Development of Alterations in the Lung Induced by Inhaled Silica: a Morphometric Study

Morphometric examination of lung alterations following exposure to toxic and pathogenic substances is invaluable in detecting subtle changes which might otherwise be overlooked. Results, from evaluation of initial structural alterations, support and guide subsequent nonmorphological techniques and, when coupled appropriately, can lead to a better understanding of the pathogenesis of a disease. Morphometry is a technique which can be used to determine, quantitatively, the site, extent, development, and progression of a disease state. Determination of the extent of tissue and cellular involvement in the response to inhalation of silica has been performed in order to gain a better understanding of the development of fibrosis following inhalation of this toxicant. In addition, since silica has been postulated as one of the important pathogenic minerals in coal mine dust' it is important to understand the lung tissue response to silica prior to evaluating the effects of inhaled coal mine dusts. Male Syrian golden hamsters were placed in Hazelton 1000 inhalation chambers and were exposed to either filtered air (controls, n = 24) or filtered air plus 30 mg!m3 silica (Min-U-Si110,95%ofparticles < 5 um,n =24)for16hours per day, five days per week, for two weeks. Animals were returned to the animal quarters prior to subsequent tissue processing at 1, 4, and 12 weeks following exposure. This schedule was designed to allow time for the development of fibrosis. Lungs were fixed by intratracheal perfusion of ½ strength Karnovsky's fixative at a pressure of 20 cm H20 and tissues were taken for embedment and analysis at the light level. Determination of site, extent, and development of alterations was performed using a multitiered approach. Changes in large structures (airways, blood vessels) was determined prior to evaluation of changes at the septal tissue level. Data will be presented outlining the progression of changes. Results indicate the usefulness of morphometric analysis of lungs following inhalation of toxic substances in quantitatively defining the structural alterations.