EXPERIMENTAL INDUCTION OF PULMONARY FIBROSIS IN SYRIAN GOLDEN-HAMSTERS BY N-METHYL-N-NITROSOURETHANE

A range finding study for experimental induction of pulmonary fibrosis in which female Syrian golden hamsters received five subcutaneous inj ections of 0.8, 0.6, 0.4, 0.2 or 0 mg of N-methyl-N-nitrosourethane (M NUR) once a week or once per two weeks revealed most of the animals of the 0.8 mg group to die of acute pulmonary injury due to MNUR while t ypical interstitial pneumonia was induced in the 0.6 mg group. Based o n these results hamsters were given five subcutaneous injections of 0. 6 mg/animal of MNUR once per two weeks and then reared without any tre atment for 12 weeks. Marked interstitial edema and intraalveolar infil tration of macrophages due to alveolar capillary damage were seen in t reated animals at week 1, and secondary diffuse fibrotic thickening of the alveolar septa, as evidenced by increased type Ill collagen demon strated immunohistochemically, was marked thereafter. The content of h ydroxyproline in the lung was significantly increased from week 4. The present study indicates that lung injuries attributable to primary da mage of alveolar capillaries progress to diffuse alveolar fibrosis in hamsters treated with MNUR, suggesting that this animal model might be of advantage for pathogenetic analysis of the relationship between pu lmonary fibrosis and lung cancer development.