In vitro effect of captopril and three captopril metabolites on neutrophilic progenitor cells from normal mice and mice given busulfan.
Neutrophilic progenitor cells (CFU-NM) in mice with busulfan-induced latent bone marrow hypoplasia have been shown to be selectively suppressed by captopril in vivo. To study this further, marrow from mice given busulfan was used to test for myelotoxicity in vitro. It was found that myelotoxic agents, such as doxorubicin, cytarabine, 1,3-bis(2-chloroethyl)-1-nitrosourea, and chloramphenicol have the same suppressive effect in vitro on CFU-NM obtained from normal marrow as obtained from marrow of mice given busulfan. Our results suggest that in vitro, the CFU-NMs from mice given busulfan are not excessively sensitive to the action of at least these myelotoxic agents. It was also found that neither captopril nor three known captopril metabolites suppress CFU-NM from mice given busulfan. This result suggests either that the myelotoxicity induced in vivo by captopril is not caused by the parent compound or any of the three metabolites tested, or more likely, that the suppressive action of captopril on CFU-NM in vivo is caused by the suppression of an earlier myeloid progenitor cell.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002066:Busulfan / Q000494:pharmacology*; D002216:Captopril / Q000378:metabolism / Q000494:pharmacology*; D002701:Chloramphenicol / Q000494:pharmacology; D003114:Colony-Forming Units Assay; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D066298:In Vitro Techniques; D051379:Mice; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D011392:Proline / Q000031:analogs & derivatives*
D000970:Antineoplastic Agents; D002701:Chloramphenicol; D011392:Proline; D002216:Captopril; D002066:Busulfan