An evaluation of the tumorigenicity of cyclophosphamide and urethan in newborn mice.

Abstract The tumorigenic potential of cyclophosphamide was compared with that of the known tumorigen urethan by ip administration of normal saline or 0.8, 4.0 or 20.0 mg/kg of cyclophosphamide or 700.0 mg/kg of urethan to newborn offspring of Charles River CD ® -1 strain mice within 24 hr of birth and at 3 and 6 days of age. Tissues and organs from mice dying during the study or sacrificed at 79 weeks were examined grossly and microscopically. Cyclophosphamide was not leukemogenic. The incidence of malignant lymphoma was comparable for the control, low- and middle-dose groups and histologic evidence of this neoplastic disease was totally absent from the high-dose cyclophosphamide-treated mice. Liver neoplasms did not occur in the low- and high-dose cyclophosphamide groups, and the frequencies in the middle-dose group and the controls were similar. The frequency of pulmonary adenoma development was slightly increased in the low- and middle-dose cyclophosphamide-treated males and females and high-dose cyclophosphamide-treated females but neoplastic and hyperplastic lesions were totally absent from the lungs of the high-dose cyclophosphamide-treated males. Urethan was leukemogenic as malignant lymphomas developed in a high percentage of the urethan-treated male and female mice. The urethan-treated males also had an increased incidence of neoplasms and hyperplastic nodules in the lungs and liver.