Binková B, Dobiás L, Wolff T, Srám R J
Laboratory of Genetic Ecotoxicology, Institute of Experimental Medicine, Prague, Czech Republic.
Mutat Res. 1994 May 1;307(1):355-63. doi: 10.1016/0027-5107(94)90309-3.
Coke-oven workers are occupationally exposed to emissions containing relatively high levels of polycyclic aromatic hydrocarbons. Epidemiological studies suggest that this occupational exposure may lead to an increased risk of lung cancer. To evaluate a biologically effective exposure dose in human biomonitoring studies DNA carcinogen adduct analysis is frequently used. The most readily available source of cellular DNA in these studies is white blood cells (WBC). It is questionable whether WBC are an appropriate surrogate for target tissue cells. In this study an animal model was used to examine the relationship between DNA adduct levels in target tissues and WBC as a surrogate. Rats were exposed to emissions on the top of a coke-oven battery for 24 h during simultaneous sampling of the air for chemical analysis of polycyclic aromatic hydrocarbons. 32P-Postlabeling analysis of DNA adducts in lung, heart, liver and WBC with the butanol enrichment procedure was conducted. DNA adduct profiles differ in target and non-target tissues and WBC analyzed. One major adduct was detected in the DNA from all tissues and WBC analyzed that exhibited the same chromatographic mobility as the predominant B(a)P adduct of the standard DNA sample. The highest levels of this adduct were observed in DNA from lung and heart--16.3 and 12.9 adducts/10(9) nucleotides. The elevation compared to local control animals was 6.8-fold for lung, 8.6-fold for heart, in WBC DNA 3-fold and in liver DNA only 2-fold. In DNA samples from WBC and heart mainly this major adduct was observed. In liver DNA the other four distinct spots outside the diagonal zone (DRZ) and in lung two faster-migrating adducts inside the DRZ with higher intensities were detected. Evaluating total DNA adduct levels, almost the same extent of DNA damage in lung, heart and liver was observed (46.8, 37.7 and 46.2 adducts/10(9) nucleotides; WBC only 6.7 adducts/10(9) nucleotides). Our data showed that DNA injury in target tissue cells caused by exposure to coke-oven emissions may be more significant than expected only according to DNA adduct levels in WBC.
焦炉工人职业性接触含有相对高浓度多环芳烃的排放物。流行病学研究表明,这种职业接触可能会增加患肺癌的风险。为了在人体生物监测研究中评估生物有效接触剂量,DNA致癌物加合物分析经常被使用。在这些研究中,细胞DNA最容易获得的来源是白细胞(WBC)。白细胞是否是靶组织细胞的合适替代物值得怀疑。在本研究中,使用动物模型来研究靶组织中DNA加合物水平与作为替代物的白细胞之间的关系。在对焦炉组顶部的排放物进行24小时暴露期间,同时采集空气样本用于多环芳烃的化学分析。采用丁醇富集法对肺、心脏、肝脏和白细胞中的DNA加合物进行32P后标记分析。在所分析的靶组织、非靶组织和白细胞中,DNA加合物谱不同。在所有分析的组织和白细胞的DNA中检测到一种主要加合物,其色谱迁移率与标准DNA样品的主要苯并(a)芘加合物相同。在肺和心脏的DNA中观察到这种加合物的最高水平——分别为16.3和12.9个加合物/10(9)个核苷酸。与局部对照动物相比,肺中的升高为6.8倍,心脏中为8.6倍,白细胞DNA中为3倍,肝脏DNA中仅为2倍。在白细胞和心脏的DNA样本中主要观察到这种主要加合物。在肝脏DNA中,在对角线区(DRZ)外检测到其他四个不同的斑点,在肺中,在DRZ内检测到两个迁移速度更快、强度更高的加合物。评估总的DNA加合物水平时,在肺、心脏和肝脏中观察到几乎相同程度的DNA损伤(分别为46.8、37.7和46.2个加合物/10(9)个核苷酸;白细胞仅为6.7个加合物/10(9)个核苷酸)。我们的数据表明,接触焦炉排放物导致的靶组织细胞中的DNA损伤可能比仅根据白细胞中的DNA加合物水平所预期的更显著。