BACKGROUND Micronuclei (MN), nuclear bud (NBud), and nucleoplasmic bridge (NPB) are suggested as biomarkers for radiation exposure; however, they have not been extensively studied to understand the underlying mechanisms responsible for their formation. OBJECTIVES To (1) validate NBud and NPB within the cytokinesis-blocked micronucleus (CBMN) assay as biomarkers for radiation exposure and (2) determine the effects of the DNA repair inhibitors, cytosine arabinoside (Ara C) and 3-aminobenzamide (3-AB) on radiation-induced MN, NBud, and NPB formation. METHODS Human blood samples were irradiated with 0-3 Gy X-rays and subsequently treated with Ara C and 3-AB. CBMN and chromosome aberration assays were carried out to measure MN, NBud, and NPB and dicentric chromosomes, respectively. RESULTS The frequency of radiation-induced MN, NBud, and NPB increased in a dose-dependent manner. The frequency of MN, NBud, and NPB was highly and positively correlated with the dicentric chromosome, a standard biomarker for biodosimetry (r > 0.98, p < 0.0001). Furthermore, Ara C increased the frequency of MN, NBud, and NPB, whereas 3-AB increased the frequency of MN and NPB, but not NBud. Further, the potentiating effect of Ara C on the frequency of MN, NBud, and NPB was greater than that of 3-AB. CONCLUSION Our results validate NBuds and NPBs as independent valuable markers of radiation exposure. Additionally, we suggest that different mechanisms are likely involved in the formation of NBuds and NPBs following X-irradiation; however, additional studies are warranted to better understand the contribution of distinct DNA repair pathways to the formation of radiation-induced damages.

中文翻译：

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DNA修复抑制剂阿糖胞苷和3-氨基苯甲酰胺对辐射诱导的微核，核芽和核质桥的频率的影响。

背景技术微核（MN），核芽（NBud）和核质桥（NPB）被建议作为辐射暴露的生物标志物。但是，尚未对它们进行广泛研究以了解造成其形成的潜在机制。目的（1）验证胞质分裂阻滞微核（CBMN）分析中的NBud和NPB作为辐射暴露的生物标志物，以及（2）确定DNA修复抑制剂，胞嘧啶阿拉伯糖苷（Ara C）和3-氨基苯甲酰胺（3- AB）关于辐射诱导的MN，NBud和NPB的形成。方法用0-3 Gy X射线照射人体血样，然后用Ara C和3-AB处理。进行CBMN和染色体畸变分析分别测量MN，NBud和NPB以及双中心染色体。结果辐射诱发的MN，NBud，而NPB以剂量依赖性方式增加。MN，NBud和NPB的频率与双中心染色体（生物剂量学的标准生物标志物）高度相关且呈正相关（r> 0.98，p <0.0001）。此外，Ara C增加了MN，NBud和NPB的频率，而3-AB增加了MN和NPB的频率，但不增加NBud。此外，Ara C对MN，NBud和NPB频率的增强作用大于3-AB。结论我们的结果验证了NBuds和NPBs是辐射暴露的独立有价值的标志物。此外，我们建议在X射线照射后NBuds和NPBs的形成可能涉及不同的机制。但是，有必要进行更多的研究，以更好地理解不同的DNA修复途径对辐射诱导的损伤形成的影响。