Gallagher J, George M, Kohan M, Thompson C, Shank T, Lewtas J
U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Environ Health Perspect. 1993 Mar;99:225-8. doi: 10.1289/ehp.9399225.
Development of methods to evaluate certain classes of polycyclic aromatic compounds (PAC) detected in complex mixtures to which humans are exposed would greatly improve the diagnostic potential of 32P-postlabeling analysis. Identification of DNA adduct patterns or specific exposure-related marker adducts would strengthen associations between observed DNA adducts and exposures to different environmental pollutants (e.g., kerosene, cigarette smoke, coke oven, and diesel). We have compared diesel-modified DNA adduct patterns in various in vitro and in vivo rodent model systems and compared them to DNA reactive oxidative and reductive metabolites of 1-nitropyrene. The formation of nitrated polycyclic aromatic hydrocarbon (nitrated PAH) DNA adducts, derived from the metabolism of diesel extract constituents, was enhanced relative to other PAH-derived DNA adducts via xanthine oxidase-catalyzed nitroreduction. These adducts were detectable only by the butanol extraction version of the postlabeling analysis. Five major DNA adducts were detected in human lymphocytes treated in vitro with diesel extract. A major adduct detected in human lymphocytes treated in vitro with diesel extract comigrated with a major adduct detected in lymphocyte DNA treated with benzo[a]pyrene (BaP) alone. Other adducts that co-migrated with the major BaP-derived adducts were detected in skin and lung DNA isolated from rodents topically treated with (50 mg) diesel extract and the major adduct detected in calf thymus DNA treated with rat liver S9 and diesel particle extract. Postlabeling of lung DNA isolated from rodents exposed via lung inhalation for 24 months to diesel combustion emissions resulted in the formation of a major nuclease-P1-sensitive DNA adduct that did not co-migrate with the major BaP-diol epoxide adduct.(ABSTRACT TRUNCATED AT 250 WORDS)
开发用于评估人类接触的复杂混合物中检测到的某些多环芳烃（PAC）类别的方法，将极大地提高³²P后标记分析的诊断潜力。鉴定DNA加合物模式或特定的暴露相关标记加合物，将加强观察到的DNA加合物与接触不同环境污染物（如煤油、香烟烟雾、焦炉和柴油）之间的关联。我们比较了各种体外和体内啮齿动物模型系统中柴油修饰的DNA加合物模式，并将它们与1-硝基芘的DNA反应性氧化和还原代谢物进行了比较。相对于其他多环芳烃衍生的DNA加合物，通过黄嘌呤氧化酶催化的硝基还原作用，柴油提取物成分代谢产生的硝化多环芳烃（硝化PAH）DNA加合物的形成有所增强。这些加合物只能通过后标记分析的丁醇萃取版本检测到。在用柴油提取物体外处理的人类淋巴细胞中检测到五种主要的DNA加合物。在用柴油提取物体外处理的人类淋巴细胞中检测到的一种主要加合物，与仅用苯并[a]芘（BaP）处理的淋巴细胞DNA中检测到的一种主要加合物共迁移。在用（50毫克）柴油提取物局部处理的啮齿动物分离的皮肤和肺DNA中，以及在用大鼠肝脏S9和柴油颗粒提取物处理的小牛胸腺DNA中检测到的主要加合物，与主要的BaP衍生加合物共迁移的其他加合物。对通过肺部吸入暴露于柴油燃烧排放物24个月的啮齿动物分离的肺DNA进行后标记，导致形成一种主要的核酸酶-P1敏感DNA加合物，该加合物与主要的BaP-二醇环氧化物加合物不共迁移。（摘要截短于250字）
