Possible new complementation group of xeroderma pigmentosum

着色性干皮病可能的新互补群

• 批准号: 17591167
• 负责人: MORIWAKI Shinichi
• 金额: $ 2.24万
• 依托单位: Osaka Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591167/
• 关键词: DNA repair; DNA damage; Ultraviolet; xeroderma pigmentosum; ucomplementation group; 色素性患皮症; マイクロアレイ; 体細胞ハイブリッド

Xeroderma pigmentosum (XP) is an autosomal recessive photosensitive disease with abnormal pigmentation and an extremely high incidence of skin cancers. Cells from patients with XP are hypersensitive to killing by ultraviolet (UV), which is associated with impaired ability to repair UV-induced DNA damages. There are genetically different seven nucleotide excision repair (NER) deficient groups (A～G) and a NER proficient form (XP variant). We have been receiving more than 348clinical samples for the diagnosis of XP for these five years and 108 patients were newly diagnosed as having XP in our laboratory. Among them, we found 8 unusual Japanese XP cases. Those patients (17～55 y.o.) are not related and have mild clinical features with a few skin cancers in areas exposed to sunlight and so far any evidence for neurological abnormalities was not detected. Fibroblasts derived from those patients were hypersensitive to UV irradiation compared to cells from normal subjects and less sensitive to UV than XP-A XP-C and XP-D cells, while the levels of post-UV unscheduled DNA synthesis (UDS) in those patients were less than 30% of normal, respectively. Complementation test by cell fusion technique and a plasmid host cell reactivation assay revealed that those patients did not belong to XP group A, B, C, D, F and G. DNA repair studies and gene analysis indicated that those patients were not in XP group E and XP variant. Cell fusion analysis using those cell strains implied that there were at least two more new XP complementation groups. cDNA and miRNA microarray analyses showed the decreased expression of ATM, CLSPN and FANCD. Continuing molecular and biochemical analyses using the cells from those patients should give a new insight in NER pathway.

着色性干皮病（XP）是一种常染色体隐性遗传的光敏性疾病，具有异常的色素沉着和极高的皮肤癌发病率。XP患者的细胞对紫外线（UV）的杀伤非常敏感，这与修复UV诱导的DNA损伤的能力受损有关。存在遗传上不同的7个核苷酸切除修复（NER）缺陷型（A~G）和一个NER精通型（XP变体）。在这五年中，我们已经收到了超过348份用于诊断XP的临床样本，其中108名患者在我们的实验室中被新诊断为XP。其中，我们发现了8例不寻常的日本XP病例。年龄17~55岁。与暴露于阳光的区域的一些皮肤癌无关，具有轻微的临床特征，迄今尚未发现任何神经异常的证据。与正常受试者的细胞相比，来自这些患者的成纤维细胞对紫外线照射过敏，对紫外线的敏感性低于XP-A、XP-C和XP-D细胞，而这些患者的紫外线后非程序性DNA合成（UDS）水平分别低于正常水平的30%。用细胞融合技术和质粒宿主细胞再激活试验进行互补试验，结果表明这些患者不属于XP A、B、C、D、F和G组。DNA修复研究和基因分析表明，这些患者不是XP E组和XP变异体。使用这些细胞株的细胞融合分析暗示至少还有两个新的XP互补组。cDNA和miRNA芯片分析显示ATM、CLSPN和FANCD的表达降低。使用这些患者的细胞进行持续的分子和生物化学分析应该会对NER通路产生新的见解。

项目成果

小児看護学;皮膚疾患

小儿皮肤病护理；

• 发表时间: 2006
• 作者: Masanori Kawasaki;Yoko Ito;Haruko Yokoyama;Masazumi Arai;Genzou Takemura;Akira Hara;Yoshiro Ichiki;Hisato Takatsu;Shinya Minatogichi;Hisayochi Fujiwara;高橋幸博;森脇真一
• 通讯作者: 森脇真一

色素性乾皮症の新しい診断法

色素性干皮病的新诊断方法

• 发表时间: 2006
• 期刊: 臨床皮膚 59
• 作者: Okuyama R;Ogawa E;Nagoshi H;Yabuki M;Kurihara A;Terui T;Aiba S;Obinata M;Tagami H;Ikawa S.;森脇真一
• 通讯作者: 森脇真一

Decreased gene expression responsible for post-ultraviolet DNA repair synthesis in aging: A possible mechanism of age-related reduction in DNA repair capacity

• DOI: 10.1111/j.0022-202x.2004.23591.x
• 发表时间: 2005-02-01
• 期刊: JOURNAL OF INVESTIGATIVE DERMATOLOGY
• 影响因子: 6.5
• 作者: Takahashi, Y;Moriwaki, SI;Inoue, S
• 通讯作者: Inoue, S

Disorders of DNA repair Therapy of skin diseases pp589-595

DNA 修复障碍 皮肤病治疗 pp589-595

• 发表时间: 2010
• 作者: Moriwaki S;Kraemer RH
• 通讯作者: Kraemer RH

In the presence of ferritin, visible light induces lipid peroxidation of the porcine photoreceptor outer segment

• DOI: 10.1080/10715760600555027
• 发表时间: 2006-08-01
• 期刊: FREE RADICAL RESEARCH
• 影响因子: 3.3
• 作者: Ohishi, Kentaro;Zhang, Xiao Mei;Matsugo, Seiichi
• 通讯作者: Matsugo, Seiichi