核事故、核战争和核恐怖活动等会导致人体α核素内污染，而且环境核素如氡及其子体α粒子内照射对人类的致癌效应倍受人们关注，其内照射生物剂量估算问题亟待解决。本项目采用免疫荧光技术和细胞流式技术，从表观遗传学上研究人外周血淋巴细胞由DSB-集簇性损伤形成的"染色质结构变化标志物IRIF"对高LET α粒子辐射品质的特异性，建立Am-241源和氡及其子体α粒子离体照射人外周血淋巴细胞的剂量-效应曲线，并比较不同能量α粒子生物效应的差别；采用氡及其子体染毒活体动物，探索α核素在体内不均匀分布情况下外周血淋巴细胞和红骨髓细胞生物剂量之间的关系并引入修正因子；试用于氡及其子体暴露的矿工进行红骨髓累积剂量估算，与物理剂量估算结果相比较，初步验证其作为高LET α粒子内照射红骨髓生物剂量估算的可行性，为大剂量α核素内照射事故人员的医学救治和低剂量α核素内照射致癌的流行病学研究提供生物剂量依据。

The health effects of internal incorporation of alpha radionuclides following human exposure in nuclear accident, nuclear wars and nuclear terrorism and from environmental radon exposure have become a world-widely concerned issue. However, the internally incorporated radionuclides constitutes a particular type of protracted irradiation and their distribution in the body is usually very uneven, which makes the estimate of biological dose very difficult and does not be solved so far in the worldwide. In recent years, convincing evidence indicates that high linear energy transfer (LET) ionizing radiation (IR) induces clustered DNA lesions, a unique class of DNA lesion and double-strand breaks (DSB) clusters increase with LET. For DNA damage, cells have evolved efficient and rapid repair responses to maintain the integrity of the genome. Sensor proteins have been shown to localize to the sites of DSB within seconds to minutes following IR exposure, and then recruit transducer proteins which provide the signals to enzymes to repair the break, resulting in the formation of microscopically visible nuclear domains named the ionizing radiation induced foci (IRIF). Evidence from recent years suggests that chromatin organization mediates the response to DNA damage and persistent IRIF may reveal an aberrant chromatin structure due to illegitimate rejoining. It is noted that the persistent IRIF is heritable to a large progeny of cells leading to the emergence of new and stable phenotypes. In this study, a dose-response curve will be established for persistent IRIF yield as a marker of permanent chromatin alteration resulting from DSB-clustered DNA lesions using immunofluorescence analysis and flow cytometry in human peripheral blood lymphocytes irradiated in vitro with Am-241 source and Rn-222 and its progeny. Whether the persistent IRIF is specific to high-LET α-particle and the differential biological effectiveness among α-particles with different energy will be investigated. The dose-response curve of persistent IRIF yield in mouse peripheral blood lymphocytes and bone marrow cells exposed to Rn-222 and its progeny will be established in vitro respectively, which may estimate the modified factor of in vivo dose between mouse's circulating lymphocytes and red bone marrow cells. The red bone marrow absorbed dose of uranium miners exposed to radon will be estimated by detecting the persistent IRIF in lymphocytes and will be compared with the dose estimated by physical dosimetric method to verify the feasibility of assessment of biological dose specific to α-emitters. Biological dosimetric information has a valuable role in the triage, diagnosis and treatment of persons incorporated with alpha radionuclides after an accident, and is important for epidemiological studies of late stochastic diseases - i.e. cancer in internal contaminated people. Furthermore, this persistent IRIF will become a new potential biomarker for health monitor of radiation workers.