Chem Res Toxicol. 2018 Aug 20;31(8):680-687. doi: 10.1021/acs.chemrestox.8b00035. Epub 2018 Jul 17.
1-Nitropyrene (1NP) level is closely associated with the mutagenicity of diesel exhaust and is being used as the marker molecule for diesel exhaust. Thus, quantitation of the exposure to 1NP may provide an efficient method for biomonitoring human exposure to diesel exhaust and risk assessment. Using ultra-performance liquid chromatography coupled with fluorescence or tandem mass spectrometric detection methods, we quantitated and compared in this study the DNA and protein adducts of 1NP in internal organs of 1NP-exposed rats. While previous studies using radioactivity-based detection methods were descriptive in nature and focused on the mutation-associated genetic materials, the results of our quantitative analysis showed, for the first time, a significantly higher concentration of the protein adduct than the DNA adduct in the tissue samples. The data also revealed higher in vivo stability of the protein adduct than that of the DNA adduct. Our results provide solid evidence that demonstrates that the protein adduct might be a more-sensitive dosimeter for 1-NP and, thus, diesel-exhaust exposure.
1- 硝基芘 (1NP) 水平与柴油废气的致突变性密切相关,并且被用作柴油废气的标记分子。因此,1NP 的暴露量的定量可能为生物监测人体接触柴油废气和风险评估提供一种有效的方法。本研究使用超高效液相色谱法结合荧光或串联质谱检测方法,定量并比较了 1NP 暴露大鼠内部器官中 1NP 的 DNA 和蛋白质加合物。虽然以前使用基于放射性的检测方法的研究具有描述性,并且侧重于与突变相关的遗传物质,但我们的定量分析结果首次显示,在组织样本中,蛋白质加合物的浓度明显高于 DNA 加合物。该数据还揭示了蛋白质加合物比 DNA 加合物具有更高的体内稳定性。我们的结果提供了确凿的证据,证明蛋白质加合物可能是 1-NP 和因此柴油废气暴露的更敏感的剂量计。