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MEASUREMENT OF ALKENYL/EPOXY DNA ADDUCTS BY GC-MS

通过 GC-MS 测量烯基/环氧 DNA 加合物

基本信息

批准号：
2277602
负责人：
ROGER Wallace GIESE
金额：
$ 3.23万
依托单位：
NORTHEASTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-01-01 至 1994-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2277602
关键词：
DNA adduct alkenes electrophoresis environmental toxicology epoxides gas chromatography mass spectrometry human tissue occupational health /safety

项目摘要

New analytical methodology is to be developed to measure DNA adducts arising from occupational human exposure to ethylene, ethylene oxide, butadiene, styrene and propene. These chemicals were selected since they are widely used and genotoxic. Also they are anticipated to give the same types of DNA adducts. The proposed methodology basically comprises four steps: (1) isolate the DNA from a biological sample; (2) separate the DNA adducts from the bulk of the DNA; (3) electrophore derivatize the adducts; and (4) detect the electrophoric products by gas chromatography - electron capture negative ion-mass spectrometry (GC-ECNI-MS). Electrophoric derivatization/GC-ECNI-MS has been selected because of the need for sensitive, definitive measurements. Current methodology is limited in these respects, which makes it difficult to make accurate assessments of exposure and risk. It is important to measure DNA adducts in human samples. DNA is an ultimate target in the body for carcinogenic and mutagenic chemicals. Measurements of DNA adducts can help to sort out uncertainties arising from exposure of individuals to multiple chemicals, and from individual variations in metabolism and lifestyle. Our understanding of the biological significance of chemical damage to DNA is dependent on our ability to measure it.

将开发新的分析方法来测量DNA加合物由于职业性人类暴露于乙烯，环氧乙烷，丁二烯、苯乙烯和丙烯。这些化学品是从它们被广泛使用并且具有遗传毒性。他们还预计将给予相同类型的DNA加合物。所提出的方法基本上包括四个步骤：（1）分离（2）从生物样品中分离DNA加合物; 大量的DNA;（3）电泳衍生的加合物;和（4）检测气相色谱-电子捕获电泳产物负离子质谱法（GC-ECNI-MS）。电泳的选择衍生化/GC-ECNI-MS是因为需要敏感的、明确的测量。目前的方法局限于这些方面，这使得很难作出准确的评估，暴露和风险。测量人体样本中的DNA加合物非常重要。 DNA是一种致癌和致突变化学物质在体内的最终目标。 DNA加合物的测量可以帮助解决个人暴露于多种化学品，新陈代谢和生活方式的变化。我们理解 DNA化学损伤的生物学意义取决于我们的有能力去衡量它。