Cytosine arabinoside transport by human leukaemic cells.
The membrane transport of cytosine arabinoside (araC) has been studied in blasts freshly isolated from a variety of acute leukaemias. The major fraction of araC influx was facilitated and this fraction was 80-87% at l microM araC and 68-80% at 200 microM araC. Competitive kinetics were observed between araC and deoxycytidine for entry into leukaemic blasts and, moreover, araC influx was blocked by phloretin, a broad-spectrum inhibitor of facilitated transport systems. Kinetic analysis of facilitated araC influx gave KmS which varied over a 10-fold range between patients and which were positively correlated to the Vmax. Nucleoside influx Vmax also varied over an 80-fold range between individuals, although the mean araC transport was 4-fold greater in myeloblasts than in lymphoblasts. Larger transport of araC may explain the greater sensitivity of acute myeloid leukaemia to this drug.
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000097:blood*; D003841:Deoxycytidine / Q000097:blood; D006801:Humans; D007223:Infant; D007700:Kinetics; D007938:Leukemia / Q000097:blood*; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D010693:Phloretin / Q000494:pharmacology; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology
D003561:Cytarabine; D003841:Deoxycytidine; D013868:Thioinosine; C001789:4-nitrobenzylthioinosine; D010693:Phloretin