Structural analysis of styrene oxide/haemoglobin adducts by mass spectrometry: identification of suitable biomarkers for human exposure evaluation

Structural analysis of styrene oxide/haemoglobin adducts by mass spectrometry: identification of suitable biomarkers for human exposure evaluation
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DOI:
10.1002/rcm.655
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发表时间:
2002-01-01
影响因子:
2
通讯作者:
Sannolo, N
Sannolo, N
中科院分区:
化学3区
文献类型:
--
作者:
Basile, A;Ferranti, P;Sannolo, N

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血红蛋白(Hb)与苯乙烯氧化物(SO),最活跃的代谢产物的工业试剂苯乙烯,在体外反应形成的加合物的结构表征,得到了通过液相色谱/电喷雾电离质谱(LC/ES-MS)分析的改性胰蛋白酶肽的人Hb链。通过基质辅助激光解吸/电离串联质谱法(MALDI-MS/MS)表征烷基化胰蛋白酶肽,鉴定人Hb对SO的反应位点。一个程序的基础上,建立了这种特性,允许Hb修改进行评估,通过监测SO/Hb加合物,使用HPLC与选择离子记录(SIR)质谱。通过这种方法,它也是可能的比较目前可用的策略,用于测量血红蛋白加合物与SO的优点和缺点。所获得的结果可以最合理地导致SO加合物的分子剂量学的优化,本文所述的分析方法可以应用于在工作场所的苯乙烯暴露的生物监测。版权所有(C)2002约翰威利父子有限公司
The structural characterisation of adducts formed by the in vitro reaction of haemoglobin (Hb) with styrene oxide (SO), the most reactive metabolite of the industrial reagent styrene, was obtained by liquid chromatography/electrospray ionisation mass spectrometry (LC/ES-MS) analysis of modified tryptic peptides of human Hb chains. The reactive sites of human Hb towards SO were identified through characterisation of alkylated tryptic peptides by matrix-assisted laser desorption/ionisation with tandem mass spectrometry (MALDI-MS/MS). A procedure was set up based on this characterisation, allowing Hb modification to be assessed by monitoring SO/Hb adducts using HPLC with selected ion recording (SIR) mass spectrometry. By this methodology it was also possible to compare advantages and disadvantages of presently available strategies for the measurement of Hb adducts with SO. The results obtained could most plausibly lead to the optimisation of molecular dosimetry of SO adducts, and the analytical procedure described herein could be applied to the biological monitoring of styrene exposure in the workplace. Copyright (C) 2002 John Wiley Sons, Ltd.