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

通过对辐射诱发小鼠肝癌的基因表达和杂合性丢失（洛）分析，研究了辐射诱发小鼠肝癌的遗传学变化。本实验采用体外建立的肝癌细胞系和原代肝癌细胞，得到以下三个结果。1)我们尝试用荧光显示技术来鉴定原发性肝癌与正常肝组织中差异表达的基因。发现了ATP酶抑制剂、核糖体蛋白L35等5个基因的过表达。纤溶酶原激活物抑制剂载脂蛋白A-IV和3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）合酶，以及三个低表达基因，如UDP葡萄糖醛酸转移酶-2，4-羟苯基丙酮酸双加氧酶。和磷脂爬行酶。2)在肝癌细胞系中，我们发现在4号染色体Lci位点附近存在频繁的洛缺失，其中C57 BL小鼠等位基因优先丢失。3)我们在软琼脂培养的肝癌细胞中发现了两个过表达的基因。逆转录转座子VL 30、VL 30 ...更多信息 er是新分离的基因，命名为SDF-Ⅲ，与SDF-Ⅱ具有同源性。结果表明，在肝癌发生过程中，肝组织中VL 3 OmRNA的表达由正常肝组织中VL 3 O亚群3的弱表达转变为肝癌组织中VL 3 O亚群1的强表达。SDF-III蛋白的结构表明该蛋白是位于内质网腔内的伴侣蛋白，可能在蛋白组装中起作用。我们发现错义突变的功能区域的RAD 54和野生型RAD 54表达的情况下，导致异常，剪接在原发性癌症。此外，我们克隆了人RALD 54同源物，命名为RAD 54 B，并在原发性淋巴瘤和结肠癌中发现RAD 54 B高度保守位置的纯合突变。这些发现表明，一些癌症是通过同源重组基因功能的改变而产生的。少

项目成果

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Patek, C.E. 等人：“小鼠 WR1 的锌指截断会导致 Denys-Drash 综合征的特征性泌尿生殖系统异常。”

Hosoya, N., et al.: "Mutation analysis of the WT1 gene in myelodysplastic syndromes." Jpn.J.Cancer Res.89. 821-824 (1998)

Hosoya, N. 等人：“骨髓增生异常综合征中 WT1 基因的突变分析。”

Miyagawa, K., et al.: "Mutations of the WT1 gene in childhood non-lymphoid hematological malignancies." Genes Chromo.Cancer. (in press).

Miyakawa, K. 等人：“儿童非淋巴血液恶性肿瘤中 WT1 基因的突变。”

Kamiya,K.,et al.: "Quantitative studies of ductal versus alveolar differentiation from rat mammary clonogens." Proc.Soc.Exp.Biol.Med.,. 219. 217-225 (1998)

Kamiya,K.,et al.：“大鼠乳腺克隆原的导管与肺泡分化的定量研究。”

天野 隆、その他: "B6C3F1マウスでの自然発生肝癌と放射線誘発肝癌の遺伝子変異スペクトラムの比較" 広島医学. 51. 407-410 (1998)

Takashi Amano 等人：“B6C3F1 小鼠自发性肝癌和辐射诱发肝癌的基因突变谱的比较”Hiroshima Medical。51. 407-410 (1998)