Shimada Y, Nishimura M, Kakinuma S, Okumoto M, Shiroishi T, Clifton K H, Wakana S
Division of Low Dose Radiation and Experimental Carcinogenesis, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
Radiat Res. 2000 Sep;154(3):293-300. doi: 10.1667/0033-7587(2000)154[0293:raloha]2.0.co;2.
Although information on the molecular pathways in radiation carcinogenesis is accumulating, the data are still relatively scanty. To find the tumor suppressor locus associated with radiation carcinogenesis, we determined the frequency and distribution of loss of heterozygosity (LOH) of X-ray-induced thymic lymphomas of B6C3F(1) mice using 58 microsatellite markers and compared the results with those for spontaneous lymphomas and N-ethylnitrosourea (ENU)-induced lymphomas. Based on the results, we describe a unique locus with frequent LOH in the centromeric region of chromosome 11 of X-ray-induced lymphomas. This locus has never been observed to be altered similarly in either ENU-induced or spontaneous lymphomas, suggesting radiation-specific molecular alteration. The LOH patterns of individual thymic lymphomas indicated that the common region of LOH was located within 1.6 cM between D11Mit62 and D11Mit204, a region syntenic to human chromosome 7p13. Linkage analysis revealed that the markers of the common LOH region were genetically linked to Ikaros (now known as Znfn1a1), a master gene of lymphopoiesis. Although the presence of radiation-associated LOH in other loci cannot be ruled out, these results suggest a novel molecular pathway in induction of thymic lymphomas by ionizing radiation.
尽管关于辐射致癌分子途径的信息不断积累，但数据仍然相对较少。为了找到与辐射致癌相关的肿瘤抑制基因座，我们使用58个微卫星标记确定了B6C3F(1)小鼠X射线诱导的胸腺淋巴瘤杂合性缺失（LOH）的频率和分布，并将结果与自发淋巴瘤和N-乙基亚硝基脲（ENU）诱导的淋巴瘤进行了比较。基于这些结果，我们描述了一个在X射线诱导的淋巴瘤11号染色体着丝粒区域频繁出现LOH的独特基因座。在ENU诱导的或自发的淋巴瘤中从未观察到该基因座有类似的改变，这表明存在辐射特异性分子改变。单个胸腺淋巴瘤的LOH模式表明，LOH的共同区域位于D11Mit62和D11Mit204之间1.6 cM范围内，该区域与人类7号染色体p13区域同线。连锁分析显示，共同LOH区域的标记与淋巴细胞生成的主控基因Ikaros（现称为Znfn1a1）存在遗传连锁。尽管不能排除其他基因座存在与辐射相关的LOH，但这些结果提示了电离辐射诱导胸腺淋巴瘤的一种新的分子途径。
