Ultrastructure and Distribution of Intracellular Spicules in Rat Lung Following Chronic Tobacco Smoke Exposure<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>

Abstract

Factors that contribute to the induction of lung tumors in F344 rats by chronic tobacco smoke exposure were studied. Previous studies had shown that tobacco smoke exposures of 1-2 years duration induced only one major type of lesion involving the respiratory airways, i.e., fibrotic and cellular enlargement of peribronchiolar alveolar septa. The airway epithelium in these areas was metaplastic and in some of the lesions, the airway lining epithelium advanced out onto the surfaces of adjacent alveoli. Epithelial cells in these lesions frequently contained elongated cytoplasmic inclusions which were oriented with their long dimensions roughly in the same plane as the long axis of the cell. Macrophages contained similar but larger inclusions. Because the composition of the inclusions could be indicative of their origin, we subjected samples of treated and control lung tissues concurrently to transmission electron microscopy and energy-dispersive X-ray fluorescence spectrometry. Spectra from inclusions of macrophages indicated the presence of the elements sulfur, phosphorus, aluminum, silicon, and iron. Spectra from type II cells, however, which did not contain inclusions, showed a different elemental composition. The results suggested that spicules were present in epithelial cells throughout the airways. Minor lesions corresponding to "microinvasion" of epithelium into the lamina propria and of capillaries into the epithelial layer were also found in the trachea.