相補性下群色素性乾皮症の紫外線誘発突然変異感受性の解析

着色性干皮病互补亚群紫外线突变易感性分析

• 批准号: 06280246
• 负责人: 巽 紘一
• 金额: $ 1.34万
• 依托单位: National Institute of Radiological Sciences
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06280246/
• 关键词: 色素性乾皮症; 6チオ・グアニン抵抗性; 遺伝的相補性群; 紫外線; HPRT; DNAシーケンシング

色素性乾皮症(XP)には除去修復欠損型としてA群からG群まで7つの遺伝的相補性群がある。欧米に比し、日本ではA群とF群の患者が多い。A群と異なってF群では精神神経症状を伴わず,皮膚症状は軽く皮膚がん発症も中年以降で遅い、紫外線DNA損傷に対する修復能欠損の程度はA群XP細胞が最も強く,F群細胞では正常人細胞に比べ極めて緩徐ながら,ある程度の修復効率を示す.従って紫外線が誘発する致死損傷と発がん性突然変異誘起損傷の関係をより深く理解するために,A群XP患者,F群XP患者,正常人,の三者に由来する細胞の比較が役立つものと考えられる。特に緩徐修復が突然変異誘起損傷の固定にどのように影響するかが重要である。そこで申請者等が樹立したF群XPリンパ芽球様細胞におけるUV誘発変異頻度を調べ,これまでに観察しているA群XP,C群XP,正常人由来細胞の実験結果と比較して量的,質的差異を究明することを目指した.その結果,(1)相補性F群色素性乾皮症(XP)患者由来リンパ芽球様細胞は遠紫外線の細胞致死作用に高感受性であったが,その程度はA群細胞よりも軽く,ほぼC群細胞に近かった.(2)6チオ・グアニン抵抗性を指標とする遠紫外線誘発突然変異に対して,F群XP細胞は高感受性で,A群細胞には及ばないが,C群細胞よりも線量あたりの誘発変異頻度は高かった.(3)正常人細胞,A群XP細胞,F群XP細胞各の紫外線誘発6チオ・グアニン抵抗性変異体クローンを増殖せしめ,HPRT遺伝子cDNAを合成,PCRによる増幅の後,直接DNAシーケンシングを行って変異塩基配列の同定を開始している.

Xeroderma pigmentosum (XP) is A type of deficiency in repair that occurs in groups A and G, and a complementary type of deficiency that occurs in groups 7 and 10. In Europe, there are more patients with group A and group F than in Japan. Group A and group F showed neuropsychiatric symptoms, skin symptoms, skin symptoms, aging, and UV DNA damage. Group A XP cells were the strongest, while group F cells showed the highest recovery rate compared with normal human cells. The relationship between ultraviolet radiation induced lethal injury and sudden change of induced injury is deeply understood. The comparison of cell origin among group A XP patients, group F XP patients and normal people is conducted. Special slow repair is very important because of the damage caused by sudden change. The frequency of UV induced changes in the cells of F group XP and C group XP was adjusted, and the results of comparison between the quantitative and qualitative changes in the cells of A group XP and C group XP were investigated. Results: (1) Complementary group F xeroderma pigmentosum (XP) patients were caused by high sensitivity of cell death caused by far-ultraviolet rays in bud cells, and high sensitivity of group A cells to far-ultraviolet rays in bud cells. (2)6 F group XP cells were highly sensitive to the far-ultraviolet radiation, A group cells were highly sensitive to the far-ultraviolet radiation, and C group cells were highly sensitive to the far-ultraviolet radiation. (3)UV-induced induction in normal human cells, XP cells of group A, XP cells of group F,HPRT gene cDNA synthesis,PCR amplification, and direct DNA sequencing.