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Molecular Biological Analysis of Cells and Tissues from Animals Exposed to Chemicals and Ultraviolet Rays

对暴露于化学品和紫外线的动物的细胞和组织进行分子生物学分析

基本信息

批准号：
08457115
负责人：
SUMINO Kimiaki
金额：
$ 4.86万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

The project aimed to melecularly clarify the reactions of the cells and tissues when exposed to chemicals and ultraviolet rays. We took up chloroform as a bio-hazardous chemical first and determined the transcripts in various tissues of mice exposed to chloroform. We obtained mRNA fingerprints, by using differential display method, from the organs in ICR mice intraperitoneally injected with chloroform in corn oil vehicle or corn oil vehicle alone.Compared the fingerprints, two mRNA fragments were proved to be induced by chloroform-exposure in kidney. These mRNA fragments were sequenced and identified as the parts of ADAMTS-1 (a disintegrin and metalloprotease with thrombospondin motifs-1) and endogenous MuLV (murine leukemia virus) mRNAs. Then we measured the amounts of ADAMTS-1 and MuLV mRNAs in kidney, liver and brain of mice exposed to chloroform by using quantitative RT-PCR.Interestingly, ADAMTS-1 and MuLV mRNAs increased only in kidney, but not in liver and brain. These results indicated that tissues reacted to chloroform in a tissue-specific manner. As ADAMTS-1 gene is activated by cytokines, the increase in ADAMTS-1 mRNA in kidney may be a secondary phenomenon through the cytokine systems activated by chloroform. Activation of MuLV,which may be present in the genome as provirus, in kidney gives us new clues to chloroform related-cancers. The research of other chemicals and ultraviolet rays are on the way. In conclusion, we identified kidney-specific activation of the ADAMTS-1 and MuLV genes of mice exposed to chloroform.

该项目旨在详细阐明细胞和组织在暴露于化学品和紫外线时的反应。我们首先将氯仿作为一种生物危害化学品，并确定了暴露于氯仿的小鼠各种组织中的转录物。采用差异显示技术，分别对氯仿-玉米油混合溶剂和单纯玉米油溶剂腹腔注射的ICR小鼠各器官进行了mRNA指纹图谱分析，比较了两种mRNA指纹图谱，证实了两种mRNA指纹图谱是由氯仿暴露诱导的。对这些mRNA片段进行测序，并鉴定为ADAMTS-1（一种具有血小板反应蛋白基序的去整合素和金属蛋白酶-1）和内源性MuLV（小鼠白血病病毒）mRNA的一部分。结果表明，氯仿染毒小鼠肾脏、肝脏和脑组织中ADAMTS-1和MuLV的mRNA表达均明显增加，而肝脏和脑组织中ADAMTS-1和MuLV的mRNA表达均无明显变化。这些结果表明，组织对氯仿的反应具有组织特异性。由于ADAMTS-1基因被细胞因子激活，肾脏中ADAMTS-1 mRNA的增加可能是通过氯仿激活的细胞因子系统的继发现象。MuLV可能作为前病毒存在于基因组中，其在肾脏中的激活为我们提供了氯仿相关癌症的新线索。其他化学物质和紫外线的研究正在进行中。总之，我们确定了暴露于氯仿的小鼠的ADAMTS-1和MuLV基因的肾脏特异性激活。