Determination of genetic susceptibility factors for atmospheric toxic substances.

大气有毒物质遗传易感因素的测定。

• 批准号: 14390058
• 负责人: HIRANO Seishiro
• 金额: $ 6.91万
• 依托单位: National Institute for Environmental Studies
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14390058/
• 关键词: Oxidative stress; Glutathione; Cytotoxicity; Heme oxigenase-1; Urban particles; Arsenicals; RNA interference; Single nucleotide polymorphism; 血管内皮細胞; 細胞II型上皮細胞; 内皮細胞; cDNAアレー; ヘムオキシゲナーゼ; 抗酸化酵素; 感受性; 粒子状物質; 砒素; 肺胞II型上皮細胞

We have addressed cytotoxicity and oxidative-stress potency of organic extracts of diesel exhaust particles (OE-DEP) and urban fine particles (OE-UFP) in rat heart microvessel endothelial (RHMVE) cells. mRNA levels of antioxidant enzymes including heme oxygenase-1 (HO-1) were increased following exposure to OE-DEP and OE-UFP as well as arsenicals. It has been reported that airborne arsenicals generate from coal combustion and cause chronic arsenicism in developing countries. We investigated effects of N-acetylcysteine, buthionine sulfoximine, and siRNA fro HO-1 on cytotoxicity of OE-DEP, OE-UFP, and arsenicals in endothelial cells. N-acetylcysteine did not affect the glutathione levels and reduce the cytotoxicity of arsenicals. Buthionine sulfoximine decreased cellular glutathione level and enhanced the cytotoxicity and expression of HO-1 mRNA. Transfection with siRNA for HO-1 decreased the HO-1 RNA level and enhanced the cytotoxicity of arsenicals except for dialkylarsenicals, suggesting that HO-1 plays a role in antioxidant effects. SNP analyzes were also performed to investigate polymorphism of acetaldehyde dehydrogenase 2.

我们已经解决了柴油机尾气颗粒物（OE-DEP）和城市细颗粒物（OE-UFP）的有机提取物在大鼠心脏微血管内皮细胞（RHMVE）的细胞毒性和氧化应激效力。暴露于OE-DEP和OE-UFP以及砷剂后，包括血红素加氧酶-1（HO-1）在内的抗氧化酶的mRNA水平增加。据报道，空气中的砷来自燃煤，在发展中国家造成慢性砷中毒。我们研究了N-乙酰半胱氨酸、丁硫氨酸亚砜亚胺和针对HO-1的siRNA对OE-DEP、OE-UFP和砷剂在内皮细胞中的细胞毒性的影响。N-乙酰半胱氨酸不影响谷胱甘肽水平，并降低砷剂的细胞毒性。丁硫克百威亚砜亚胺降低细胞谷胱甘肽水平，增强细胞毒性和HO-1 mRNA表达。转染HO-1的siRNA可降低HO-1的RNA水平，增强除二烷基酚类化合物外的砷类化合物的细胞毒性，表明HO-1在抗氧化作用中起作用。SNP分析也被用来研究乙醛脱氢酶2的多态性。

项目成果

Accumulation and toxicity of monophenyl arsenicals in rat endothelial cells.

一苯砷在大鼠内皮细胞中的积累和毒性。

• 发表时间: 2005
• 期刊: Arch. Toxicol. 79
• 作者: S.Hirano;Y.Kobayashi;T.Hayakawa;X.Cui;M.Yamamoto;S.Kanno;A.Shraim
• 通讯作者: A.Shraim

S.Hirano, A.Furuyama, E.Koike, T.Kobayashi: "Oxidative-Stress Potency of Organic Extracts of Diesel Exhaust and Urban Fine Particles in Rat Heart Microvessel Endothelial Cells."Toxicolgy. 187. 161-170 (2003)

S.Hirano、A.Furuyama、E.Koike、T.Kobayashi：“大鼠心脏微血管内皮细胞中柴油机尾气和城市细颗粒有机提取物的氧化应激效力。”毒理学。

S.Hirano, H.Kitajima, T.Hayakawa, X.Cui, S.Kanno, Y.Kobayashi, M.Yamamoto: "PCR-based Subtraction Analyses for Upregulated Gene Transcription in Cadmium-exposed Rat Lung Type 2 Epithelial Cells."Biochem.Biophys.Res.Commun.. 308. 133-138 (2003)

S.Hirano、H.Kitajima、T.Hayakawa、X.Cui、S.Kanno、Y.Kobayashi、M.Yamamoto：“基于 PCR 的减法分析，对镉暴露的大鼠肺 2 型上皮细胞中基因转录上调。”

X.Cui, S.Li, A.Shraim, Y.Kobayashi, T.Hayakawa, S.Kanno, M.Yamamoto, S.Hirano: "Subchronic exposure to arsenic through drinking water alters expression of cancer-related genes in rat liver."Toxicol.Pathol.. 32. 64-72 (2003)

X.Cui、S.Li、A.Shraim、Y.Kobayashi、T.Hayakawa、S.Kanno、M.Yamamoto、S.Hirano：“通过饮用水亚慢性接触砷会改变大鼠肝脏中癌症相关基因的表达

Arsenic speciation in bile and urine following oral and intravenous exposure to inorganic and organic arsenics in rats

• DOI: 10.1093/toxsci/kfh265
• 发表时间: 2004-12-01
• 期刊: TOXICOLOGICAL SCIENCES
• 影响因子: 3.8
• 作者: Cui, X;Kobayashi, Y;Hirano, S
• 通讯作者: Hirano, S