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

通过分析mRNA的表达和杂合性缺失（LOH），研究了辐射诱导小鼠肝癌的遗传变化。我们使用体外培养的原发性肝癌及其细胞系，得到了以下三个结果。1)我们尝试用差异显示技术鉴定原发性肝癌与正常肝脏的差异表达基因。发现atp酶抑制剂、核糖体蛋白L35等5个基因过表达。纤溶酶原激活剂抑制剂载脂蛋白A-IV。3-羟基-3-甲基戊二酰辅酶A （HMG-CoA）合成酶，以及UDP葡萄糖醛基转移酶-2.4-羟基苯基丙酮酸双加氧酶等3个低表达基因。和原发性肝癌中的磷脂重组酶。2)在肝癌细胞系中，我们发现在4号染色体Lci位点附近有频繁的LOH， C57BL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。其中一个是反转录转座子vl30，另一个是新分离的基因，命名为SDF-III，与SDF-II具有同源性。vl30在睾丸、卵巢和肾上腺中高表达。肝脏中vl30o mRNA的表达分析表明，在肝癌发生过程中，vl30o mRNA的表达由正常肝脏中vl30o亚群3的弱表达转变为肝癌中vl30o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，可能在蛋白质组装中起作用。研究了人类癌症中同源重组基因（RAD52上位组成员）突变的参与。我们发现RAD54的功能区域存在错义突变，并且在原发性癌症中由于异常剪接导致野生型RAD54表达缺失。此外，我们克隆了人类RALD54的同源基因，命名为RAD54B，并在原发性淋巴瘤和结肠癌中发现了RAD54B高度保守位置的纯合突变。这些发现表明，一些癌症的发生是由于同源重组基因功能的改变。少

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