Respiratory tract responses to repeated inhalation of an oxidant and acid gas-particle air pollutant mixture
Respiratory tract responses to repeated inhalation of an oxidant and acid gas-particle air pollutant mixture
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DOI：
10.1093/toxsci/61.2.331
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发表时间：
2001-06-01
影响因子：
3.8
通讯作者：
Phalen, RF
中科院分区：
文献类型：
--
作者：
Mautz, WJ;Kleinman, MT;Phalen, RF
本研究的目的是检查大鼠暴露于多组分污染物大气中的广泛毒理学反应。在Fisher 344 N大鼠中检查了对3种浓度的吸入颗粒-氧化剂混合物的累积和适应性呼吸道反应，暴露4小时/天，3天/周，持续4周。混合物中含有O-3、NO2、NH 4 HSO 4、碳颗粒和HNO 3蒸气。刺激诱导的，快速浅呼吸反应存在于第一个4小时暴露于中等和高浓度。连续暴露显示中等浓度的反应减弱，高浓度的反应加剧。在4周结束时，暴露于高浓度的大鼠出现肺部病变。灌洗的肺巨噬细胞表现出Fc受体结合和吞噬作用的剂量依赖性抑制。肺组织巨噬细胞显示酸性磷酸酶染色密度和碳颗粒呈剂量依赖性增加。呼吸道对示踪粒子的清除率不受暴露的影响，高浓度的暴露可增加支气管肺泡上皮细胞的通透性。上皮细胞增殖标记显示，在呼吸道的所有水平的剂量依赖性增加。在高浓度下进行性加重的呼吸模式反应与肺部病变和鼻移行上皮和终末细支气管中的高细胞增殖标记相关。在呼吸功能受到较小但在许多情况下仍然显着损害的情况下，会发生减弱或适应性呼吸模式反应。在其他呼吸功能和肺组织损伤存在显著剂量依赖性损害的情况下，可能发生减弱或加剧的呼吸模式反应。
The purpose of this study was to examine a broad range of toxicologic responses in rats exposed to a multi-component pollutant atmosphere. Cumulative and adaptive respiratory tract responses to 3 concentrations of an inhaled particle-oxidant mixture were examined in Fisher 344 N rats exposed 4 h/day, 3 days/week for 4 weeks. The mixtures contained O-3, NO2, NH4HSO4, carbon particles, and HNO3, vapor. Irritant-induced, rapid-shallow breathing responses were present during the first 4-h exposure to medium and high concentrations. Successive exposures showed diminished responses in medium concentrations and exacerbated responses in high concentrations. At the end of 4 weeks, rats exposed to high concentrations exhibited lung lesions. Lavaged pulmonary macrophages showed dose-dependent depressions of Fc-receptor binding and phagocytosis. Lung tissue macrophages showed dose-dependent increases in acid phosphatase staining density and carbon particles. Respiratory tract clearance of tracer particles was not significantly affected by the exposures, Bronchoalveolar epithelial permeability was increased by the high concentration. Epithelial cell-proliferation labeling showed a dose-dependent increase at all levels of the respiratory tract. Progressively exacerbated breathing-pattern responses at high concentrations were associated with lung lesions and high cell-proliferation labeling in the nose transitional epithelium and terminal bronchioles. Attenuating or adaptive breathing-pattern responses occurred in the presence of smaller, but in many cases still significant, compromise of respiratory functions. Either attenuating or exacerbated breathing-pattern responses can occur in the presence of a significant dose-dependent compromise of other respiratory functions and lung tissue injury.