Applied Molecular Oncology and Radiation Medicine Program, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Ontario, Canada.
Radiat Res. 2010 Jan;173(1):1-9. doi: 10.1667/RR1851.1.
Accurate biodosimetry is needed to estimate radiation doses received in vivo from accidental or unwarranted radiation exposures. We investigated the use of DNA repair foci (e.g. gamma-H2AX) at late times after irradiation in vivo as a biodosimeter of initial ionizing radiation dose. Two radiosensitive strains (SCID and BALB/c) and two radioresistant strains (C57BL/6 and C3H/HeJ) were used to quantify gamma-H2AX foci in a skin tissue microarray after doses of 1 to 10 Gy at early and late times after irradiation (1 and 7 days). Using a 3D quantitative immunofluorescence microscopy analysis, we observed a dose response for gamma-H2AX foci for all strains at 30 min, 24 h and 7 days after irradiation. The numbers of residual foci were significantly different between each of the four strains and reflected the relative radiosensitivity in vivo. In comparing gamma-H2AX focus and micronucleus formation after irradiation, we also observed association between the number of micronuclei and number of foci after 1 and 7 days between radiosensitive and radioresistant strains. We conclude that 3D image analysis of gamma-H2AX in skin can be used to detect relative radiosensitivity based on late residual gamma-H2AX foci. This technique may be a useful biodosimeter to determine dose at times up to 1 week after accidental or catastrophic radiation exposure in vivo.
准确的生物剂量测定对于估计体内因意外或不必要的辐射暴露而受到的辐射剂量是必要的。我们研究了在体内照射后晚期使用 DNA 修复焦点（例如 γ-H2AX）作为初始电离辐射剂量的生物剂量计。我们使用了两个辐射敏感株（SCID 和 BALB/c）和两个辐射抗性株（C57BL/6 和 C3H/HeJ），在照射后 1 至 10 Gy 的不同时间点，在皮肤组织微阵列中定量分析 γ-H2AX 焦点。使用 3D 定量免疫荧光显微镜分析，我们观察到所有菌株在照射后 30 分钟、24 小时和 7 天的 γ-H2AX 焦点均呈现剂量反应。在 4 个菌株之间，残留焦点的数量存在显著差异，反映了体内的相对放射敏感性。在比较照射后 γ-H2AX 焦点和微核形成之间的关系时，我们还观察到在敏感株和抗性株之间，1 天和 7 天后的微核数量与焦点数量之间存在关联。我们得出结论，皮肤中 γ-H2AX 的 3D 图像分析可用于根据晚期残留 γ-H2AX 焦点来检测相对放射敏感性。这种技术可能是一种有用的生物剂量计，可用于在体内意外或灾难性辐射暴露后长达 1 周的时间内确定剂量。
