© 1987 Oxford University Press
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Pulmonary Toxicity of Cytostatic Drugs: Cell Kinetics1
Biology Division, Oak Ridge National Laboratory Oak Ridge, Tennessee 37831 *Engineering Physics and Math Division, Oak Ridge National Laboratory Oak Ridge, Tennessee 37831
Pulmonary Toxicity of Cytostatic Drugs: Cell Kinetics. WITSCHI, H., GODFREY, G., FROME, E., and LINDENSCHMIDT, R. C. (1987). Fundam. Appl. Toxicol. 8, 253–262. Mice were treated with three cytostatic drugs: cyclophosphamide, busulfan, or l,3-bis(2-chloroethyl)-l-nitro-sourea (BCNU). The alveolar labeling index was measured following drug administration with a pulse of 3H-labeled thymidine and autoradiography. In cyclophosphamide-treated animals, peak alveolar cell proliferation was seen 5 days after injection of the drug. In animals treated with busulfan or BCNU, proliferation was even more delayed (occurring 2–3 weeks after administration). In contrast, with oleic acid, the highest alveolar cell labeling was found 2 days after intravenous administration. In animals exposed to a cytostatic drug, proliferation of type II alveolar cells was never a prominent feature whereas in animals treated with oleic acid there was an initial burst of type II cell proliferation. It is concluded that the patterns of pulmonary repair vary between chemicals designed to interfere with DNA replication as compared to agents which produce acute lung damage such as oleic acid.