通过超高性能液体色谱学与高分辨率质谱学相结合,开发一种非向DNA附加学方法
Giorgia La Barbera1, Marshal Spenser Shuler1, Søren Hammershøj Beck2
1Department of Nutrition Exercise and Sports, University of Copenhagen, Frederiksberg, DK-1985, Denmark.
Talanta
|October 17, 2024
概括
研究人员开发了一种新的,敏感的方法来检测未知的DNA添加物,识别了38种新型化合物. 这种DNA adductomics方法通过揭示潜在的环境致癌物来推动癌症研究.
科学领域:
- 环境化学环境化学
- 分子毒理学分子毒理学
- 分析化学是一种分析化学.
背景情况:
- 来自各种来源的基因毒剂可以破坏DNA,可能导致癌症.
- 传统的DNA adduct分析方法是有限的,阻碍了对"DNA adductome"的全面理解.
- 使用高分辨率质谱法 (HRMS) 的DNA附加组学旨在选未知的DNA附加物,但面临敏感性和选挑战.
研究的目的:
- 开发一种敏感的,非向的DNA附加学方法,用于识别新型DNA附加物.
- 克服DNA附加学方面的分析挑战,包括敏感性和有效的选方法.
- 应用开发的方法来分析各种生物样本中的DNA附加物,包括人类结肠组织.
主要方法:
- 使用超高性能液态染色学 (UHPLC) 与电喷离子化 (ESI) 和四极时飞行质谱学 (Q-TOF MS) 相结合.
- 优化移动相 (二氧化氨酸),MS参数 (毛细管电压,圆电压,探测器电压),低吸附容器和混合表面涂层柱子.
- 采用MSE (全离子碎片化) 获取方法,通过分析脱氧和核基碎片离子的损失来选DNA添加物.
主要成果:
- 成功开发和优化了一种敏感的,非向的DNA附加组学方法.
- 在小牛胸腺,猫结肠和人类结肠DNA中暂时确定了54个DNA附加物.
- 在确定的引证中,38个是新的,代表了引证发现的重大进步.
结论:
- 开发的方法提供了高灵敏度和高效率的非向DNA adductomics.
- 这项研究代表了人类结肠组织的第一个非向的DNA附加组学分析,识别了许多新的附加组.
- 该方法对未来的人类研究有很大的前景,研究新的环境致癌物及其在癌症中的作用.
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