Sun J D, Wolff R K, Aberman H M, McClellan R O
Toxicol Appl Pharmacol. 1983 Jun 30;69(2):185-98. doi: 10.1016/0041-008x(83)90299-5.
A large number of the environmental particulate pollutants in the atmosphere, including diesel engine exhaust, have a complex mixture of organic compounds associated with them. Organic solvent extracts of many of these particulate pollutants have been shown to contain mutagenic activity which does not require metabolic activation in the Ames bioassay. Much of this direct-acting mutagenic activity has been attributed to nitroaromatic compounds present in these extracts. In the studies reported here, the direct-acting mutagen, [3H]nitropyrene (3H-NP), was used as a model nitroaromatic compound. Rats were exposed to this radiolabeled compound by nose-only inhalation either as a coating (approximately 6% by mass) on relatively inert, ultrafine 67Ga2O3 particles or as a homogeneous ultrafine aerosol. The tissue deposition, retention, and biological fate of each aerosol were investigated and compared. Respiratory tract clearance of 3H radioactivity from each exposure was very rapid with no apparent differences seen in the lung retention of this inhaled compound between each exposure over the course of these studies. Higher 3H-radioactivity levels were seen in stomach and large intestines of rats exposed to the 67Ga2O3-associated 3H-NP than in the same tissues from rats exposed to the pure 3H-NP aerosol. Rats exposed to the 3H-NP-67Ga2O3 aerosol excreted the majority of the deposited 3H radioactivity in the feces (75 +/- 18%), whereas pure 3H-NP exposed animals excreted a major portion of the radiolabeled in the urine (76 +/- 18%). It appeared that the major portion of the pure 3H-NP aerosol was cleared from the respiratory tract by direct absorption into blood, while the 67Ga2O3-associated 3H-NP was cleared by both blood absorption and mucociliary clearance followed by ingestion and fecal excretion. These differences in the deposition and biological fate between the particle-associated NP and the pure NP aerosol may have important implications in terms of the metabolic fate of inhaled nitroaromatic compounds and the health risks associated with human exposures to particulate environmental pollutants that contain this class of compounds.
大气中的大量环境颗粒污染物，包括柴油机尾气，都伴有复杂的有机化合物混合物。许多这类颗粒污染物的有机溶剂提取物已被证明含有诱变活性，在艾姆斯生物测定中不需要代谢激活。这种直接作用的诱变活性大部分归因于这些提取物中存在的硝基芳香化合物。在本文报道的研究中，直接作用的诱变剂[3H]硝基芘（3H-NP）被用作模型硝基芳香化合物。大鼠通过仅经鼻吸入暴露于这种放射性标记化合物，它要么作为涂层（约6%质量）附着在相对惰性的超细67Ga2O3颗粒上，要么作为均匀的超细气溶胶。对每种气溶胶的组织沉积、滞留和生物学归宿进行了研究和比较。在这些研究过程中，每次暴露后3H放射性从呼吸道的清除都非常迅速，在每次暴露之间，这种吸入化合物在肺部的滞留没有明显差异。与暴露于纯3H-NP气溶胶的大鼠相比，暴露于与67Ga2O3相关的3H-NP的大鼠的胃和大肠中3H放射性水平更高。暴露于3H-NP-67Ga2O3气溶胶的大鼠将大部分沉积的3H放射性排泄到粪便中（75±18%），而暴露于纯3H-NP的动物则将大部分放射性标记物排泄到尿液中（76±18%）。似乎纯3H-NP气溶胶的大部分通过直接吸收进入血液从呼吸道清除，而与67Ga2O3相关的3H-NP则通过血液吸收和黏液纤毛清除，随后经摄入和粪便排泄而清除。颗粒结合型NP和纯NP气溶胶在沉积和生物学归宿上的这些差异，可能对吸入硝基芳香化合物的代谢归宿以及与人类接触含有这类化合物的颗粒环境污染物相关的健康风险具有重要意义。
