Amati Monica, Tomasetti Marco, Mariotti Laura, Tarquini Lucia Miria, Valentino Matteo, Santarelli Lory
Department of Molecular Pathology and Innovative Therapies, Institute of Occupational Medicine, Polytechnic University of Marche, Ancona, Italy.
Mutat Res. 2008 Aug-Sep;655(1-2):52-8. doi: 10.1016/j.mrgentox.2008.06.011.
Epidemiological studies have shown that mortality from malignant mesothelioma (MM) and lung cancer have increased with increasing cumulative exposure to asbestos. To investigate whether tumour-related biomarkers can contribute towards the evaluation of the carcinogenic risk in populations exposed to asbestos, the DNA adduct 8-hydroxy-2'-deoxyguanosine (80HdG), interleukine-6 (IL-6), platelet-derived growth factor (PDGF-BB), hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGFbeta) and soluble mesothelin-related peptides (SMRPs) were analysed in a cohort of workers differently exposed to asbestos fibres at the workplace. To document biomarker levels in an unexposed population, 54 age-matched subjects were enrolled. A total of 119 subjects with a history of occupational exposure to asbestos underwent clinical examination and were interviewed by trained personnel, responding to a detailed questionnaire related to duration of asbestos exposure, smoking, and occupational task. According to the occupational tasks, asbestos-exposed subjects were analysed for their asbestos cumulative dose and the association with the biomarkers was evaluated. Among the occupational groups, maintenance workers, pipe fitters and electricians were exposed to a higher cumulative dose of asbestos fibres. Exposure to asbestos significantly increased the steady-state content of 80HdG in DNA. Elevated levels of 80HdG and IL-6 best reflected a high level of SMRPs, which is related to cell transformation. Subjects heavily exposed to asbestos [> 60(ff/cm3) x years] showed also a higher level of angiogenic factors. A combination of angiogenic biomarkers with a specific mesothelioma-biomarker such as SMRPs could be used for close surveillance of workers with a history of asbestos exposure.
流行病学研究表明,恶性间皮瘤(MM)和肺癌的死亡率随着石棉累积暴露量的增加而上升。为了研究肿瘤相关生物标志物是否有助于评估石棉暴露人群的致癌风险,对一组在工作场所接触不同剂量石棉纤维的工人进行了DNA加合物8-羟基-2'-脱氧鸟苷(8-OHdG)、白细胞介素-6(IL-6)、血小板衍生生长因子(PDGF-BB)、肝细胞生长因子(HGF)、碱性成纤维细胞生长因子(bFGF)、血管内皮生长因子(VEGFβ)和可溶性间皮素相关肽(SMRP)的分析。为记录未暴露人群的生物标志物水平,招募了54名年龄匹配的受试者。共有119名有职业性石棉暴露史的受试者接受了临床检查,并由经过培训的人员进行访谈,他们回答了一份与石棉暴露持续时间、吸烟和职业任务相关的详细问卷。根据职业任务,分析石棉暴露受试者的石棉累积剂量,并评估其与生物标志物的关联。在职业组中,维修工人、管道安装工和电工接触的石棉纤维累积剂量较高。石棉暴露显著增加了DNA中8-OHdG的稳态含量。8-OHdG和IL-6水平升高最能反映与细胞转化相关的SMRP的高水平。重度石棉暴露[>60(纤维/立方厘米)×年]的受试者血管生成因子水平也较高。血管生成生物标志物与特定的间皮瘤生物标志物(如SMRP)联合使用,可用于对有石棉暴露史的工人进行密切监测。