Stinn Walter, Teredesai Ashok, Anskeit Erwin, Rustemeier Klaus, Schepers Georg, Schnell Peter, Haussmann Hans-Juergen, Carchman Richard A, Coggins Christopher R E, Reininghaus Wolf
Philip Morris Research Laboratories GmbH, Cologne, Germany.
Inhal Toxicol. 2005 Oct;17(11):549-76. doi: 10.1080/08958370591000564.
Nose-only exposure of male and female Wistar rats to a surrogate for environmental tobacco smoke, termed room-aged sidestream smoke (RASS), to diesel engine exhaust (DEE), or to filtered, fresh air (sham) was performed 6 hours/day, 7 days/week for 2 years, followed by a 6-month post-exposure period. The particulate concentrations were 3 and 10 mg/m3. Markers of inflammation in bronchoalveolar lavage showed that DEE (but not RASS) produced a dose-related and persistent inflammatory response. Lung weights were increased markedly in the DEE (but not RASS) groups and did not decrease during the 6-month post-exposure period. Bulky lung DNA adducts increased in the RASS groups, but not in the DEE groups. Cell proliferation in the lungs was unaffected by either experimental treatment. Histopathological responses in the RASS groups were minimal and almost completely reversible; lung tumors were similar in number to those seen in the sham-exposed groups. Rats exposed to DEE showed a panoply of dose-related histopathological responses: largely irreversible and in some cases progressive. Malignant and multiple tumors were seen only in the DEE groups; after 30 months, the tumor incidence (predominantly bronchiolo-alveolar adenomas) was 2% in the sham-exposed groups, 5%in the high RASS groups, and 46% in the high DEE groups (sexes combined). Our results suggest that in rats exposed to DEE, but not to RASS, the following series of events occurs: particle deposition in lungs --> lung "overload" --> pulmonary inflammation --> tumorigenesis, without a significant modifying role of cell proliferation or DNA adduct formation.
将雄性和雌性Wistar大鼠仅通过鼻腔暴露于环境烟草烟雾的替代物（称为室内陈化侧流烟雾，RASS）、柴油发动机废气（DEE）或过滤后的新鲜空气（假暴露）中，每天暴露6小时，每周7天，持续2年，随后是6个月的暴露后观察期。颗粒物浓度分别为3和10毫克/立方米。支气管肺泡灌洗中的炎症标志物显示，DEE（而非RASS）产生了剂量相关的持续性炎症反应。DEE组（而非RASS组）的肺重量显著增加，且在6个月的暴露后观察期内没有减轻。RASS组中粗大的肺DNA加合物增加，而DEE组中未增加。两种实验处理均未影响肺中的细胞增殖。RASS组的组织病理学反应轻微且几乎完全可逆；肺肿瘤数量与假暴露组相似。暴露于DEE的大鼠表现出一系列剂量相关的组织病理学反应：很大程度上不可逆，在某些情况下呈进行性发展。仅在DEE组中出现了恶性和多发性肿瘤；30个月后，假暴露组的肿瘤发生率（主要为细支气管肺泡腺瘤）为2%，高RASS组为5%，高DEE组为46%（雌雄合计）。我们的结果表明，在暴露于DEE而非RASS的大鼠中，会发生以下一系列事件：颗粒物在肺中沉积→肺“过载”→肺部炎症→肿瘤发生，细胞增殖或DNA加合物形成未起到显著的调节作用。
