Analysis of the mechanism of a defensive response newly found in skin epidermis to the mutagenic effect of UV.

分析皮肤表皮新发现的对紫外线致突变作用的防御反应机制。

• 批准号: 15510040
• 负责人: IKEHATA Hironobu
• 金额: $ 2.5万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15510040/
• 关键词: mutation; UV; skin; transgenic mouse; skin cancer; stratospheric ozone layer

We have found a biological response of mammalian skin to UVB that the dose-dependent mutation induction in mouse skin epidermis is suppressed at high dose range, the response that we call the mutation induction suppression (MIS). MIS response is thought to be a tissue-specific biological response that could not be deduced from cellular-level in vitro studies, and could be mediated through cell exclusion mechanisms of genomically damaged cells like apoptosis or immunological cell killing. To clarify the mechanism of MIS response, we studied the apoptotic and immunological inflammation responses in skin epidermis to UVB. However, our histological analyses have not been successful methodologically. We also performed a genetical analysis with a p53 gene-knockout mouse, and found that the p53-dependent apoptosis pathway would not contribute to MIS response.

我们已经发现哺乳动物皮肤对UVB的生物学反应，即小鼠皮肤表皮中的剂量依赖性突变诱导在高剂量范围内受到抑制，我们称之为突变诱导抑制（MIS）。MIS反应被认为是一种组织特异性生物学反应，不能从细胞水平的体外研究中推断出来，并且可以通过基因组受损细胞的细胞排斥机制（如凋亡或免疫细胞杀伤）介导。为了阐明MIS反应的机制，我们研究了皮肤表皮对UVB的细胞凋亡和免疫炎症反应。然而，我们的组织学分析在方法上并不成功。我们还对p53基因敲除小鼠进行了遗传学分析，发现p53依赖的凋亡途径不会促进MIS反应。

项目成果

Analysis of mutation spectra in UVB-exposed mouse skin epidermis and dermis:: Frequent occurrence of C→T transition at methylated CpG-associated dipyrimidine sites

• DOI: 10.1002/em.10153
• 发表时间: 2003-01-01
• 期刊: ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
• 影响因子: 2.8
• 作者: Ikehata, H;Masuda, T;Ono, T
• 通讯作者: Ono, T

UVA induces C → T transitions at methyl CpG-associated dipyrimidine sites in mouse skin epidermis more frequently than UVB.

UVA 比 UVB 更频繁地诱导小鼠皮肤表皮中甲基 CpG 相关联嘧啶位点的 C→T 转变。

• 发表时间: 2003
• 期刊: Mutagenesis 18
• 作者: Ikehata;H.;H.Kudo;T.Masuda;T.Ono
• 通讯作者: T.Ono

UVA induces C -> T transitions at methyl CpG-associated dipyrimidine sites in mouse skin epidermis more frequently than UVB.

UVA 比 UVB 更频繁地诱导小鼠皮肤表皮中甲基 CpG 相关联嘧啶位点的 C -> T 转换。

• 发表时间: 2003
• 期刊: Mutagenesis 18
• 作者: Ikehata;H.;S.Nakamura;T.Asamura;T.Ono;Hironobu Ikehata
• 通讯作者: Hironobu Ikehata

Hironobu Ikehata: "UVA induces C -> T transitions at methyl CpG-associated dipyrimidine sites in mouse skin epidermis more frequently than UVB"Mutagenesis. 18. 511-519 (2003)

Hironobu Ikehata：“UVA 比 UVB 更频繁地诱导小鼠皮肤表皮中甲基 CpG 相关二嘧啶位点的 C → T 转变”诱变。

Mutation spectrum in sunlight-exposed skin epidermis : small but appreciable contribution of oxidative stress-induced mutagenesis.

暴露在阳光下的皮肤表皮的突变谱：氧化应激诱导的突变的贡献虽小但可观。

• 发表时间: 2004
• 期刊: Mutation Research 556
• 作者: Hironobu Ikehata