中文摘要：

目的 探索α粒子照射诱发人外周血淋巴细胞双链断裂（DSB）的修复特点及与染色质结构的关系,为其作为α核素内照射鉴定指标和生物剂量估算指标提供实验依据.方法 取4名健康成人外周血淋巴细胞,0.5 Gyα粒子和γ射线照射,采用免疫荧光技术检测照射后10 min～48 h DSB分子标志物γH2AX焦点、同源重组（HR）修复蛋白Rad51焦点的形成及其消除过程,以及它们在染色质中的分布.结果 与未照射时相比,人淋巴细胞经0.5 Gyα粒子照射后10 min ～2 h,可见明显的线性γH2AX焦点径迹形成（t=ll.12、14.40、16.56,P＜0.05）,至照后6h基本消失;而γH2AX焦点形成数在α粒子照射后30 min达到最大值（t=51.72,P＜0.05）,6h内快速下降（t=29.83,P＜0.05）,至照后24 ～ 48 h残留焦点数约为16％;照后10 min,约27％的γH2AX焦点位于DAPI亮染的异染色质区,可能降低了其修复效率.而0.5 Gyγ射线照射后10 min ～48 h,未见线性γH2AX焦点径迹形成,随机、散在分布的γH2AX焦点均位于DAPI淡染的常染色质区,焦点形成数与残留数均显著低于α粒子照射诱发的焦点数.修复蛋白Rad51焦点在α粒子和γ射线照射后30min ～2 h有升高趋势,但与本底值无明显差异,且与γH2AX焦点的共定位仅占3％ ～8％.结论 α粒子照射诱发入外周血淋巴细胞线性γH2AX焦点径迹形成可作为判断是否存在α粒子内照射的生物指标,其在照射后稳定存在一定时间的特性,为其作为生物剂量估算指标提供了可能.

英文摘要：

Objective To investigate the characteristics of repair of DNA double strand breaks （DSB） induced by high-LET α-particle irradiation and their relationship with chromatin structure in the G0 lymphocytes of human peripheral blood,in order to provide the experimental basis for the judgement and dose evaluation of internal α-particle radiation.Methods Peripheral whole blood were collected from four healthy adults and lymphocytes were separated.A monocellular layer of human lymphocytes attached in Mylar film were irradiated with 0 and 0.5 Gy of α-particles and the lymphocytes suspensions were irradiated with 0 and 0.5 Gy of γ-rays.The formations of γH2AX foci as a surrogate marker of DSB and Rad51 foci as a marker of homologous recombination （HR） repair and their spatial localization in chromatin structure were measured by immunofluorescence staining technique at 10 min-48 h post-irradiation.Results Linear-γH2AX foci tracks were observe at 10 min-2 h post-irradiation in lymphocytes exposed to α-particle irradiation（t =11.12,14.40,16.56,P ＜ 0.05）,and almost completely disppeared at 6 h postirradiation.The frequencies of γH2AX foci peaked at 30 min after α-particle irradiation （t =51.72,P ＜0.05） and then decreased rapidly during 6 h post-irradiation （t =29.83,P ＜ 0.05）.The average number of foci remained only about 16％ at 24-48 h post-irradiation.Moreover,27％ of γH2AX foci located at DAPI-bright heterochromatin region at 10 min after α-particle radiation,suggesting that the efficacy of DSB repair may be decreased.In contrast,at 10 min-48 h after γ-ray irradiation,no linear γH2AX foci track was observed and the γH2AX foci diffused randomly in nucleus and predominantly located in DAPI-weak euchromatin region.The numbers of formative and residual γH2AX foci after γ-ray irradiation were significantly less than those after α-particle radiation.During 30 min-2 h after α-particle and γ-ray irradiation,the frequencies of Rad51 foci slightly but not significantly increased in comp