Role for Aldehyde Dehydrogenase in Survival of Progenitors for Murine Blast Cell oDhosDhamide in Vitro' Colonies after Treatment with 4-Hydroperoxycy
We have studied the effects of 4-hydroperoxycyclophosphamide (4- HC)on murine hemopoietlc progenitors. We found dose-dependent killing and differential sensItivItIes of colony forming cells with burst forming units-erythrocyte being most sensitive and colony-forming units-granu locyte/erythrocyte/macrophage/megakaryocytemost resistant. We also tested the effects of 4-HC on more primitive murine progenitors which wereIdentIfIable in our assaysystemwhenthe addItiOnof interleukin-3 was delayed until Day 7. We found that the senslth'itiesofthe progenitors for blast cell coloniesare similar to thoseof colony-formingunits that late-np pairing blast cell colonies were particularly resistant to 4-HC. mechanismof sensitivities of sensitIvItIesof murine afterbriefinCUbatiOnwithdiethylaminobenzaldehyde,aninhib itor ofaldehyde dehydrogenase. Progenitors for granuincyte/amcrophage colonies, granulocyte/erythrocyte/macrophage/megakaryocyte differential sensitivItIesof progenitorsdisappearedfollowing We also tested the sensitIvities ofthe progenitors to phenylketophosphainide, an analogue of 4-HC which is resistant to inactivation by aldehyde dehydrogenase. Various colony-forming units exhibited a similar dose response to this compound. These data indicate that intracellular levels of aldehyde dehydrogenase might play an Important role in differential sensitivities of murine