asta-z-7557 and phosphoramide-mustard

asta-z-7557 has been researched along with phosphoramide-mustard* in 1 studies

Other Studies

1 other study(ies) available for asta-z-7557 and phosphoramide-mustard

ArticleYear
Aldehyde dehydrogenase activity as the basis for the relative insensitivity of murine pluripotent hematopoietic stem cells to oxazaphosphorines.
    Biochemical pharmacology, 1985, Oct-01, Volume: 34, Issue:19

    The ex vivo sensitivity of murine pluripotent hematopoietic stem cells (CFU-S) and myeloid progenitor cells (CFU-GM) to 4-hydroperoxycyclophosphamide, ASTA Z 7557, phosphoramide mustard, acrolein, melphalan, and cis-platinum was determined in the absence and presence of known (disulfiram, diethyldithiocarbamate, cyanamide) or suspected [ethylphenyl(2-formylethyl)phosphinate] inhibitors of aldehyde dehydrogenase activity. As compared to CFU-GM, CFU-S were less sensitive to the oxazaphosphorine agents, 4-hydroperoxycyclophosphamide and ASTA Z 7557. The two cell populations were approximately equisensitive to acrolein as well as to the non-oxazaphosphorine cross-linking agents, phosphoramide mustard, melphalan and cis-platinum. All four inhibitors of aldehyde dehydrogenase activity potentiated the cytotoxic action of the oxazaphosphorines toward CFU-S; they did not potentiate the cytotoxic action of acrolein or the non-oxazaphosphorines toward these cells. The inhibitors did not potentiate the cytotoxic action of the oxazaphosphorines, non-oxazaphosphorines, or acrolein toward CFU-GM. Pyridoxal, a substrate for aldehyde oxidase, did not potentiate the cytotoxic action of oxazaphosphorines toward CFU-S. Cellular NAD-linked aldehyde dehydrogenases are known to catalyze the oxidation of the major transport form of cyclophosphamide, 4-hydroxycyclophosphamide/aldophosphamide, to an inactive metabolite, carboxyphosphamide. Our observations suggest that (1) aldehyde dehydrogenase activity is an important determinant of the sensitivity of a cell population to the oxazaphosphorines, (2) CFU-GM lack the relevant aldehyde dehydrogenase activity, and (3) the phenotypic basis for the relative insensitivity of CFU-S to oxazaphosphorines is the aldehyde dehydrogenase activity contained by these cells.

    Topics: Acrolein; Aldehyde Dehydrogenase; Animals; Bone Marrow Cells; Cisplatin; Colony-Forming Units Assay; Cyanamide; Cyclophosphamide; Disulfiram; Ditiocarb; Drug Synergism; Granulocytes; Hematopoietic Stem Cells; Male; Melphalan; Mice; Mice, Inbred BALB C; Nitrogen Mustard Compounds; Organophosphorus Compounds; Phosphinic Acids; Phosphoramide Mustards

1985