Analysis of mutation induced in UV-irradiated skin

紫外线照射皮肤诱发的突变分析

• 批准号: 11680541
• 负责人: IKEHATA Hironobu
• 金额: $ 2.11万
• 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: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11680541/
• 关键词: Mutation; UV; Skin; Transgenic mouse; Skin cancer

It is important to develop an efficient and simple method for evaluation of the frequency of sunlight-induced mutation in mammalian skin because the recent increase of the ultraviolet light (UV) component of sunlight has caused significant induction of human skin carcinoma. Utilizing a bacterial lacZ gene-introduced transgenic mouse Muta^<TM>, which has been widely used for in vivo assay of induced mutations in an animal body exposed to various mutagens, we studied the induced mutations in mouse dorsal skin irradiated with three kinds of UV sources ; UVB, UVA and solar UV.We showed each source could increase efficiently and dose-dependently the frequency of the lacZ mutants in skin genome. DNA sequence changes in the lacZ gene of the mutants recovered from the irradiated skin were analyzed, and the UV-specific mutations of G : C to A : T at dipyrimidine sites were found in more than 80% of the mutant clones irrespective of the UV sources. We also detected CC to TT tandem base substitutions, which has been considered as the most representative mutation signifying UV exposure, with all UV sources. These results indicate that the animal system introduced here will be useful for the quantitative risk evaluation of skin cancer with the sunlight exposure of human skin.

重要的是要开发一种有效的和简单的方法来评估的频率在哺乳动物皮肤中的阳光诱导的突变，因为最近增加的紫外线（UV）的阳光成分已导致显着诱导人类皮肤癌。利用已广泛应用于动物体内诱变研究的细菌lacZ基因转基因小鼠穆塔^<TM>，研究了UVB、UVA和太阳紫外线对小鼠背部皮肤的诱变作用。分析了从辐照皮肤中回收的突变体的lacZ基因中的DNA序列变化，并且在超过80%的突变体克隆中发现了在二嘧啶位点处的G：C至A：T的UV特异性突变，而与UV源无关。我们还检测到CC到TT串联碱基取代，这被认为是最具代表性的突变，标志着紫外线暴露，与所有的紫外线源。这些结果表明，该动物系统将是有用的皮肤癌的定量风险评估与人类皮肤的阳光照射。

项目成果

Ono Tetsuya, et al.: "Age-associated increase of spontaneous mutant frequency and molecular nature of mutation in newborn and old lacZ-transgenic mouse."Mutation Research. 447・2. 165-177 (2000)

Ono Tetsuya 等人：“新生和老年 lacZ 转基因小鼠中自发突变频率和突变分子性质与年龄相关的增加”。突变研究 447·2（2000 年）。

Horiguchi Mieko, et al.: "UVB-Induced gpt Mutations in the Skin of gpt delta Transgenic Mice."Environmental and Molecular Mutagenesis. 34・2-3. 72-79 (1999)

Horiguchi Mieko 等人：“gpt delta 转基因小鼠皮肤中的 UVB 诱导的 gpt 突变”。环境和分子突变。34·2-79 (1999)。

Horiguchi Mieko, et al.: "UVB-Induced gpt Mutations in the Skin of gpt delta Transgenic Mice."Environmental and Molecular Mutagenesis. 34(2-3). 72-79 (1999)

Horiguchi Mieko 等人：“gpt delta 转基因小鼠皮肤中 UVB 诱导的 gpt 突变”。环境和分子突变。

Ono Tetsuya, et al.: "Age-associated increase of spontaneous mutant frequency and molecular nature of mutation in newborn and old lacZ-transgenic mouse."Mutation Research. 447(2). 165-177 (2000)

Ono Tetsuya 等人：“新生和老年 lacZ 转基因小鼠中自发突变频率和突变分子性质与年龄相关的增加。”突变研究。

Ikehata Hironobu, et al.: "Distribution of Spontaneous CpG-Associated G : C→A : T Mutations in the lacZ gene of Muta^<TM> Mice : Effects of CpG Methylation, the Sequence Context of CpG Sites, and Severity of Mutations on the Activity of the lacZ Gene Prod

Ikehata Hironobu 等人：“Muta^<TM> 小鼠 lacZ 基因中自发 CpG 相关 G : C→A : T 突变的分布：CpG 甲基化的影响、CpG 位点的序列背景和突变的严重性lacZ 基因产物的活性