Gelzleichter T R, Bermudez E, Mangum J B, Wong B A, Janszen D B, Moss O R, Everitt J I
Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709, USA.
Toxicol Sci. 1999 May;49(1):93-101. doi: 10.1093/toxsci/49.1.93.
The present study was designed to determine whether pleural fiber burdens or subchronic pleural fibroproliferative and inflammatory changes can help explain the marked interspecies differences in pleural fibrosis and mesothelioma that are observed following long-term inhalation of RCF-1 ceramic fibers by rats and hamsters. Fischer 344 rats and Syrian golden hamsters were exposed to RCF-1 for 4 h per day, 5 days per week, for 12 consecutive weeks. Lung and pleural fiber burdens were characterized during and after exposure. For all time points, approximately 67% of fibers associated with lung tissues from both rats and hamsters were longer than 5 microns in length. In comparison, fibers longer than 5 microns recovered from the pleural compartment, following a 12-week exposure and 12 weeks of recovery, accounted for 13% (hamsters) and 4% (rats) of the distribution. In the 12 weeks after the cessation of exposure, the number of fibers longer than 5 microns in length remained constant in the hamster at approximately 150 fibers per cm2 pleura. This was 2 to 3 times the corresponding fiber surface density in the rat. Significant pulmonary and pleural inflammation was detected at all time points and for both species. DNA synthesis by pleural mesothelial cells was quantified by bromodeoxyuridine uptake following 3 days of labeling. Labeling indices were higher in hamsters than in rats, both for RCF-1-exposed and filtered air-control animals and was highest for the parietal surface of the pleura. Significantly greater collagen deposition was measured in the visceral pleura of hamsters 12 weeks post-exposure but was not significantly elevated in rats. These findings demonstrate that subchronic inhalation exposure to RCF-1 induces pleural inflammation, mesothelial-cell turnover, pleural fibrosis, and an accumulation of fibers with a length greater than 5 microns in the hamster. The accumulation of long fibers in the pleural space may contribute to the pathology observed in the hamster following chronic inhalation of RCF-1, whereas the presence of short, thin fibers may play a role in the acute-phase biological response seen in both species.
本研究旨在确定胸膜纤维负荷或亚慢性胸膜纤维增生和炎症变化是否有助于解释大鼠和仓鼠长期吸入RCF - 1陶瓷纤维后观察到的胸膜纤维化和间皮瘤在种间的显著差异。将Fischer 344大鼠和叙利亚金黄仓鼠每天暴露于RCF - 1中4小时，每周5天，连续12周。在暴露期间和暴露后对肺和胸膜纤维负荷进行表征。对于所有时间点，与大鼠和仓鼠肺组织相关的纤维中约67%长度超过5微米。相比之下，在12周暴露和12周恢复后，从胸膜腔回收的长度超过5微米的纤维分别占分布的13%（仓鼠）和4%（大鼠）。在暴露停止后的12周内，仓鼠胸膜中长度超过5微米的纤维数量保持恒定，约为每平方厘米胸膜150根纤维。这是大鼠相应纤维表面密度的2至3倍。在所有时间点对两个物种均检测到显著的肺部和胸膜炎症。通过3天标记后的溴脱氧尿苷摄取对胸膜间皮细胞的DNA合成进行定量。对于暴露于RCF - 1的动物和过滤空气对照动物，仓鼠的标记指数均高于大鼠，且在胸膜的壁层表面最高。暴露后12周，在仓鼠的脏层胸膜中测量到显著更多的胶原蛋白沉积，但在大鼠中未显著升高。这些发现表明，亚慢性吸入暴露于RCF - 1会诱导仓鼠胸膜炎症、间皮细胞更新、胸膜纤维化以及长度大于5微米的纤维积累。胸膜腔中长纤维的积累可能导致仓鼠在慢性吸入RCF - 1后出现的病理变化，而短而细的纤维的存在可能在两个物种中观察到的急性期生物学反应中起作用。
