Radiobiology for Children's Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555, Japan.
Radiat Res. 2014 Mar;181(3):302-13. doi: 10.1667/RR13466. Epub 2014 Feb 25.
Age at exposure is a critical factor that influences the risk of radiation-induced leukemia, which arises from hematopoietic stem and progenitor cells. However, little is known about the effect of age on the radiation response of these cells. In this study, we examined the radiation response of hematopoietic stem and progenitor cells in infant (1-week-old), juvenile (3-week-old), and adult (8- and 14-week-old) C3H/He mice, which are susceptible to radiation-induced myeloid leukemia. We first observed an age-dependent increase in the radioresistance of hematopoietic stem and progenitor cells after in vivo irradiation. However, in vitro irradiation of progenitor cells did not show any age differences, suggesting that radiation sensitivity in vivo is dependent on the bone marrow microenvironment rather than to intrinsic properties of progenitors themselves. Expression profiles of bone marrow tissues identified chemokine and cytokine family genes, whose expression differed between infant and adult tissues at time points before and after irradiation. Among the selected thirteen cytokines reported to be radioprotective, we observed increased expression of Csf1, Csf2, Cxcl12, Fgf1, Fgf7, Il1a, Il1b and Kitl after irradiation, mostly in adult tissues. Specifically, Csf2, Fgf1 and Il1b expression, as revealed by qPCR, were significantly enhanced in adult bone marrow tissue after irradiation, but were unresponsive to irradiation in infant tissue. These results suggest that the higher susceptibility of infant hematopoietic stem and progenitor cells to the cell killing effect of ionizing radiation may be attributed to a failure to induce a subset of radioprotective cytokines in the immature bone marrow microenvironment.
暴露年龄是影响辐射诱导白血病风险的关键因素，这种白血病源于造血干细胞和祖细胞。然而，对于年龄对这些细胞辐射反应的影响知之甚少。在这项研究中，我们研究了易患辐射诱导髓性白血病的 C3H/He 幼鼠（1 周龄）、幼鼠（3 周龄）和成年鼠（8 周龄和 14 周龄）造血干细胞和祖细胞的辐射反应。我们首先观察到体内照射后造血干细胞和祖细胞的放射抗性随年龄增长而增加。然而，祖细胞的体外照射没有显示出任何年龄差异，这表明体内的辐射敏感性取决于骨髓微环境，而不是祖细胞本身的内在特性。骨髓组织的表达谱确定了趋化因子和细胞因子家族基因，这些基因在照射前后的幼鼠和成年鼠组织中表达不同。在报告具有放射保护作用的十三种细胞因子中，我们观察到 Csf1、Csf2、Cxcl12、Fgf1、Fgf7、Il1a、Il1b 和 Kitl 在照射后表达增加，主要在成年组织中。具体而言，qPCR 显示，Csf2、Fgf1 和 Il1b 的表达在照射后明显增强，但在幼鼠组织中对照射无反应。这些结果表明，婴儿造血干细胞和祖细胞对电离辐射的细胞杀伤作用更敏感，这可能归因于未在未成熟的骨髓微环境中诱导一组放射保护细胞因子。
