Taylor-McCabe Kirsten J, Wang Zaolin, Sauer Nancy N, Marrone Babetta L
Bioscience Division, MS M888, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Proteomics. 2006 Mar;6(5):1663-75. doi: 10.1002/pmic.200500190.
Beryllium is the second lightest metal, has a high melting point and high strength-to-weight ratio, and is chemically stable. These unique chemical characteristics make beryllium metal an ideal choice as a component material for a wide variety of applications in aerospace, defense, nuclear weapons, and industry. However, inhalation of beryllium dust or fumes induces significant health effects, including chronic beryllium disease and lung cancer. In this study, the mutagenicity of beryllium sulfate (BeSO(4)) and the comutagenicity of beryllium with a known mutagen 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) were evaluated using a forward mutant detection system developed in Escherichia coli. In this system, BeSO(4) was shown to be weakly mutagenic alone and significantly enhanced the mutagenicity of MNNG up to 3.5-fold over MNNG alone. Based on these results a proteomic study was conducted to identify the proteins regulated by BeSO(4). Using the techniques of 2-DE and oMALDI-TOF MS, we successfully identified 32 proteins being differentially regulated by beryllium and/or MNNG in the E. coli test system. This is the first study to describe the proteins regulated by beryllium in vitro, and the results suggest several potential pathways for the focus of further research into the mechanisms underlying beryllium-induced genotoxicity.
铍是第二轻的金属，具有高熔点和高强度重量比，且化学性质稳定。这些独特的化学特性使铍金属成为航空航天、国防、核武器及工业等广泛应用中组件材料的理想选择。然而，吸入铍尘或铍烟会引发严重的健康问题，包括慢性铍病和肺癌。在本研究中，使用在大肠杆菌中开发的正向突变检测系统评估了硫酸铍（BeSO₄）的致突变性以及铍与已知诱变剂1-甲基-3-硝基-1-亚硝基胍（MNNG）的共诱变作用。在该系统中，硫酸铍单独显示出弱致突变性，并且将MNNG的致突变性显著增强至单独使用MNNG时的3.5倍。基于这些结果进行了一项蛋白质组学研究，以鉴定受硫酸铍调控的蛋白质。使用二维电泳（2-DE）和基质辅助激光解吸电离飞行时间质谱（oMALDI-TOF MS）技术，我们成功鉴定出在大肠杆菌测试系统中受铍和/或MNNG差异调控的32种蛋白质。这是第一项描述铍在体外调控蛋白质的研究，结果提示了几个潜在途径，可作为进一步研究铍诱导遗传毒性机制的重点。
