Comparison of sister-chromatid exchange frequencies in mouse T- and B-lymphocytes after exposure to 4-hydroxycyclophosphamide or phosphoramide mustard.
The present study was designed to investigate the genotoxicity of 4-hydroxycyclophosphamide (4-OHCP) and phosphoramide mustard (PAM), both reactive metabolites of cyclophosphamide (CP), for possible differences in SCE-inducing activity in mouse T- and B-lymphocytes. Mouse peripheral blood lymphocytes were isolated and stimulated to divide with either phytohemagglutinin (T-cell mitogen) or lipopolysaccharide (a polyclonal B-cell activator). Significant concentration-dependent increases in SCE frequencies were observed for both 4-OHCP and PAM with both mitogens, with 4-OHCP being almost twice as potent as PAM. There was no difference in SCE response between T- and B-lymphocytes after exposure to either PAM or 4-OHCP. These data do not support the idea that the difference in SCE response in T- and B-lymphocytes by CP in vivo is due to differential responses to either of the proposed putative metabolites of CP.
Kwanyuen
P
P
Environmental Health Research and Testing Inc., Research Triangle Park, NC 27709.
Erexson
G L
GL
Bryant
M F
MF
Kligerman
A D
AD
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000633:toxicity; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009152:Mutagenicity Tests; D010752:Phosphoramide Mustards / Q000633:toxicity*; D010835:Phytohemagglutinins / Q000494:pharmacology; D012854:Sister Chromatid Exchange; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
D008070:Lipopolysaccharides; D010752:Phosphoramide Mustards; D010835:Phytohemagglutinins; C030090:phosphoramide mustard; C012358:4-hydroxycyclophosphamide; D003520:Cyclophosphamide