van Schooten F J, Maas L M, Moonen E J, Kleinjans J C, van der Oost R
Department of Health Risk Analysis and Toxicology, University of Limburg, Maastricht, The Netherlands.
Ecotoxicol Environ Saf. 1995 Mar;30(2):171-9. doi: 10.1006/eesa.1995.1022.
A large variety of environmental carcinogens are metabolically activated to electrophilic metabolites that can bind to nucleic acids, forming covalent adducts. In organisms possessing active metabolic systems for a particular carcinogen, DNA adducts generally have longer biological half-lives than the substrate carcinogens. Thus, measurement of specific DNA adduct concentrations in terrestrial and water organisms may provide a relevant biological indicator of prior exposure to environmental carcinogens. Analysis of carcinogen load in indicator species with specific behavioral patterns may indicate human exposure risk to environmental carcinogens. Recently, sensitive assays have been developed to measure carcinogen-DNA adducts in organisms exposed to complex mixtures such as polycyclic aromatic hydrocarbons (PAH). At first instance, the nuclease P1 version of the 32P-postlabeling assay was used to examine the liver of eel (Anguilla anguilla) for the presence of aromatic DNA adducts. The fish were collected from six freshwater sites in the Amsterdam area with different levels of PAH contamination in their sediments. Chromatograms derived from DNA of fish from polluted sites revealed a broad diagonal zone indicating the presence of DNA adducts containing aromatic or bulky hydrophobic moieties not present in DNA of fish from an unpolluted reference site. Significant correlations were found between the aromatic DNA adducts levels and the levels of PAH in sediments (P < 0.001). To examine the validity of DNA adduct dosimetry in terrestrial organisms earthworms (Lumbricus terrestris) were kept on industrially contaminated PAH soils for several weeks. Several aromatic DNA adducts could be detected in DNA from the exposed earthworms; adduct levels were significantly increased with increasing exposure time.(ABSTRACT TRUNCATED AT 250 WORDS)
多种环境致癌物经代谢活化生成亲电代谢物,这些代谢物可与核酸结合,形成共价加合物。在对特定致癌物具有活跃代谢系统的生物体中,DNA加合物的生物半衰期通常比底物致癌物更长。因此,测量陆生和水生生物中特定DNA加合物的浓度,可能会提供先前接触环境致癌物的相关生物学指标。分析具有特定行为模式的指示物种中的致癌物负荷,可能表明人类接触环境致癌物的风险。最近,已开发出灵敏的检测方法来测量暴露于多环芳烃(PAH)等复杂混合物中的生物体中的致癌物-DNA加合物。首先,使用32P后标记法的核酸酶P1版本来检测鳗鱼(欧洲鳗鲡)肝脏中是否存在芳香族DNA加合物。这些鱼是从阿姆斯特丹地区的六个淡水地点收集的,其沉积物中PAH污染水平不同。来自污染地点鱼类DNA的色谱图显示出一个宽阔的对角区域,表明存在含有芳香族或庞大疏水部分的DNA加合物,而未受污染的参考地点鱼类的DNA中不存在这些加合物。发现芳香族DNA加合物水平与沉积物中PAH水平之间存在显著相关性(P < 0.001)。为了检验DNA加合物剂量测定在陆生生物蚯蚓(陆正蚓)中的有效性,将蚯蚓置于受工业污染的PAH土壤中数周。在暴露蚯蚓的DNA中可检测到几种芳香族DNA加合物;加合物水平随暴露时间的增加而显著增加。(摘要截短于250字)