RELATIONSHIP BETWEEN PULMONARY FIBROSIS AND LUNG PROLIFERATIVE LESIONS INDUCED BY DIFFERENT DOSES OF N-METHYL-N-NITROSOURETHANE IN SYRIAN GOLDEN HAMSTERS

• Published in: Journal of Toxicologic Pathology Vol. 9; no. 4; pp. 315 - 322
• Main Authors: Yasuhara, Kazuo, Mitsumori, Kunitoshi, Yoshimura, Hiroyuki, Imazawa, Takayoshi, Onodera, Hiroshi, Takegawa, Kiyoshi, Takahashi, Michihito, Shirai, Wataru, Fujiwara, Kosaku, Hayashi, Yuzo
• Format: Journal Article
• Language: English; Japanese
• Published: Tokyo JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY 1996; The Japanese Society of Toxicologic Pathology; Japan Science and Technology Agency
• Subjects: Hamster; Lung tumor; N-methyl-N-nitrosourethane; Pulmonary fibrosis
• ISSN: 0914-9198; 1881-915X; 1347-7404
• DOI: 10.1293/tox.9.315

The relationship of pulmonary fibrosis to development of lung tumors was investigated in Syrian golden hamsters treated with N-methyl-N-nitrosourethane (MNUR). Female animals in groups 1 and 2 received five subcutaneous (sc) injections of 0.6 and 0.2mg, respectively, of the carcinogen, whereas males in group 3 were given a single 0.3mg sc dose. After initiation the animals in each group were maintained, together with controls, without any further treatment for 26 weeks, and then examined for whether proliferative lesions in the lung are secondary to pulmonary inflammatory lesions induced by MNUR. Lung tumors were induced in all hamsters of group 1, but only 56% and 36%, respectively, were accompanied by inflammatory lesions and pulmonary fibrosis. Similar results were also obtained for tumors in group 2 and papillary hyperplasias in the female treated groups, many being observed without any involvement of fibrotic lesions. Glandular metaplasia was observed at high frequency in groups 1-3, but no evidence of a histogenetic link with development of lung tumors was found. A close relation between development of lung tumors and papillary hyperplasias was noted, however. The present study thus suggested that a considerable proportion of lung tumors induced in hamsters by MNUR are independent of toxicity-related changes and presumably due to direct DNA initiating action of the carcinogen.