Persistence of cyclophosphamide-induced damage in bone marrow as indicated by sister chromatid exchange analysis

Various treatment protocols were used to investigate the time-dependent decrease in sister chromatid exchanges (SCEs) in bone marrow cells following treatment of C57Bl/6J X DBA/2J F1 (DB2F1) mice by i.p. injection of cyclophosphamide (15 mg/kg). The major factor in the time-related decrease in SCE-inducing lesions is the considerable cytotoxicity or selection of less highly damaged cells over successive cyclophosphamide post-treatment cycles. A constant rate of selection of 0.61 and 0.65%, respectively, was apparent over post-treatment cycles 1-2 and 2-3. In addition, second- and third-division SCE data produced by various protocols indicate persistence of a fraction of cyclophosphamide's SCE-inducing lesions for at least three post-treatment cycles. Comparison of the persistence of cyclophosphamide's SCE-inducing lesions with our previously reported data for diepoxybutane and ethyl carbamate reveals that the rate of repair of SCE-inducing lesions is inversely related to tumorigenic activities.