Bundeswehr Institute of Radiobiology, Munich, Germany.
Institut de Recherche Biomedicale des Armees, Bretigny-sur-Orge, France.
Radiat Res. 2019 Dec;192(6):579-588. doi: 10.1667/RR15450.1. Epub 2019 Sep 26.
In a radiation exposure event, a likely scenario may include either total-body irradiation (TBI) or different partial-body irradiation (PBI) patterns. Knowledge of the exposure pattern is expected to improve prediction of clinical outcome. We examined miRNA species in 17 irradiated baboons receiving an upper-body, left hemibody or total-body irradiation of 2.5 or 5 Gy. Blood samples were taken before irradiation and at 1, 2, 7, 28 and 75-106 days after irradiation. Using a qRT-PCR platform for simultaneous detection of 667 miRNAs, we identified 55 miRNAs over all time points. Candidate miRNAs, such as miR-17, miR-128 or miR-15b, significantly discriminated TBI from different PBI exposure patterns, and 5-to-10-fold changes in gene expression were observed among the groups. A total of 22 miRNAs (including miR-17) revealed significant linear associations of gene expression changes with the percentage of the exposed body area ( < 0.0001). All these changes were primarily observed at day 7 postirradiation and almost no miRNAs were detected either before or after 7 days. A significant association in the reduction of lymphocyte counts in TBI compared to PBI animals corresponded with the number of miRNA candidates. This finding suggests that our target miRNAs predominantly originated from irradiated lymphocytes. In summary, gene expression changes in the peripheral blood provided indications of the exposure pattern and a suggestion of the percentage of the exposed body area.
在辐射暴露事件中,可能的情况包括全身照射(TBI)或不同的半身照射(PBI)模式。对暴露模式的了解有望提高对临床结果的预测。我们研究了 17 只接受 2.5 或 5 Gy 上半身、左半身或全身照射的狒狒的 miRNA 种类。在照射前和照射后 1、2、7、28 和 75-106 天采集血样。使用 qRT-PCR 平台同时检测 667 个 miRNA,我们在所有时间点都鉴定出了 55 个 miRNA。候选 miRNA,如 miR-17、miR-128 或 miR-15b,可以区分 TBI 与不同的 PBI 暴露模式,并且在各组中观察到基因表达的 5 到 10 倍变化。总共 22 个 miRNA(包括 miR-17)显示基因表达变化与暴露身体面积的百分比呈显著线性关联(<0.0001)。所有这些变化主要发生在照射后 7 天,在 7 天之前或之后几乎检测不到任何 miRNA。与 PBI 动物相比,TBI 中淋巴细胞计数减少的显著相关性与 miRNA 候选物的数量相对应。这一发现表明,我们的靶 miRNA 主要来源于受照射的淋巴细胞。总之,外周血中的基因表达变化提供了暴露模式的指示,并提示了暴露身体面积的百分比。