Mouse strains exhibit different susceptibilities to gamma-ray-induced thymic lymphomas. Our previous study identified Mtf-1 (metal responsive transcription factor-1) as a candidate susceptibility gene, which is involved in the radiation-induced signaling pathway that regulates the cellular reactive oxygen species (ROS). To reveal the mechanism for the increased susceptibility conferred by Mtf-1 locus, we examined early effects of gamma-ray on ROS levels in vivo and its difference between Mtf-1 susceptible and resistant congenic mice. Here, we show the detection of clonally growing thymocytes at 4 weeks after irradiation, indicating the start of clonal expansion at a very early stage. We also show that large thymocytes with higher ROS levels and a proliferation capacity were more numerous in the Mtf-1 susceptible mice than the resistant mice when examined at 7 days after irradiation, although such tendency was not found in mice lacking one allele of Bcl11b tumor suppressor gene. This high retention of the large thymocytes, at a high risk for ROS-induced mutation, is a compensatory proliferation and regeneration response to depletion of the thymocytes after irradiation and the response is likely to augment the development of prelymphoma cells leading to thymic lymphomas.

译文

小鼠品系对 γ射线诱导的胸腺淋巴瘤表现出不同的敏感性。我们先前的研究将Mtf-1 (金属响应转录因子-1) 确定为候选易感基因,该基因参与调节细胞活性氧 (ROS) 的辐射诱导信号传导途径。为了揭示Mtf-1基因座赋予敏感性增加的机制,我们研究了伽马射线对体内ROS水平的早期影响及其在Mtf-1易感和抗性同基因小鼠之间的差异。在这里,我们显示了照射后4周检测到克隆生长的胸腺细胞,表明克隆扩增在很早的阶段就开始了。我们还显示,在照射后7天检查时,在Mtf-1易感小鼠中,具有较高ROS水平和增殖能力的大胸腺细胞比抗性小鼠更多,尽管在缺乏Bcl11b肿瘤抑制基因一个等位基因的小鼠中未发现这种趋势。大胸腺细胞的这种高保留,具有ROS诱导的突变的高风险,是对照射后胸腺细胞耗竭的代偿性增殖和再生反应,并且该反应可能会增加导致胸腺淋巴瘤的淋巴瘤前细胞的发育。

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