Long-duration space missions outside low earth orbit will expose astronauts to a cumulative dose of high-energy particle radiation especially to highly damaging heavy ion radiation, which poses considerable risk to astronauts’ health. The purpose of the current study was to quantitatively identify oxidatively induced DNA base modifications and assess status of the repair pathways involved in removing the modified bases in mouse intestinal cells after exposure to γ-rays and iron radiation. Mice (C57BL/6J; 6 to 8 weeks; female) were exposed to 0.5 Gy of either γ-rays or iron radiation and control mice were sham-irradiated. Intestinal tissues were collected 2 months after radiation. DNA base lesions were measured using gas chromatography-tandem mass spectrometry with isotope‑dilution. Base excision repair (BER) and nucleotide excision repair (NER) pathways were assessed using PCR and immunoblotting. Effects of iron radiation were compared to γ-rays and sham-irradiated controls. Exposure to iron radiation resulted in significantly higher levels of several DNA base lesions relative to control animals and those exposed to γ radiation. Assessment of BER and NER showed downregulation of pathway factors both at the RNA as well as at the protein levels. Our results not only provide important insight into DNA damage pattern in intestinal cells in response to iron radiation, but they also confirm our previous immunohistochemistry data on oxidatively induced DNA damage. We suggest that downregulation of the BER and NER pathways is contributing to ongoing DNA base damages long time after radiation exposure and has implications for chronic diseases including gastrointestinal diseases after heavy ion radiation exposure during space travel.

低地球轨道外的长期太空任务将使宇航员暴露在累积剂量的高能粒子辐射下，尤其是高破坏性重离子辐射下，这对宇航员的健康构成相当大的风险。本研究的目的是定量鉴定氧化诱导的 DNA 碱基修饰，并评估在暴露于 γ 射线和铁辐射后小鼠肠细胞中去除修饰碱基所涉及的修复途径的状态。小鼠（C57BL/6J；6 至 8 周；雌性）暴露于 0.5 Gy 的 γ 射线或铁辐射，对照小鼠进行假照射。放疗后2个月收集肠组织。使用同位素稀释的气相色谱-串联质谱法测量 DNA 碱基损伤。使用 PCR 和免疫印迹评估碱基切除修复 (BER) 和核苷酸切除修复 (NER) 途径。将铁辐射的影响与 γ 射线和假辐射对照进行了比较。与对照动物和暴露于 γ 辐射的动物相比，暴露于铁辐射导致几种 DNA 碱基损伤的水平显着升高。BER 和 NER 的评估显示在 RNA 和蛋白质水平上的通路因子均下调。我们的结果不仅提供了对铁辐射反应中肠细胞 DNA 损伤模式的重要见解，而且还证实了我们之前关于氧化诱导 DNA 损伤的免疫组织化学数据。