Development of bioassays for gaseous chemicals using air-liquid interface culture of human lung epithelial cells

利用人肺上皮细胞气液界面培养物开发气态化学物质生物测定法

基本信息

  • 批准号:
    13480163
  • 负责人:
  • 金额:
    $ 7.55万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
  • 财政年份:
    2001
  • 资助国家:
    日本
  • 起止时间:
    2001 至 2002
  • 项目状态:
    已结题

项目摘要

To establish a series of toxicitiy evaluation systems for chemicals or environmental samples in gas phase, we employed air-liquid interface culture (ALIC) of human bronchial (air way) and alveolus epithelial cells as a basic culture method, and investigated their applications to volatile organic compounds and suspended paniculate matter (SPM).First, using a human bronchial epithelial cell line, Calu-3, we developed a simple closed system for direct gas exposure, and tested the toxicity expression of Calu-3 to several organic compounds during 48 hours of loading. The toxicity in ALIC exposure was higher than that in conventional exposure in the liquid phase. The reason was largely explained by numerical estimation that chemical concentration on the cell surface in the liquid culture is lower than that in ALIC culture, in the cause of the diffusion process of molecules in the surface liquid layer. These results indicate that basic concept of the combination of ALIC of lung cells and a si … More mple closed system is promising as a testing cytotoxicrly to gaseous compounds.Second, in vivo mimicking exposure of actual SPM samples to human lung alveolar epithelia was achieved using an air-liquid interface culture of human lung alveolar A549 cells, resulting in successful observation of the toxicity in terms of the cell survivability after 48 hours exposure. In addition, an integrated use of the ALIC-based A549 cell assay for general toxicity and the EROD-based Hep G2 cell assay for PAHs was recommended to evaluate the primary toxicity of SPM. We thereby understood the permeation kinetics of SPM toxicity across the alveolar epithelia in terms of the EROD capacity of Hep G2 cells, and were able to obtain basic information on SPM toxicity in humans.Third, we developed a numerical simulation model that describes elution of chemicals initially adsorbed onto SPM samples, intake and accumulation of these chemicals into alveolus cell layer, and their final permeation to the systemic blood circulation. By focusing on the EROD activity of SPM samples, we quantified the comprehensive toxicity of the relevant samples and used these toxicitis in determining parameters involved in these numerical simulations. In addition, we extended the numerical models in actual situations that reflect low-dose and long-term exposure of SPM to humans across the very thin layer of the alveolar tissue. Less
为了建立一套化学物质或环境样品在气相中的毒性评价体系,我们采用人支气管(呼吸道)和肺泡上皮细胞的气液界面培养(ALIC)作为基本培养方法,并研究了其在挥发性有机化合物和悬浮颗粒物(SPM)中的应用。首先,利用人支气管上皮细胞系CALU-3,建立了一种简单的封闭式气体直接暴露系统,并测试了CALU-3对几种有机物的毒性表达。ALIC染毒的毒性比常规染毒的高。其原因很大程度上是由于液体培养中细胞表面的化学物质浓度低于ALIC培养中细胞表面的化学浓度,这主要是由于表面液层中分子的扩散过程所致。这些结果表明了肺细胞ALIC与a-si…结合的基本概念。其次,利用人肺泡A549细胞的气液界面培养,实现了实际SPM样品对人肺泡上皮细胞的活体模拟暴露,成功地观察了暴露48小时后细胞存活的毒性。此外,建议综合使用基于ALIC的A549细胞一般毒性实验和基于EROD的Hep G2细胞多环芳烃实验来评估SPM的初级毒性。因此,我们根据Hep G2细胞的EROD能力来了解SPM毒性在肺泡上皮细胞的渗透动力学,从而能够获得关于SPM在人体内毒性的基本信息。第三,我们建立了一个数值模拟模型,描述了SPM样品最初吸附在SPM上的化学物质的洗脱,这些化学物质在肺泡细胞层的摄取和积累,以及它们最终渗透到体循环。通过关注SPM样品的EROD活性,我们量化了相关样品的综合毒性,并利用这些毒性来确定这些数值模拟中涉及的参数。此外,我们扩展了实际情况下的数值模型,这些模型反映了低剂量和长期暴露于人类肺泡组织非常薄的一层的SPM。较少

项目成果

期刊论文数量(22)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Y.Sakai, R.Shoji, B.-S.Kim, A.Sakoda, M.Suzuki: "Cultured human-cell-based bioassays for environmental risk management"Environ.Monit.Assess. 70. 57-70 (2001)
Y.Sakai、R.Shoji、B.-S.Kim、A.Sakoda、M.Suzuki:“用于环境风险管理的基于培养人类细胞的生物测定”Environ.Monit.Assess。
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    0
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酒井康行, 迫田章義: "In vitro臓器モデルとヒト環境応答評価への利用"生産研究. 55(2). 9-15 (2003)
Yasuyuki Sakai、Akiyoshi Sakoda:“体外器官模型及其在评估人类环境反应中的应用”生产研究 55(2) (2003)。
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    0
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"New bioassay for the evaluation of SPM toxicity using cultured human alveolus cells"Bioscience & Industry. in press. (2003)
“使用培养的人肺泡细胞评估 SPM 毒性的新生物测定法”Bioscience
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  • 影响因子:
    0
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清水啓右, 富田賢吾, 鶴達郎, 酒井康行, 迫田章義: "気液界面培養を用いた浮遊粒子状物質のバイオアッセイ手法の開発"環境科学会誌. 115(6). 425-431 (2002)
Keisuke Shimizu、Kengo Tomita、Tatsuro Tsuru、Yasuyuki Sakai、Akiyoshi Sakoda:“利用气液界面培养法开发悬浮颗粒物的生物测定方法”环境科学学会杂志 115(6)。 )
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    0
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清水啓右, 酒井康行, 迫田章義: "モデル肺胞上皮を用いたSPMの新規毒性評価"バイオサイエンスとパイオインダストリー. (印刷中). (2003)
Keisuke Shimizu、Yasuyuki Sakai、Akiyoshi Sakoda:“使用模型肺泡上皮进行 SPM 的新型毒性评估”《生物科学与生物工业》(出版中)。
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    0
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SAKAI Yasuyuki其他文献

SAKAI Yasuyuki的其他文献

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{{ truncateString('SAKAI Yasuyuki', 18)}}的其他基金

Elucidation of a complex reaction mechanism of hydrocarbon fuels
阐明碳氢化合物燃料的复杂反应机理
  • 批准号:
    25820059
  • 财政年份:
    2013
  • 资助金额:
    $ 7.55万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Establishment of the methodology for design and growth of implantable pancreatic beta cell or liver cell tissues in vitro
建立体外植入性胰腺β细胞或肝细胞组织的设计和生长方法
  • 批准号:
    22246101
  • 财政年份:
    2010
  • 资助金额:
    $ 7.55万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Integrated in vit-roin vivo organization of liver tissues having a functional bile duct network
具有功能性胆管网络的肝组织的体外整合组织
  • 批准号:
    22650108
  • 财政年份:
    2010
  • 资助金额:
    $ 7.55万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
A Study on the Formation of PAHs in the Internal Combustion Engine
内燃机中PAHs形成的研究
  • 批准号:
    21760151
  • 财政年份:
    2009
  • 资助金额:
    $ 7.55万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Feasibility of implantable liver tissues having a vascular-like blood flow network
具有血管样血流网络的植入性肝组织的可行性
  • 批准号:
    19360371
  • 财政年份:
    2007
  • 资助金额:
    $ 7.55万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Development of a small-scale biohybrid simulator for human metabolism and its application as a newcytotoxicity testing system
人体新陈代谢小型生物混合模拟器的开发及其作为新型细胞毒性测试系统的应用
  • 批准号:
    13555222
  • 财政年份:
    2001
  • 资助金额:
    $ 7.55万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Development of a multi-compartment cell culture system for quantitative evaluation of chemical impacts to humans
开发多室细胞培养系统,用于定量评估化学物质对人类的影响
  • 批准号:
    11450310
  • 财政年份:
    1999
  • 资助金额:
    $ 7.55万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B).

相似海外基金

Experiments for investigating antiviral effect of Kampo formula using primary culture of human air way epithelial cells
利用人气道上皮细胞原代培养物研究汉方方抗病毒作用的实验
  • 批准号:
    17K09288
  • 财政年份:
    2017
  • 资助金额:
    $ 7.55万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
in situ Tissue Engineering and its application for air? way reconstruction
原位组织工程及其在空气中的应用?
  • 批准号:
    21249074
  • 财政年份:
    2009
  • 资助金额:
    $ 7.55万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Changes in nasal resistance and air way structure associated with orthognathic surgery.
与正颌手术相关的鼻阻力和气道结构的变化。
  • 批准号:
    05671663
  • 财政年份:
    1993
  • 资助金额:
    $ 7.55万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
Air way trapping とその発生 mechanism に関する研究
气道滞留及其发生机制研究
  • 批准号:
    56770403
  • 财政年份:
    1981
  • 资助金额:
    $ 7.55万
  • 项目类别:
    Grant-in-Aid for Encouragement of Young Scientists (A)
ショック肺発生機序におけるair-way closureの意義
气道关闭在休克肺发育机制中的意义
  • 批准号:
    X00210----977272
  • 财政年份:
    1974
  • 资助金额:
    $ 7.55万
  • 项目类别:
    Grant-in-Aid for Encouragement of Young Scientists (A)
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