Department of Biomolecular Engineering, University of California, Santa Cruz, CA 95064, USA.
Mol Cell Biochem. 2011 Mar;349(1-2):213-8. doi: 10.1007/s11010-010-0641-0. Epub 2010 Nov 16.
The space radiation environment consists of trapped particle radiation, solar particle radiation, and galactic cosmic radiation (GCR), in which protons are the most abundant particle type. During missions to the moon or to Mars, the constant exposure to GCR and occasional exposure to particles emitted from solar particle events (SPE) are major health concerns for astronauts. Therefore, in order to determine health risks during space missions, an understanding of cellular responses to proton exposure is of primary importance. The expression of DNA repair genes in response to ionizing radiation (X-rays and gamma rays) has been studied, but data on DNA repair in response to protons is lacking. Using qPCR analysis, we investigated changes in gene expression induced by positively charged particles (protons) in four categories (0, 0.1, 1.0, and 2.0 Gy) in nine different DNA repair genes isolated from the testes of irradiated mice. DNA repair genes were selected on the basis of their known functions. These genes include ERCC1 (5' incision subunit, DNA strand break repair), ERCC2/NER (opening DNA around the damage, Nucleotide Excision Repair), XRCC1 (5' incision subunit, DNA strand break repair), XRCC3 (DNA break and cross-link repair), XPA (binds damaged DNA in preincision complex), XPC (damage recognition), ATA or ATM (activates checkpoint signaling upon double strand breaks), MLH1 (post-replicative DNA mismatch repair), and PARP1 (base excision repair). Our results demonstrate that ERCC1, PARP1, and XPA genes showed no change at 0.1 Gy radiation, up-regulation at 1.0 Gy radiation (1.09 fold, 7.32 fold, 0.75 fold, respectively), and a remarkable increase in gene expression at 2.0 Gy radiation (4.83 fold, 57.58 fold and 87.58 fold, respectively). Expression of other genes, including ATM and XRCC3, was unchanged at 0.1 and 1.0 Gy radiation but showed up-regulation at 2.0 Gy radiation (2.64 fold and 2.86 fold, respectively). We were unable to detect gene expression for the remaining four genes (XPC, ERCC2, XRCC1, and MLH1) in either the experimental or control animals.
空间辐射环境由被俘粒子辐射、太阳粒子辐射和银河宇宙辐射（GCR）组成，其中质子是最丰富的粒子类型。在执行登月或火星任务时，宇航员会持续暴露于 GCR 中，并且偶尔会暴露于太阳粒子事件（SPE）产生的粒子中，这是主要的健康关注点。因此，为了确定太空任务期间的健康风险，了解质子暴露对细胞的反应至关重要。已经研究了 DNA 修复基因对电离辐射（X 射线和伽马射线）的表达，但缺乏关于质子对 DNA 修复的反应的数据。使用 qPCR 分析，我们研究了在 0、0.1、1.0 和 2.0 Gy 四种不同质子剂量下，从受照射小鼠睾丸中分离出的 9 种不同 DNA 修复基因的表达变化。选择这些 DNA 修复基因是基于它们已知的功能。这些基因包括 ERCC1（5' 切口亚基，DNA 链断裂修复）、ERCC2/NER（打开损伤周围的 DNA，核苷酸切除修复）、XRCC1（5' 切口亚基，DNA 链断裂修复）、XRCC3（DNA 断裂和交联修复）、XPA（结合预切口复合物中的受损 DNA）、XPC（损伤识别）、ATA 或 ATM（双链断裂时激活检查点信号）、MLH1（复制后 DNA 错配修复）和 PARP1（碱基切除修复）。我们的结果表明，在 0.1 Gy 辐射下，ERCC1、PARP1 和 XPA 基因没有变化，在 1.0 Gy 辐射下上调（分别为 1.09 倍、7.32 倍和 0.75 倍），在 2.0 Gy 辐射下显著增加（分别为 4.83 倍、57.58 倍和 87.58 倍）。其他基因，包括 ATM 和 XRCC3，在 0.1 和 1.0 Gy 辐射下没有变化，但在 2.0 Gy 辐射下上调（分别为 2.64 倍和 2.86 倍）。我们无法在实验组或对照组动物中检测到其余四个基因（XPC、ERCC2、XRCC1 和 MLH1）的基因表达。
