Sequential morphologic alterations in the bronchial epithelium of Syrian golden hamsters during N-nitrosomorpholine-induced pulmonary tumorigenesis

N-nitrosomorpholine (NM)-induced pulmonary carcinogenesis was examined by light and electron microscopy in a 20-week serial sacrifice study using Syrian golden hamsters. First to be observed were a proliferation of endocrine APUD cells and a formation of lamellated inclusion bodies in the cytoplasm of Clara cells. After continued NM treatment, APUD cells underwent squamous metaplasia and Clara cells invaded the pulmonary tissues adjacent to the bronchi. Lung tumors consisted of cells possessing numerous lamellated inclusion bodies in their cytoplasm and a few squamous metaplastic and APUD cells. The observed pathologic alterations closely resembled those found after treatment with N-diethylnitrosamine (DEN) and N-dibutylnitrosamine (DBN) but were completely different from the cellular reactions induced by polycyclic aromatic hydrocarbons. It is concluded that the observed alterations of APUD cells and Clara cells are specific to nitrosamines.