Pulmonary Toxicity of Cytostatic Drugs: Cell Kinetics

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 withthree cytostatic drugs: cyclophosphamide, busulfan, or l,3-bis(2-chloroethyl)-l-nitro-sourea(BCNU). The alveolar labeling index was measured following drugadministration with a pulse of ³H-labeled thymidine and autoradiography.In cyclophosphamide-treated animals, peak alveolar cell proliferationwas seen 5 days after injection of the drug. In animals treatedwith busulfan or BCNU, proliferation was even more delayed (occurring2–3 weeks after administration). In contrast, with oleicacid, the highest alveolar cell labeling was found 2 days afterintravenous administration. In animals exposed to a cytostaticdrug, proliferation of type II alveolar cells was never a prominentfeature whereas in animals treated with oleic acid there wasan initial burst of type II cell proliferation. It is concludedthat the patterns of pulmonary repair vary between chemicalsdesigned to interfere with DNA replication as compared to agentswhich produce acute lung damage such as oleic acid.