Abstract
Lesions were induced in the lungs of specific-pathogen-free F344 rats by chronic tobacco smoke exposure. Animals exposed to 7 cigarettes/day were killed after 1, 1.5, or 2 years of exposure. Parallel lifetime exposures induced pulmonary tumors in 9% of the animals. In serially killed animals, four types of lesions were found: 1) perivascular or peribronchiolar accumulation of lymphoreticular cells, 2) fibrotic and cellular enlargement of peribronchiolar septa, 3) type II cell hyperplasia with septal fibrosis, and 4) air-space enlargement (emphysema). However, emphysema occurred only in animals exposed to a higher (10 cigarettes) dose of tobacco smoke. Ultrastructural studies showed all of the focal lesions to be infiltrated by cells typical of the inflammatory response. The type II hyperplastic and peribronchiolar alveolar lesions involved larger portions of the parenchyma in fibrotic changes but differed in structure, location, and frequency. The incidence of the peribronchiolar alveolar lesions was temporally related to tumor incidence.
Footnotes
Supported by the Environmental Protection Agency under interagency agreement 81-D-X0533; by the National Cancer Institute under interagency agreement 40-484-74; and by the Office of Health and Environmental Research, U.S. Department of Energy, under contract W-7405-eng-26 with the Union Carbide Corporation.
Animals were maintained under the guidelines set forth by the Biology Division, Oak Ridge National Laboratory.
We are grateful to Dr. Paul Nettesheim, National Institute of Environmental Health Sciences, Durham, N.C.: to Dr. Michael Fry and Dr. Robert Ullrich, Oak Ridge National Laboratory, Oak Ridge, Tenn., for support and critical comments on the manuscript; and to Dr. Donald Swartzendruber, Oak Ridge Associated Universities, Oak Ridge, Tenn., for the use of his electron microscope facility. We thank Mr C. D. Farmer for technical assistance.