Genetic analysis for cancer risk estimation of low-dose radiation exposure.

低剂量辐射暴露癌症风险评估的遗传分析。

• 批准号: 09480123
• 负责人: KAMIYA Kenji
• 金额: $ 6.53万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09480123/
• 关键词: Mouse hepatoma; SDF-II; Radiation; VL30; gene expression; RAD54; genetic instability; homologus recombination; 放射線誘発肝癌; 肝癌細胞株; U3; CAP; LOH; レトロトランスポゾン

Genetic changes of radiation-induced mouse hepatomas was studied by analyzing the expression of mRNA and loss of heterozygosity (LOH). We used primary hepatomas and it's cell lines established in-vitro, and got following three results. 1) We tried to identify genes differntially expressed in primary hepatomas compared to normal liver by using differetial display technique. we found five over-expressed genes such as ATPase inhibitor, ribosomal protein L35. plasminogen activator inhibitors apolipoprotein A-IV.and 3-hydroxy-3-metyylglutaryl coenzyme A (HMG-CoA)synthase, and three under-expressed genes such as UDP glucuronosyltransferase-2.4-hydroxyphenylpyruvate dioxygenase. and phospholipid scramblase in primary hepatomas. 2) In hepatoma cell lines, we found the frequent LOH around the locus of Lci on chromosome 4, where C57BL mouse allele was preferentiafly lost. 3) We identified over-expressed two genes in hepatoma cells grown in soft agar culture. one was retrotransposon VL3O, the oth … More er was newly isolated gene, designated SDF-III which had homology to SDF-II.VL3O was highly expressed in testis, ovary, and adrenal gland. Analysis of the expression of VL3O mRNA in liver revealed that the expression of VL3O mRNA had changed from the weak expression of VL3O subgroup 3 in normal livers to the strong expression of VL3O subgroup 1 in hepatomas during hepato-carcinogenesis. The structure of SDF- III protein indicated that this protein was chaperon protein which located in luminal of endplasmic reticulum, and might play a role for protein assembly.The involvement of mutations in homologus recombination genes, members of the RAD52 epistasis group, was studied in human cancer. We found missense mutations at functional regions of RAD54 and the absence of the wild-type RAD54 expression resulting from aberrant, splicing in primary cancers. Furthermore, we cloned human RALD54 homologue, designated RAD54B, and found homozygous mutations at highly conserved position of RAD54B in primary lymphoma and colon cancer. These findings suggest that some cancers arise through alterations of the homologus recombination gene function. Less

通过分析mRNA的表达和杂合性（LOH）的丧失，研究了辐射诱导的小鼠肝瘤的遗传变化。我们使用了原发性肝瘤，并且它的细胞系在体外建立，并遵循了三个结果。 1）我们尝试通过使用差分显示技术与正常肝脏相比，试图鉴定在原发性肝瘤中差异表达的基因。我们发现了五个过表达的基因，例如ATPase抑制剂核糖体蛋白L35。血蛋白原激活剂抑制载脂蛋白A-IV和3-羟基-3-甲基甲酰磺酰辅酶A（HMG-COA）合成酶，以及三个表达不足的基因，例如UDP谷氨酸酮酮酶-2.4-羟基甲基丙烯酰胺酶。和原发性肝瘤中的磷脂cramblase。 2）在肝瘤细胞系中，我们在4号染色体上发现了LCI基因座的经常LOH，在该染色体上，C57BL小鼠等位基因优先丢失。 3）我们在软琼脂培养物中生长的肝瘤细胞中的两个基因确定了过表达的两个基因。一个是反转座vl3o，另一个是……更新的是新近孤立的基因，称为SDF-III，与SDF-ii.vl3o同源，在睾丸，卵巢和肾上腺中高度表达。对肝脏中VL3O mRNA的表达的分析表明，VL3O mRNA的表达已从正常生命中VL3O亚组3的弱表达变为肝癌发生过程中肝癌中VL3O亚组1的强表达。 SDF-III蛋白的结构表明，该蛋白是位于终质网腔内的伴侣蛋白，并且可能对蛋白质组装起作用。突变参与同源重组基因，RAD52上位症组的成员是人类癌症的研究。我们在RAD54的功能区域发现了错义突变，并且由于异常而没有野生型RAD54表达，在原发性癌症中剪接。此外，我们克隆了人类Rald54同源物，指定为RAD54B，并在原发性淋巴瘤和结肠癌中高度构成Rad54b的位置上发现了纯合突变。这些发现表明，某些癌症是通过改变同源重组基因功能的改变而产生的。较少的

项目成果

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Miyagawa, K., et al.: "Genetic instability and cancer." Int.J.Hematol.67. 3-14 (1998)

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