Early- and late-occurring damage in bone marrow cells of male CBA/Ca mice exposed whole-body to 1 GeV/n ⁴⁸Ti ions

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). 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. 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. 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.

本研究旨在探究雄性CBA/Ca小鼠暴露于0、0.1、0.25或0.5 Gy的1 GeV/n钛（⁴⁸Ti）离子（一种空间辐射）后，其骨髓（bone marrow, BM）和外周血细胞中早发性与迟发性损伤的变化。我们采用小鼠体内血红细胞微核（micronucleus, MN）试验，评估不同剂量1 GeV/n ⁴⁸Ti离子的细胞遗传学效应。该微核试验结合了对骨髓细胞分离所得DNA样本的表观遗传改变特征分析——即全局5-甲基胞嘧啶与5-羟甲基胞嘧啶水平的检测。上述分析分别在辐照后早期时间点（1周）与晚期时间点（6个月）采集的样本中完成。研究结果显示，⁴⁸Ti离子可诱导受辐照小鼠产生基因组不稳定性。我们观测到全局5-羟甲基胞嘧啶水平呈现显著的剂量依赖性下降，但全局5-甲基胞嘧啶水平未发生明显变化。鉴于持续性基因组不稳定性与全局5-羟甲基胞嘧啶水平下降均与癌症发生密切相关，本研究结果提示，暴露于⁴⁸Ti离子可能会对健康构成风险。

搜集汇总

背景与挑战

背景概述

该数据集研究了雄性CBA/Ca小鼠暴露于1 GeV/n钛离子后骨髓细胞的早期和晚期损伤。通过微核试验和表观遗传分析，发现钛离子诱导基因组不稳定性，并导致全局5-羟甲基胞嘧啶的剂量依赖性损失，但全局5-甲基胞嘧啶水平无变化，提示这可能与癌症风险相关。数据集由NASA资助，属于生物物理学和遗传学等领域。