||Comparison of Sister-Chromatid Exchange in Mouse Peripheral Blood Lymphocytes Exposed In vitro and In vivo to Phosphoramide Mustard and 4-Hydroxycyclophosphamide.
Bryant, M. F. ;
Erexson, G. L. ;
Kligerman, A. D. ;
||Health Effects Research Lab., Research Triangle Park, NC. Genetic Toxicology Div. ;Environmental Health Research and Testing, Inc., Research Triangle Park, NC. ;Cornell Univ., Ithaca, NY.
In vitro ;
In vivo ;
Sister chromatid exchange ;
Phosphoramide mustards ;
Dose-response relationships ;
Cell cycle ;
Antitumor drug screening assays ;
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Cyclophosphamide (CO) and two of its known metabolites, 4-hydroxycyclophosphamide (4-OHCP) and phosphoramide mustard (PAM), were analyzed for their ability to induce sister chromatid exchanges (SCEs) in mouse peripheral blood lymphocytes (PBLs) in vitro and in vivo. It is concluded that at equimolar concentrations, CP is a more potent SCE inducer in vivo than PAM and that PAM and 4-OHCP induce equal numbers of SCEs in a dose-dependent manner. The present study also shows that these metabolites of CP are more potent SCE inducers than CP itself in vitro. This relationship might be explained by the differences in pharmacokinetics of these compounds. (Copyright (c) 1989 Elsevier Science Publishers. B.V. (Biomedical Division).)