Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA.
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA.
J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Jun 15;1087-1088:49-60. doi: 10.1016/j.jchromb.2018.04.041. Epub 2018 Apr 24.
4-Aminobiphenyl (4-ABP) which is primarily formed during tobacco combustion and overheated meat is a major carcinogen responsible for various cancers. Its adducted form, N-deoxyguanosine-C8-4-aminobiphenyl (dG-C8-4-ABP), has long been employed as a biomarker for assessment of the risk for cancer. In this review, the metabolism and carcinogenisity of 4-ABP will be discussed, followed by a discussion of the current common approaches of analyzing dG-C8-4-ABP. The major part of this review will be on the history and recent development of key methods for detection and quantitation of dG-C8-4-ABP in complex biological samples and their biological applications, from the traditional P-postlabelling and immunoassay methods to modern liquid chromatography-mass spectrometry (LC-MS) with the latter as the focus. Many vital biological discoveries based on dG-C8-4-ABP have been published by using the nanoLC-MS with column switching platform in our laboratory, which has also been adopted and further improved by many other researchers. We hope this review can provide a perspective of the challenges that had to be addressed in reaching our present goals and possibly bring new ideas for those who are still working on the frontline of DNA adducts area.
4-氨基联苯（4-ABP）主要在烟草燃烧和过热肉类中形成，是导致各种癌症的主要致癌物。其加合物形式，脱氧鸟苷-C8-4-氨基联苯（dG-C8-4-ABP），长期以来一直被用作评估癌症风险的生物标志物。在这篇综述中，将讨论 4-ABP 的代谢和致癌性，然后讨论分析 dG-C8-4-ABP 的当前常用方法。这篇综述的主要部分将介绍检测和定量复杂生物样品中 dG-C8-4-ABP 的关键方法的历史和最新发展，从传统的 P-后标记和免疫测定方法到现代液相色谱-质谱联用（LC-MS），重点介绍后者。我们实验室使用带有柱切换平台的纳升液相色谱-质谱联用技术发表了许多基于 dG-C8-4-ABP 的重要生物学发现，该技术也被许多其他研究人员采用和进一步改进。我们希望这篇综述可以为实现我们目前目标所面临的挑战提供一个视角，并为那些仍在 DNA 加合物领域前沿工作的人带来新的思路。
