Abstract

Purpose

To determine the early- and late-occurring damage in the bone marrow (BM) and peripheral blood cells of male CBA/Ca mice after exposure to 0, 0.1, 0.25, or 0.5 Gy of 1 GeV/n titanium (⁴⁸Ti) ions (one type of space radiation).

Method

We used the mouse in vivo blood-erythrocyte micronucleus (MN) assay for evaluating the cytogenetic effects of various doses of 1 GeV/n ⁴⁸Ti ions. The MN assay was coupled with the characterization of epigenetic alterations (the levels of global 5-methylcytosine and 5-hydroxymethylcytosine) in DNA samples isolated from BM cells. These analyses were performed in samples collected at an early time-point (1 week) and a late time-point (6 months) post-irradiation.

Results

Our results showed that ⁴⁸Ti ions induced genomic instability in exposed mice. Significant dose-dependent loss of global 5-hydroxymethylcytosine was found but there were no changes in global 5-methylcytosine levels.

Conclusion

Since persistent genomic instability and loss of global 5-hydroxymethylcytosine are linked to cancer, our findings suggest that exposure to ⁴⁸Ti ions may pose health risks.

中文翻译：

---

全身暴露于 1 GeV/n 48Ti 离子的雄性 CBA/Ca 小鼠骨髓细胞的早期和晚期损伤

摘要

目的

确定暴露于 0、0.1、0.25 或 0.5 Gy 的 1 GeV/n 钛 ( ⁴⁸ Ti) 离子后雄性 CBA/Ca 小鼠的骨髓 (BM) 和外周血细胞中的早期和晚期损伤（空间辐射的一种）。

方法

我们使用小鼠体内血液红细胞微核 (MN) 测定来评估不同剂量的 1 GeV/n ⁴⁸ Ti 离子的细胞遗传学效应。MN 测定与从 BM 细胞分离的 DNA 样品中的表观遗传改变（全局 5-甲基胞嘧啶和 5-羟甲基胞嘧啶的水平）的表征相结合。这些分析是在辐照后的早期时间点（1 周）和晚期时间点（6 个月）收集的样本中进行的。

结果

我们的结果表明⁴⁸ Ti 离子在暴露的小鼠中诱导基因组不稳定。发现整体 5-羟甲基胞嘧啶的显着剂量依赖性损失，但整体 5-甲基胞嘧啶水平没有变化。

结论

由于持续的基因组不稳定和整体 5-羟甲基胞嘧啶的丢失与癌症有关，我们的研究结果表明，暴露于⁴⁸ Ti 离子可能会带来健康风险。