Vermeulen Roel, Lan Qing, Zhang Luoping, Gunn Laura, McCarthy Diane, Woodbury Ronald L, McGuire Marielena, Podust Vladimir N, Li Guilan, Chatterjee Nilanjan, Mu Ruidong, Yin Songnian, Rothman Nathaniel, Smith Martyn T
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 6120 Executive Boulevard, Rockville, MD 20852, USA.
Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17041-6. doi: 10.1073/pnas.0508573102. Epub 2005 Nov 14.
Benzene is an important industrial chemical and environmental contaminant that causes leukemia. To obtain mechanistic insight into benzene's mechanism of action, we examined the impact of benzene on the human serum proteome in a study of exposed healthy shoe-factory workers and unexposed controls. Two sequential studies were performed, each using sera from 10 workers exposed to benzene (overall mean benzene air level >30 ppm) and 10 controls. Serum samples were subjected to anion-exchange fractionation and bound to three types of ProteinChip arrays (Ciphergen Biosystems, Fremont, CA) [hydrophobic (H50), metal affinity (IMAC3-Cu), and cation exchange (WCX2)]. Protein-expression patterns were detected by surface-enhanced laser desorption/ionization (SELDI)-TOF MS. Three proteins (4.1, 7.7, and 9.3 kDa) were consistently down-regulated in exposed compared with control subjects in both studies. All proteins were highly inversely correlated with individual estimates of benzene exposure (r > 0.75). The 7.7- and 9.3-kDa proteins were subsequently identified as platelet factor (PF)4 and connective tissue activating peptide (CTAP)-III. Initial proteomic results for PF4 and CTAP-III were subsequently confirmed in a single experiment using a ProteinChip-array-based immunoassay(Ciphergen Biosystems). The altered expression of the platelet-derived CXC-chemokines (40% and 63% for PF4 and CTAP-III, respectively) could not be explained by changes in absolute platelet counts. Thus, SELDI-TOF analysis of a limited number of exposed and unexposed subjects revealed that lowered expression of PF4 and CTAP-III proteins is a potential biomarker of benzene's early biologic effects and may play a role in the immunosuppressive effects of benzene.
苯是一种重要的工业化学品和环境污染物，可引发白血病。为深入了解苯的作用机制，我们在一项针对接触苯的健康鞋厂工人和未接触苯的对照组的研究中，考察了苯对人血清蛋白质组的影响。我们进行了两项连续的研究，每项研究均使用了10名接触苯的工人（苯在空气中的总体平均水平>30 ppm）和10名对照组人员的血清。血清样本经过阴离子交换分级分离，并与三种类型的蛋白质芯片阵列（Ciphergen Biosystems公司，加利福尼亚州弗里蒙特）[疏水型（H50）、金属亲和型（IMAC3 - Cu）和阳离子交换型（WCX2）]相结合。通过表面增强激光解吸/电离（SELDI）-TOF质谱检测蛋白质表达模式。在两项研究中，与对照组相比，接触组中三种蛋白质（4.1、7.7和9.3 kDa）的表达持续下调。所有蛋白质与苯接触的个体估计值均呈高度负相关（r>0.75）。随后，7.7 kDa和9.3 kDa的蛋白质被鉴定为血小板因子（PF）4和结缔组织激活肽（CTAP）-III。PF4和CTAP-III的初步蛋白质组学结果随后在一项使用基于蛋白质芯片阵列的免疫测定法（Ciphergen Biosystems公司）的单一实验中得到了证实。血小板衍生的CXC趋化因子（PF4和CTAP-III分别为40%和63%）表达的改变无法用血小板绝对计数的变化来解释。因此，对有限数量的接触组和未接触组受试者进行的SELDI-TOF分析表明，PF4和CTAP-III蛋白质表达降低是苯早期生物学效应的潜在生物标志物，可能在苯的免疫抑制作用中发挥作用。
