Dose-independence of early, cyclophosphamide-induced lung damage in mice

Administration of cyclophosphamide to mice resulted in lung damage which was assessed by measuring breathing rate and lung compliance. Above a threshold dose (approximately 50-100 mg/kg b.w.) the time of onset and severity of early, acute pulmonary dysfunction was dose-independent in the range 100-400 mg/kg. At doses up to 200 mg/kg lung damage was reversible but above this second threshold level, pulmonary fibrosis invariably developed. The severity of late damage (approximately day 40) was dose-related. These findings may help in the interpretation of clinical lung damage associated with cyclophosphamide therapy.