Ten intratracheal instillations of N‐methyl‐N‐nitrosourea (NMU) caused squamous metaplastic and neoplastic changes in the tracheobronchial epithelium. Abnormal squamous metaplastic cells contained enlarged nuclei deeply indented by cytoplasmic invaginations, pleomorphic nucleoli, filamentous granules and many cytoplasmic fibrils. Prior to the appearance of tumors, autoradiograms revealed cells preparing for division, first in basal and then in all layers of the abnormal squamous metaplastic epithelium. Defects in the basement lamina were found in squamous metaplastic lesions. The ultrastructural changes in the tracheobronchial epithelium were similar to those described in hamsters exposed to benzo[a]pyrene‐ferric oxide as well as to those described in smoking dogs and in human bronchogenic carcinoma. The squamous metaplastic changes induced by NMU were clearly distinguishable from squamous metaplasia found in vitamin‐A deficiency.
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Harris et al. (1973) studied this question.
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