Life Span and Thymic Lymphoma Incidence in High- and Low-Dose-Rate Irradiated AKR/J Mice and Commonly Expressed Genes
Life Span and Thymic Lymphoma Incidence in High- and Low-Dose-Rate Irradiated AKR/J Mice and Commonly Expressed Genes
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DOI：
10.1667/rr1946.1
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发表时间：
2010-09-01
影响因子：
3.4
通讯作者：
Kim, Hee Sun
中科院分区：
文献类型：
--
作者：
Shin, Suk Chul;Kang, Yu Mi;Kim, Hee Sun
为了评估低剂量率辐射对癌症发病率的影响，我们将AKR/J小鼠长期置于低剂量率辐射设施（Cs-137，0.07 cGy/h）中。我们比较了胸腺淋巴瘤的发病率和寿命的小鼠照射在高剂量率（Cs-137，0.8戈伊/min，总剂量为4.5戈伊）和非照射小鼠。低剂量率照射小鼠的平均寿命（243天）长于高剂量率照射小鼠（208天）和未照射小鼠（230天）（P = 0.02）。低剂量率照射组小鼠胸腺淋巴瘤发生率比未照射组和高剂量率照射组分别低10%和20%（P < 0.01）。照射后130天收集正常大小的胸腺，并进行全基因组微阵列分析。总共评估了17，625个基因。在低剂量率照射的小鼠中上调和下调基因的频率比高剂量率照射的小鼠低1.7倍和9倍。我们分析了与致癌途径相关的表达基因（DNA修复、DNA损伤信号传导途径、细胞周期、癌症通路发现者、p53信号传导途径、细胞凋亡以及T细胞和B细胞活化）。细胞凋亡（Cd 51、Fcgr 3和Pycard）和免疫相关基因（Pycard、Lilrb 3、Igh-6、Fcgr 2b和MGC 60843）在高剂量率和低剂量率照射小鼠中均被激活。结果表明，致癌细胞已被激活的细胞凋亡和免疫机制，有助于减少胸腺淋巴瘤和延长寿命。目前正在对与低剂量率受照小鼠胸腺淋巴瘤发病率有关的表达基因进行功能研究。(C)2010年，辐射研究学会
To evaluate the effect of low-dose-rate radiation on cancer incidence, we housed AKR/J mice in a long-term low-dose-rate irradiation facility (Cs-137, 0.07 cGy/h). We compared the thymic lymphoma incidence and life span with those of mice irradiated at a high dose rate (Cs-137, 0.8 Gy/min, total dose of 4.5 Gy) and nonirradiated mice. The average life span of the low-dose-rate irradiated mice (243 days) was longer than those of the high-dose-rate irradiated mice (208 days) and nonirradiated mice (230 days) (P = 0.02). The incidence of thymic lymphoma in low-dose-rate irradiated mice was lower than that in nonirradiated mice and high-dose-rate irradiated mice by 10 and 20%, respectively (P < 0.01). Normal-sized thymuses were collected 130 days after irradiation, and whole genome microarray analysis was performed. A total of 17,625 genes were assessed. Up- and down-regulated genes in low-dose-rate irradiated mice were 1.7 and 9 times less frequent than in high-dose-rate irradiated mice. We profiled expressed genes associated with carcinogenesis pathways (DNA repair, DNA damage signaling pathway, cell cycle, cancer pathway finder, p53 signaling pathway, apoptosis and T-cell and B-cell activation). Apoptosis(Cd51, Fcgr3 and Pycard) and immune- (Pycard, Lilrb3, Igh-6, Fcgr2b and MGC60843) related genes were commonly activated in both high- and low-dose-rate irradiated mice. The results suggest that carcinogenic cells have been removed by activated apoptosis and immune mechanisms, contributing to decreased thymic lymphoma and elongated life span. Functional studies for expressed genes associated with thymic lymphoma incidence in low-dose-rate exposed mice are currently under way. (C) 2010 by Radiation Research Society