DNA adducts: Mass spectrometry methods and future prospects

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• 作者：P.B. Farmer ; K. Brown ; E. Tompkins ; V.L. Emms ; D.J.L. Jones ; R. Singh ; D.H. Phillips
• 关键词：Mass spectrometry ; DNA adduct ; Acrylamide ; [¹⁴C]-Postlabelling ; Oxidative damage
• 刊名：Toxicology and Applied Pharmacology
• 出版年：2005
• 出版时间：1 September 2005
• 年：2005
• 卷：207
• 期：2, Supplement 1
• 页码：293-301
• 全文大小：348 K

文摘

Detection of DNA adducts is widely used for the monitoring of exposure to genotoxic carcinogens. Knowledge of the nature and amounts of DNA adducts formed in vivo also gives valuable information regarding the mutational effects that may result from particular exposures. The power of mass spectrometry (MS) to achieve qualitative and quantitative analyses of human DNA adducts has increased greatly in recent years with the development of improved chromatographic interfaces and ionisation sources. Adducts have been detected on nucleic acid bases, 2′-deoxynucleosides or 2′-deoxynucleotides, with LC-MS/MS being the favoured technique for many of these analyses. Our current applications of this technique include the determination of N7-(2-carbamoyl-2-hydroxyethyl)-guanine, which was postulated to be found as a DNA repair product in urine following exposure to acrylamide, and of 8-oxo-7,8-dihydro-2′-deoxyguanosine and 8-oxo-7,8-dihydro-2′-deoxyadenosine, as markers of oxidative damage in human lymphocyte DNA. Higher sensitivity (with a detection limit of 1–10 adducts/10¹² nucleotides) may be achieved by the use of accelerator mass spectrometry (AMS), although this requires the presence of certain isotopes, such as [¹⁴C], in the material being analysed. In order to make this technique more amenable for studies of human exposure to environmental carcinogens, new postlabelling techniques, incorporating [¹⁴C] into specific DNA adducts after formation, are being developed. It is expected that combining the use of advanced MS techniques with existing ³²P-postlabelling and immunochemical methodologies will contribute greatly to the understanding of the burden of human exposure to environmental carcinogens.