Everitt J I, Gelzleichter T R, Bermudez E, Mangum J B, Wong B A, Janszen D B, Moss O R
Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709, USA.
Environ Health Perspect. 1997 Sep;105 Suppl 5(Suppl 5):1209-13. doi: 10.1289/ehp.97105s51209.
In the present subchronic study, we compared pleural inflammation, visceral pleural collagen deposition, and visceral and parietal pleural mesothelial cell proliferation in rats and hamsters identically exposed to a kaolin-based refractory ceramic fiber, (RCF)-1 by nose-only inhalation exposure, and correlated the results to translocation of fibers to the pleural cavity. Fischer 344 rats and Syrian golden hamsters were exposed to 650 fibers/cc of RCF-1, for 4 hr/day, 5 days/week for 12 weeks. Following 4 and 12 weeks of exposure, and after a 12-week recovery period, pleural lavage fluid was analyzed for cytologic and biochemical evidence of inflammation. Visceral and parietal pleural mesothelial cell proliferation was assessed by immunocytochemical detection of bromodeoxyuridine incorporation. Pleural collagen was quantitated using morphometric analysis of lung sections stained with Sirius Red. Fiber-exposed rats and hamsters had qualitatively similar pleural inflammation at each time point. Mesothelial cell proliferation was more pronounced in hamsters than in rats at each time point and at each site. In both species, the mesothelial cell labeling index was highest in the parietal pleural mesothelial cells lining the surface of the diaphragm at each time point. Hamsters but not rats had significantly elevated collagen in the visceral pleura at the 12-week postexposure time point. Fibers were found in the pleural cavities of both species at each time point. These fibers were generally short and thin. These results suggest that mesothelial cell proliferation and fibroproliferative changes in the pleura of rodents following short-term inhalation exposure are associated with fiber translocation to the pleura and may be predictive of chronic pleural disease outcomes following long-term exposure.
在本亚慢性研究中,我们比较了通过仅经鼻吸入暴露相同剂量的基于高岭土的难熔陶瓷纤维(RCF)-1的大鼠和仓鼠的胸膜炎症、脏层胸膜胶原沉积以及脏层和壁层胸膜间皮细胞增殖情况,并将结果与纤维向胸膜腔的转运相关联。将Fischer 344大鼠和叙利亚金黄仓鼠暴露于650根/立方厘米的RCF-1,每天4小时,每周5天,共12周。在暴露4周和12周后以及12周恢复期后,分析胸腔灌洗液中的炎症细胞学和生化证据。通过免疫细胞化学检测溴脱氧尿苷掺入来评估脏层和壁层胸膜间皮细胞增殖。使用天狼星红染色的肺切片形态计量分析对胸膜胶原进行定量。在每个时间点,纤维暴露的大鼠和仓鼠的胸膜炎症在性质上相似。在每个时间点和每个部位,仓鼠的间皮细胞增殖比大鼠更明显。在两个物种中,每个时间点在膈肌表面的壁层胸膜间皮细胞中的间皮细胞标记指数最高。在暴露后12周时间点,仓鼠而非大鼠的脏层胸膜胶原显著升高。在每个时间点,在两个物种的胸膜腔中均发现纤维。这些纤维通常短而细。这些结果表明,短期吸入暴露后啮齿动物胸膜中的间皮细胞增殖和纤维增生性变化与纤维向胸膜的转运有关,并且可能预测长期暴露后的慢性胸膜疾病结局。