Claxton Larry D, Matthews Peggy P, Warren Sarah H
Cellular Toxicology Branch, Environmental Carcinogenesis Division, US Environmental Protection Agency, Research Triangle Park, NC 27709, USA.
Mutat Res. 2004 Nov;567(2-3):347-99. doi: 10.1016/j.mrrev.2004.08.002.
Mutagens in urban air pollution come from anthropogenic sources (especially combustion sources) and are products of airborne chemical reactions. Bacterial mutation tests have been used for large, multi-site, and/or time series studies, for bioassay-directed fractionation studies, for identifying the presence of specific classes of mutagens, and for doing site- or source-comparisons for relative levels of airborne mutagens. Early research recognized that although carcinogenic PAHs were present in air samples they could not account for the majority of the mutagenic activity detected. The mutagenicity of airborne particulate organics is due to at least 500 identified compounds from varying chemical classes. Bioassay-directed fractionation studies for identifying toxicants are difficult to compare because they do not identify all of the mutagens present, and both the analytical and bioassay protocols vary from study to study. However, these studies show that the majority of mutagenicity is usually associated with moderately polar/highly polar classes of compounds that tend to contain nitroaromatic compounds, aromatic amines, and aromatic ketones. Smog chamber studies have shown that mutagenic aliphatic and aromatic nitrogen-containing compounds are produced in the atmosphere when organic compounds (even non-mutagenic compounds) are exposed to nitrogen oxides and sunlight. Reactions that occur in the atmosphere, therefore, can have a profound effect on the genotoxic burden of ambient air. This review illustrates that the mutagenesis protocol and tester strains should be selected based on the design and purpose of the study and that the correlation with animal cancer bioassay results depends upon chemical class. Future emphasis needs to be placed on volatile and semi-volatile genotoxicants, and on multi-national studies that identify, quantify, and apportion mutagenicity. Initial efforts at replacing the Salmonella assay for ambient air studies with some emerging technology should be initiated.
城市空气污染中的诱变剂来自人为源(尤其是燃烧源),是大气化学反应的产物。细菌突变试验已用于大规模、多地点和/或时间序列研究、生物测定导向的分级分离研究、确定特定类别的诱变剂的存在,以及对空气中诱变剂的相对水平进行地点或来源比较。早期研究认识到,尽管空气样本中存在致癌多环芳烃,但它们并不能解释所检测到的大部分诱变活性。空气中颗粒有机物的诱变性至少归因于500种已鉴定的来自不同化学类别的化合物。用于确定有毒物质的生物测定导向的分级分离研究难以进行比较,因为它们没有识别出所有存在的诱变剂,而且分析和生物测定方案因研究而异。然而,这些研究表明,大部分诱变性通常与中等极性/高极性类别的化合物有关,这些化合物往往含有硝基芳烃、芳香胺和芳香酮。烟雾箱研究表明,当有机化合物(甚至非诱变化合物)暴露于氮氧化物和阳光时,大气中会产生诱变脂肪族和芳香族含氮化合物。因此,大气中发生的反应会对环境空气的遗传毒性负担产生深远影响。这篇综述表明,应根据研究的设计和目的选择诱变方案和测试菌株,并且与动物癌症生物测定结果的相关性取决于化学类别。未来需要重点关注挥发性和半挥发性遗传毒物,以及识别、量化和分配诱变性的跨国研究。应该开始初步努力,用一些新兴技术取代用于环境空气研究的沙门氏菌试验。