Formation of DNA adducts and mechanism of mutagenesis induced by nanomaterials

纳米材料诱导DNA加合物的形成及诱变机制

• 批准号: 23710084
• 负责人: ISHINO Kousuke
• 金额: $ 2.91万
• 依托单位: Nippon Medical School (2013)National Center of Neurology and Psychiatry (2011-2012)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23710084/
• 关键词: DNA付加体; 突然変異; ナノマテリアル; 酸化ストレス; LC-MS/MS; アダクトミクス; マグネタイト; アダクトーム解析

Nanomaterials are useful owing to their characteristic properties and are commonly used in various fields. Nanosized magnetite (MGT) is widely utilized in medicinal and industrial fields; however, their toxicological properties are not well studied. In our previous study, we found that DNA damage analyzed by the comet assay of the lungs of ICR mice intratracheally instilled with a single dose of MGT at 0.05 or 0.2 mg/animal was approximately two- to three-fold greater than that of vehicle-instilled ICR mice. In this study, a comprehensive DNA adduct analysis (DNA adductome) revealed that a broad array of DNA adducts, including etheno-dA and heptanone-etheno-dC, were produced and that most of the DNA adducts determined as the major contributors in the MGT-exposed group could be derived from inflammation. These findings suggest that inflammatory responses are probably involved in the genotoxicity induced by MGT in the lungs of mice.

纳米材料因其独特的性能而被广泛应用于各个领域。纳米磁铁矿在医药和工业领域有着广泛的应用。然而，它们的毒理学特性尚未得到很好的研究。在我们之前的研究中，我们发现单剂量MGT（0.05或0.2 mg/只）气管内灌注ICR小鼠肺部的DNA损伤比车灌ICR小鼠大2 - 3倍。在这项研究中，一项全面的DNA加合物分析（DNA加合组）显示，产生了广泛的DNA加合物，包括乙烯- da和庚酮-乙烯- dc，并且在mgt暴露组中，大多数被确定为主要贡献者的DNA加合物可能来自炎症。这些发现提示炎症反应可能参与了MGT对小鼠肺的遗传毒性。

项目成果

ナノマテリアルにより誘発されるDNA付加体の網羅的解析

纳米材料诱导DNA加合物的综合分析

• 发表时间: 2011
• 作者: Tadashi Nittami;Tetsuo Hitomi;Kanji Matsumoto;Kazuho Nakamura;Takaharu Ikeda;Yoshihiro Setoguchi;Manabu Motoori;石野孔祐
• 通讯作者: 石野孔祐

ナノマテリアルによりマウス肺に誘発されるDNA付加体の網羅的解析

纳米材料诱导小鼠肺部DNA加合物的综合分析

• 发表时间: 2011
• 作者: 蔣池勇太;松岡雅人;石野孔祐
• 通讯作者: 石野孔祐

Genotoxicity and reactive oxygen species production induced by magnetite nanoparticles in mammalian cells

• DOI: 10.2131/jts.38.503
• 发表时间: 2013-06-01
• 期刊: JOURNAL OF TOXICOLOGICAL SCIENCES
• 影响因子: 2
• 作者: Kawanishi, Masanobu;Ogo, Sayaka;Yagi, Takashi
• 通讯作者: Yagi, Takashi

ナノマテリアルによりマウス肺に誘発される DNA付加体の網羅的解析

纳米材料诱导小鼠肺部DNA加合物的综合分析

• 发表时间: 2011
• 作者: 石野孔祐;加藤竜也;戸塚ゆ加里;中釜斉
• 通讯作者: 中釜斉

A comprehensive analysis of DNAadducts in mice exposed to nanomaterials

暴露于纳米材料的小鼠 DNA 加合物的综合分析

• 发表时间: 2011
• 作者: 石野孔祐;戸塚ゆ加里;加藤竜也;中釜斉
• 通讯作者: 中釜斉