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体外暴露于氡及其子体后在人外周血淋巴细胞中诱导的γ-H2AX/53BP1/pKAP-1 焦点和线性轨迹。

γ-H2AX/53BP1/pKAP-1 foci and their linear tracks induced by in vitro exposure to radon and its progeny in human peripheral blood lymphocytes.

机构信息

Department of Radiation Biology, Institute of Radiation Medicine, Fudan University, Shanghai, 200032, China.

Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.

出版信息

Sci Rep. 2016 Dec 6;6:38295. doi: 10.1038/srep38295.

Abstract

The biodosimetric information is critical for evaluating the human health hazards caused by radon and its progeny. Here, we demonstrated that the formation of phosphorylated histone variant H2AX (γ-H2AX), p53-binding protein 1 (53BP1) and phosphorylated KRAB-associated protein 1 (pKAP-1) foci and their linear tracks in human peripheral blood lymphocytes (HPBLs) in vitro exposed to radon and its progeny were dependent on the cumulative absorbed dose of radon exposure but was unrelated to the concentration of radon. Among them, γ-H2AX foci and its linear tracks were the most sensitive indicators with the lowest estimable cumulative absorbed dose of 1.74 mGy from their linear dose-response curves and sustained for 12 h after termination of radon exposure. In addition, three types of foci showed an overdispersed non-Poisson distribution in HPBLs. The ratios of pKAP-1/γ-H2AX foci co-localization, 53BP1/γ-H2AX foci co-localization and 53BP1/pKAP-1 foci co-localization were significantly increased in HPBLs exposed to radon while they were unrelated to the cumulative dose of radon exposure, suggesting that γ-H2AX, pKAP-1 and 53BP1 play an important role in the repair of heterochromatic double-strand breaks. Altogether, our findings provide an experimental basis for estimating the biological dose of internal α-particle irradiation from radon and its progeny exposure in humans.

摘要

氡及其子体的生物剂量学信息对于评估氡及其子体对人类健康的危害至关重要。在这里,我们证明了体外暴露于氡及其子体的人外周血淋巴细胞(HPBL)中磷酸化组蛋白变体 H2AX(γ-H2AX)、p53 结合蛋白 1(53BP1)和磷酸化 KRAB 相关蛋白 1(pKAP-1)焦点及其线性轨迹的形成依赖于氡暴露的累积吸收剂量,但与氡浓度无关。其中,γ-H2AX 焦点及其线性轨迹是最敏感的指标,其线性剂量反应曲线的最低可估计累积吸收剂量为 1.74 mGy,在氡暴露终止后可持续 12 小时。此外,三种类型的焦点在 HPBL 中呈现出过度离散的非泊松分布。暴露于氡的 HPBL 中 pKAP-1/γ-H2AX 焦点共定位、53BP1/γ-H2AX 焦点共定位和 53BP1/pKAP-1 焦点共定位的比值显著增加,而与氡暴露的累积剂量无关,表明γ-H2AX、pKAP-1 和 53BP1 在修复异染色质双链断裂中发挥重要作用。总之,我们的研究结果为估算人类内α粒子辐射的生物剂量提供了实验依据。

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