The Development of Carcinoma and Fibrosis in Lung of Rabbits Treated with N-methyl-N-nitrosourethane

The authors reported the development of the pulmonary fibrosis and the pulmonary carcinoma after the continous intravenous administration of N-methyl-N nitrosourethane (MNU) in the rabbits. 1. Rabbits were injected with MNU for 10 months (1mg/kg of body weight, 6 times monthly). Three of the 7 rabbits, which survived for 255 to 453 days had the development of pulmonary carcinomas. They were the subpleural rice-sized or soy-bean sized grey tumors without the infiltration or matastasis. Histologically, they were adenocarcinoma or squamous cell carcinoma. 2. Thirty-four of 36 rabbits which survived over 3 months after the administration of MNU for 4 to 10 months (1-2mg/kg of body weight, 4 to 6 times monthly) had the development of the typical diffuse interstitial fibrosis in the lung. Histologically, the developmental process of the pulmonary fibrosis through the stage of acute interstitial pneumonitis and of chronic interstitial pneumonitis was demonstrated. 3. As the histogenesis of the pulmonary carcinoma induced by MNU in rabbits, the epithelial cells in the fibrotic lesion was presumed to change into caricinoma through the glandular or squamous cells metaplasia and then the atypical proliferation. 4. In the ear of rabbits injected, 3 papillomas and 1 squamous cell carcinoma were demonstrated, although no development of tumors was observed in the liver, spleen, kidney and the other organs.