Talaska G, Underwood P, Maier A, Lewtas J, Rothman N, Jaeger M
Department of Environmental Health, University of Cincinnati Medical School, Ohio 45267-0056, USA.
Environ Health Perspect. 1996 Oct;104 Suppl 5(Suppl 5):901-6. doi: 10.1289/ehp.96104s5901.
Lung cancer caused by polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs and related environmental agents is a major problem in industrialized nations. The high case-fatality rate of the disease, even with the best supportive treatment, underscores the importance of primary lung cancer prevention. Development of biomarkers of exposure and effects to PAHs and related compounds is now underway and includes measurement of urinary metabolites of specific PAHs as well as detection of protein and DNA adducts as indicators of effective dose. Validation of these markers in terms of total environmental dose requires that concurrent measures of air levels and potential dermal exposure be made. In addition, the interrelationships between PAH biomarkers must be determined, particularly when levels of the marker in surrogate molecules (e.g., protein) or markers from surrogate tissues (e.g., lymphocyte DNA) are used to assess the risk to the target organ, the lung. Two approaches to biomarker studies will be reviewed in this article: the progress made using blood lymphocytes as surrogates for lung tissues and the progress made developing noninvasive markers of carcinogen-DNA adduct levels in lung-derived cells available in bronchial-alveolar lavage and in sputum. Data are presented from studies in which exfoliated urothelial cells were used as a surrogate tissue to assess exposure to human urinary bladder carcinogens in occupational groups.
由多环芳烃(PAHs)、硝基多环芳烃及相关环境因子引起的肺癌在工业化国家是一个主要问题。即便采用最佳的支持性治疗,该病的高病死率也凸显了原发性肺癌预防的重要性。目前正在开展针对PAHs及相关化合物的暴露和效应生物标志物的研究,包括测定特定PAHs的尿代谢物以及检测蛋白质和DNA加合物作为有效剂量的指标。要根据总环境剂量对这些标志物进行验证,就需要同时测量空气水平和潜在的皮肤暴露。此外,必须确定PAH生物标志物之间的相互关系,尤其是当使用替代分子(如蛋白质)中的标志物水平或替代组织(如淋巴细胞DNA)中的标志物来评估对靶器官——肺的风险时。本文将综述生物标志物研究的两种方法:使用血淋巴细胞作为肺组织替代物所取得的进展,以及在开发支气管肺泡灌洗和痰液中可获得的肺源性细胞中致癌物-DNA加合物水平的非侵入性标志物方面所取得的进展。文中还展示了一些研究的数据,这些研究将脱落的尿路上皮细胞用作替代组织,以评估职业群体中人类膀胱致癌物的暴露情况。