Department of Molecular Biosciences, Radiation Effects Research Foundation, Hiroshima, Japan.
Department of Statistics, Radiation Effects Research Foundation, Hiroshima, Japan.
Br J Haematol. 2019 Apr;185(1):107-115. doi: 10.1111/bjh.15750. Epub 2019 Jan 13.
Enhanced inflammatory responses have been suggested decades after radiation exposure in atomic-bomb survivors, but cellular and molecular alterations related to prolonged inflammation remain unclear. This study, utilizing longitudinal haematological data over 50 years for 14 000 persons, investigated whether radiation exposure promoted the relative increase in peripheral myeloid cells, known as an aging-associated indicator of low-grade inflammation. Statistical modelling was performed with a linear mixed-effects model for leucocyte subsets, together with a proportional hazards regression model for all-cause mortality. We found that age trends in lymphocyte, neutrophil and monocyte percentages or counts differed before versus after age 60 years. Radiation dose was associated with monocyte percentages and counts, but not with the lymphoid-myeloid cell ratio. Radiation effects on monocytes were stronger after versus before age 60 years. Increases in monocyte percentages and counts were associated with higher risk of all-cause mortality. Studies of chromosomal aberrations have shown a clonal expansion of haematopoietic stem cells among atomic-bomb survivors. Therefore, radiation exposure might accelerate aging-associated clonal haematopoiesis, which could result in a long-lasting elevation of circulating monocytes.
几十年来，人们一直认为原子弹幸存者在遭受辐射后会出现增强的炎症反应，但与长期炎症相关的细胞和分子变化仍不清楚。本研究利用 14000 人长达 50 年的纵向血液学数据，调查了辐射暴露是否会促进外周髓系细胞（已知是低度炎症的与衰老相关的指标）的相对增加。使用线性混合效应模型对白细胞亚群进行统计建模，并使用全因死亡率的比例风险回归模型进行分析。我们发现，淋巴细胞、中性粒细胞和单核细胞百分比或计数的年龄趋势在 60 岁之前和之后有所不同。辐射剂量与单核细胞百分比和计数有关，但与淋巴样-髓样细胞比值无关。辐射对单核细胞的影响在 60 岁之后比之前更强。单核细胞百分比和计数的增加与全因死亡率的风险增加有关。染色体畸变研究表明，原子弹幸存者的造血干细胞存在克隆扩张。因此，辐射暴露可能会加速与衰老相关的克隆性造血，从而导致循环单核细胞的长期升高。
