In vivo experimental model for silicosis.

The selection of an experimental model for silicosis requires a thorough understanding of many pulmonary parameters specific to the experimental animal (e.g., clearance time, penetration curves, anatomical differences), as well as the strain's sensitivity to different conditions. The pulmonary response of three rat strains (i.e., Fischer 344, Sprague-Dawley, and Wistar) to silica dust was compared using two methods of exposure: intratracheal injection and inhalation. The test period lasted 3 months for injection and 6 and 12 months for inhalation. The histological study of the lung revealed a distinct nodular reaction in Sprague-Dawley and Wistar strains. Intratracheal injections led to the development of fibrotic nodules in Wistar rats, whereas such silicotic nodules were infrequent in injected Fischer 344 rats, and almost absent when exposure was by inhalation. Sprague-Dawley and Fischer 344 rats showed frequent thickening and metaplasia of the alveolar walls near the terminal bronchioles. This tendency was particularly pronounced in rats exposed by inhalation (especially Fischer 344 rats). Macroscopic examination (wet lung weight) and biochemical dosing (lung silica, hydroxyproline, and lipid content) revealed an increase in the various parameters examined in Sprague-Dawley rats relative to the other two strains, regardless of the type of exposure. The histological examination, however, leads us to conclude that the Wistar rats offer the best experimental model for silicosis, because their pulmonary reaction is more characteristic of the human condition than that of the other two strains.