Sequential pathological changes induced in rats with the anti-cancer drug I, 3-bis (2-chloroethyl)-I-nitrosourea...

The pathology of pulmonary toxicity induced by the anticancer drug 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) was studied in F344 rats. The compound was administered in a multiple-dose regimen comparable to the dose schedule commonly given patients. Morphological aspects were investigated by light and electron microscopy in a serial sacrifice experiment. All animals developed pulmonary fibrosis accompanied by formation of peribronchial and peribronchiolar foci of granulomatous tissue. The first morphologically detectable changes were identified in alveolar type II cells and were suggestive of disturbed surfactant synthesis. Endothelial damage accompanied by pronounced plasma cell infiltration developed subsequently and was followed by the development of diffuse interstitial fibrosis.