Institute of Hygiene and Occupational Medicine, University Hospital Essen, Essen, Germany.
Proteomics. 2011 Feb;11(4):644-56. doi: 10.1002/pmic.201000403. Epub 2011 Jan 18.
The simultaneous analysis of a wide array of proteins may provide valuable information on the activation and suppression of cellular systems at different stages of the exposure-disease continuum. In this review, results of proteomic studies in the field of toxicology are covered, focusing on the effects of chemical carcinogens. So far, alterations of highly abundant proteins have been identified which, irrespective of the wide differences in study design and technologies used, can be grossly assigned to three functional classes: proteins related to cellular stress response, inflammation, and stimulation of the immune system. It is obvious that the observed protein alterations are not causal factors in the development of chemically induced cancer but rather reflect common reactions to cellular perturbations. In order to gain deeper insights into the process of chemical carcinogenesis, the previously applied "shotgun" analyses have to be abandoned in favour of targeted proteomic approaches focusing on the accurate identification and quantification of selected proteins. Advanced analytical techniques such as selective reaction monitoring (SRM) and multiple reaction monitoring (MRM) offer this opportunity. If toxicoproteomic research moves into that direction and takes advantage of such techniques it will have the potential to contribute to the elucidation of chemical carcinogenesis.
同时分析大量蛋白质可能会为暴露-疾病连续体的不同阶段细胞系统的激活和抑制提供有价值的信息。在这篇综述中，涵盖了毒理学领域的蛋白质组学研究结果，重点关注化学致癌物的影响。到目前为止，已经确定了高度丰富的蛋白质的改变，这些改变无论在研究设计和使用的技术方面存在广泛差异，都可以大致分为三个功能类别：与细胞应激反应、炎症和免疫系统刺激有关的蛋白质。显然，观察到的蛋白质改变不是化学诱导癌症发展的因果因素，而是反映了对细胞扰动的常见反应。为了更深入地了解化学致癌的过程，以前应用的“鸟枪法”分析必须被放弃，转而采用靶向蛋白质组学方法，重点准确识别和定量选择的蛋白质。先进的分析技术，如选择性反应监测 (SRM) 和多重反应监测 (MRM) 提供了这种机会。如果毒蛋白组学研究朝这个方向发展并利用这些技术，它将有可能有助于阐明化学致癌作用。
