Mechanisms in cyclophosphamide induction of cytogenetic damage in human lymphocyte cultures

Low-dose cyclophosphamide treatment of human lymphocyte cultures in concentrations ranging from 0.001 to 0.00001 microgram/ml produced a statistically significant dose response in chromosome breakage and cell death. However, a dose as high as 0.2 micrograms/ml did not produce significant damage in comparably treated whole blood cultures. These results suggest that lymphocytes in culture have the ability to metabolize the nonmutagenic cyclophosphamide parent compound to its more mutagenic metabolite, but that such conversion may be prevented by binding of cyclophosphamide to red blood cells.