Quantitation of resistance of leukemic cells to cytosine arabinoside from BrdUrd/DNA bivariate histograms.
The cytotoxicity of ara-C derives from an inhibition of DNA synthesis after incorporation of ara-CTP into DNA. The rate of DNA synthesis can be determined from the amount of bromodeoxy-uridine (BrdUrd) incorporated into cells after a short exposure to BrdUrd. We developed a computer program to quantify the inhibition of the rate of DNA synthesis by analysis of the distribution of BrdUrd/DNA. Inhibition was evaluated in ara-C-sensitive and resistant cells after incubation with different doses of ara-C. An index of resistance to ara-C (RI) was expressed as the ratio of the amount of BrdUrd incorporated into S phase cells incubated with ara-C to that incorporated in the absence of ara-C. In the ara-C-sensitive and resistant HL60 cells, a linear relationship between RI and log ara-C concentration was observed. Small numbers of slightly resistant cells in mixtures of ara-C-sensitive and resistant cells could be determined using this method, making it suitable for clinical use to test the resistance of leukemic cells to ara-C.
Lacombe
F
F
Laboratoire d'Hématologie, CHR Bordeaux, Hôpital Haut-Lévêque, Pessac, France.
Belloc
F
F
Dumain
P
P
Puntous
M
M
Lopez
F
F
Bernard
P
P
Boisseau
M R
MR
Reiffers
J
J
D001973:Bromodeoxyuridine; D003561:Cytarabine / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis*; D004351:Drug Resistance; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D008297:Male; D012984:Software; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004273:DNA, Neoplasm; D003561:Cytarabine; D001973:Bromodeoxyuridine