A comparison of the lethal effects in culture of cytosine arabinoside and arabinofuranosyl-5-azacytosine acting on the blast cells fo acute myeloblastic leukemia.
Two culture methods are available for the study of the blast cells of acute myeloblastic leukemia (AML); first, a minority of blast cells will form colonies in methylcellulose cultures in the presence of suitable growth factors. Second, clonogenic blast cells will increase in suspension cultures. Both methods can be used to assess the sensitivity of blasts to chemotherapeutic drugs, but different dose-response curves are obtained with each. Thus cytosine arabinoside (ara-C) is more toxic to clonogenic blasts in suspension than in methylcellulose, while for 5-azacytidine (5-aza) the reverse is seen. Arabinofuranosyl-5-Azacytosine (ara-AC) combines the chemical features of the two drugs. That is, its sugar moiety has the same diastereomeric change in the furanose ring as ara-C and its pyrimidine ring has the same substitution of nitrogen for carbon at the 5' position as 5-aza. We compared the sensitivity of AML blasts with ara-Ac in suspension and in methylcellulose. As a control, the same comparison was made for the sensitivities to ara-C. Blast cells were less sensitive to ara-AC than to ara-C under all conditions; but, ara-AC sensitivity was greater for cells in methylcellulose than for cells in suspension. Thus, AML blasts respond to ara-AC in culture with a pattern similar to that of 5-aza and opposite to that of ara-C. Since ara-C is a more useful drug in the treatment of AML than 5-aza, we interpret the culture results as predicting that ara-AC may not be effective in AML.
Yang
G S
GS
Ontario Cancer Institute, Toronto, Canada.
McCulloch
E A
EA
D000208:Acute Disease; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001374:Azacitidine / Q000627:therapeutic use* / Q000031:analogs & derivatives; D001752:Blast Crisis / Q000188:drug therapy* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000627:therapeutic use*; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D003561:Cytarabine; C022121:fazarabine; D001374:Azacitidine