Department of Environmental & Radiological Health Sciences, Colorado State University, USA.
Research and Development Center, Carlit Holdings Co. Ltd, Japan.
Biochem Biophys Res Commun. 2024 Jan 29;694:149386. doi: 10.1016/j.bbrc.2023.149386. Epub 2023 Dec 16.
Radiation exposure poses a significant threat to cellular integrity by inducing DNA damage through the generation of free radicals and reactive oxygen species. Ascorbic acid, particularly its derivative Palmitoyl Ascorbic Acid 2-Glucoside (PA2G), has demonstrated remarkable radioprotective properties. While previous research focused on its pre-irradiation application, this study explores the post-irradiation radiomitigation potential of PA2G. Our findings reveal that post-irradiation treatment with PA2G enhances cell survival and accelerates DNA repair processes, particularly the non-homologous end-joining (NHEJ) repair pathway. Notably, PA2G treatment reduces the frequency of lethal chromosomal aberrations and micronuclei formation, indicating its ability to enhance the repair of complex DNA lesions. Furthermore, PA2G is shown to play a role in potentially lethal damage repair (PLDR). These radioprotective effects are specific to NHEJ and ATM pathways, as cells deficient in these mechanisms do not benefit from PA2G treatment. This study highlights PA2G as a versatile radioprotector, both pre- and post-irradiation, with significant potential for applications in radiation therapy and protection, offering new insights into its mechanism of action. Further research is required to elucidate the precise molecular mechanisms underlying PA2G's radiomitigation effects and its potential clinical applications.
辐射暴露通过自由基和活性氧的产生诱导 DNA 损伤,对细胞完整性构成重大威胁。抗坏血酸,特别是其衍生物棕榈酰抗坏血酸 2-葡萄糖苷(PA2G),具有显著的放射防护特性。虽然以前的研究集中在其辐射前的应用,但本研究探讨了 PA2G 的辐射后辐射缓解潜力。我们的研究结果表明,PA2G 的辐射后处理可提高细胞存活率并加速 DNA 修复过程,特别是非同源末端连接(NHEJ)修复途径。值得注意的是,PA2G 处理可降低致死性染色体畸变和微核形成的频率,表明其增强复杂 DNA 损伤修复的能力。此外,PA2G 被证明在潜在致死性损伤修复(PLDR)中发挥作用。这些放射防护作用是 NHEJ 和 ATM 途径特异性的,因为缺乏这些机制的细胞不能从 PA2G 治疗中受益。这项研究强调了 PA2G 作为一种多功能的放射保护剂,无论是在辐射前还是辐射后,都具有在放射治疗和防护中的重要应用潜力,为其作用机制提供了新的见解。需要进一步研究阐明 PA2G 的辐射缓解作用的精确分子机制及其潜在的临床应用。