Kumar Kamendra, Fornace Albert J, Suman Shubhankar
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.
Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC 20057, USA.
DNA (Basel). 2024 Sep;4(3):221-238. doi: 10.3390/dna4030015. Epub 2024 Aug 1.
Oxidative stress-mediated biomolecular damage is a characteristic feature of ionizing radiation (IR) injury, leading to genomic instability and chronic health implications. Specifically, a dose- and linear energy transfer (LET)-dependent persistent increase in oxidative DNA damage has been reported in many tissues and biofluids months after IR exposure. Contrary to low-LET photon radiation, high-LET IR exposure is known to cause significantly higher accumulations of DNA damage, even at sublethal doses, compared to low-LET IR. High-LET IR is prevalent in the deep space environment (i.e., beyond Earth's magnetosphere), and its exposure could potentially impair astronauts' health. Therefore, the development of biomarkers to assess and monitor the levels of oxidative DNA damage can aid in the early detection of health risks and would also allow timely intervention. Among the recognized biomarkers of oxidative DNA damage, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OxodG) has emerged as a promising candidate, indicative of chronic oxidative stress. It has been reported to exhibit differing levels following equivalent doses of low- and high-LET IR. This review discusses 8-OxodG as a potential biomarker of high-LET radiation-induced chronic stress, with special emphasis on its potential sources, formation, repair mechanisms, and detection methods. Furthermore, this review addresses the pathobiological implications of high-LET IR exposure and its association with 8-OxodG. Understanding the association between high-LET IR exposure-induced chronic oxidative stress, systemic levels of 8-OxodG, and their potential health risks can provide a framework for developing a comprehensive health monitoring biomarker system to safeguard the well-being of astronauts during space missions and optimize long-term health outcomes.
氧化应激介导的生物分子损伤是电离辐射（IR）损伤的一个特征，会导致基因组不稳定和慢性健康问题。具体而言，在IR暴露数月后，许多组织和生物流体中都报告了氧化DNA损伤随剂量和线性能量转移（LET）的持续增加。与低LET光子辐射相反，已知高LET IR暴露会导致DNA损伤的积累显著更高，即使在亚致死剂量下，与低LET IR相比也是如此。高LET IR在深空环境（即地球磁层之外）中普遍存在，其暴露可能会损害宇航员的健康。因此，开发用于评估和监测氧化DNA损伤水平的生物标志物有助于早期发现健康风险，并能及时进行干预。在公认的氧化DNA损伤生物标志物中，8-氧代-7,8-二氢-2'-脱氧鸟苷（8-OxodG）已成为一个有前景的候选物，表明存在慢性氧化应激。据报道，在等效剂量的低LET和高LET IR后，它会呈现出不同的水平。本综述讨论了8-OxodG作为高LET辐射诱导的慢性应激的潜在生物标志物，特别强调了其潜在来源、形成、修复机制和检测方法。此外，本综述还探讨了高LET IR暴露的病理生物学影响及其与8-OxodG的关联。了解高LET IR暴露诱导的慢性氧化应激、8-OxodG的全身水平及其潜在健康风险之间的关联，可以为开发一个全面的健康监测生物标志物系统提供框架，以在太空任务期间保障宇航员的健康，并优化长期健康结果。
