Macdonald J L, Kane A B
Department of Pathology and Laboratory Medicine, Brown University School of Medicine, Providence, Rhode Island, 02912, USA.
Fundam Appl Toxicol. 1997 Aug;38(2):173-83. doi: 10.1006/faat.1997.2344.
The mesothelial lining is a target for the fibrotic and carcinogenic effects of mineral fibers. Fiber geometry, dimensions, chemical composition, surface reactivity, and biopersistence at the target tissue have been proposed to contribute to these toxic endpoints. We established a dose-response relationship between the number of fibers delivered to the parietal peritoneal lining, inflammation, and mesothelial cell proliferation induced by intraperitoneal injection of crocidolite asbestos fibers in mice. Persistence of these inflammatory and proliferative responses depended on persistence of fibers at the target tissue. Intraperitoneal injection of wollastonite fibers induced an early inflammatory and proliferative response that subsided after 21 days. Approximately 50% of wollastonite fibers were recovered by bleach digestion after 21 days and only 2% were recovered after 6 months. In contrast, the number of fibers recovered from tissue digests had not declined 6 months after injection of crocidolite asbestos. These results support the hypothesis that biopersistent fibers cause persistent inflammation and chronic mesothelial cell proliferation.
间皮衬里是矿物纤维纤维化和致癌作用的靶点。纤维的几何形状、尺寸、化学成分、表面反应性以及在靶组织中的生物持久性被认为与这些毒性终点有关。我们建立了经腹腔注射青石棉纤维后，输送至壁层腹膜衬里的纤维数量、炎症反应和间皮细胞增殖之间的剂量反应关系。这些炎症和增殖反应的持续时间取决于纤维在靶组织中的留存时间。腹腔注射硅灰石纤维会引发早期炎症和增殖反应，该反应在21天后消退。21天后，约50%的硅灰石纤维可通过漂白消化回收，6个月后仅回收2%。相比之下，注射青石棉6个月后，从组织消化物中回收的纤维数量并未减少。这些结果支持了生物持久性纤维会导致持续性炎症和慢性间皮细胞增殖这一假说。
