, 3-1-1 Yoshinodai, Chuo-ku, Kanagawa 252-0022, Japan; Division of Genetics and Mutagenesis, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa 210-9501, Japan.
Life Sci Space Res (Amst). 2019 Feb;20:113-123. doi: 10.1016/j.lssr.2018.10.004. Epub 2018 Nov 1.
In the mid-1980s, space experiments began to examine if microgravity could alter the biological effects of space radiation. In the late 1990s, repair of DNA strand breaks was reported to not be influenced by microgravity using the pre-irradiated cells, because the exposure doses of space radiation were few due to the short spaceflight. There were, however, conflicting reports depending on the biological endpoints used in various systems. While almost no attempts were made to assess the possibility that the microgravity effects could be altered by space radiation. This was probably due to the general understanding that microgravity plays a major role in space and works independently from space radiation. Recent ground-based simulation studies focusing on DNA oxidative damage and signal transduction suggested that combined effects of microgravity and space radiation might exist. These studies also implicated the importance of research focusing not only on chromosomal DNA but also on cytoplasm, especially mitochondria. Therefore, we propose a new model which accounts for the combined-effects through the window of cellular responses. In this model, the interactions between microgravity and space radiation might occur during the following cellular-responses; (A) damaging and signaling by ROS, (B) damage responses on DNA (repair, replication, transcription, etc.), and (C) expression of gene and protein (regulation by chromatin, epigenetic control, etc.).
在 20 世纪 80 年代中期,太空实验开始研究微重力是否会改变空间辐射的生物学效应。在 20 世纪 90 年代末,据报道,使用预先辐照的细胞,由于空间飞行时间短,空间辐射的暴露剂量很少,DNA 链断裂的修复不受微重力影响。然而,由于在不同系统中使用的生物学终点不同,出现了相互矛盾的报告。虽然几乎没有尝试评估微重力效应是否可能因空间辐射而改变。这可能是因为普遍认为微重力在空间中起主要作用,并且与空间辐射独立作用。最近的基于地面的模拟研究集中在 DNA 氧化损伤和信号转导上,表明微重力和空间辐射的联合效应可能存在。这些研究还暗示了不仅关注染色体 DNA 而且关注细胞质(特别是线粒体)的研究的重要性。因此,我们提出了一个新的模型,通过细胞反应的窗口来解释联合效应。在这个模型中,微重力和空间辐射之间的相互作用可能发生在以下细胞反应过程中:(A)ROS 的损伤和信号传递,(B)DNA 的损伤反应(修复、复制、转录等),以及(C)基因和蛋白质的表达(染色质调控、表观遗传控制等)。