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.
Sargent
L M
LM
University of Wisconsin, State Laboratory of Hygiene, Madison 53706.
Roloff
B
B
Meisner
L F
LF
D001711:Biotransformation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000187:drug effects*; D003520:Cyclophosphamide / Q000009:adverse effects* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure
D003520:Cyclophosphamide