Increased accumulation of cytosine arabinoside in human leukemic cells and enhancement of its cell-killing activity by uridine.
The effects of uridine(UR) on the cell-killing activity of cytosine arabinoside(ara-C) against human leukemic cells, MOLT-4, and on ara-C accumulation in cells were studied. The 50% lethal dose(LD50) of ara-C as determined by clonogenic assay was decreased to 5.0 x 10(-8) mol from 9.0 x 10(-7) mol after 3 days exposure to 10(-3) mol of UR. The accumulation of 3H-ara-C at 24 and 48 h was significantly increased in culture medium containing 10(-8) mol of 3H-ara-C and 10(-3) mol of UR (5,129 +/- 123.5 vs 2,554 +/- 115.5 cpm/10(5) cells at 24 h, p less than 0.01, and 5,772 +/- 123.2 vs 1,372 +/- 51.8 cpm/10(5) cells at 48 h, p less than 0.01). It is noteworthy that cell-killing activity of ara-C against human leukemic cells was enhanced by the combination with a nucleoside(UR), but not with antileukemic agents.
Takahashi
I
I
Department of Medicine, Kochi Municipal Central Hospital, Japan.
Hayashi
N
N
Nakamura
T
T
Matuzaki
T
T
Murase
T
T
Osada
K
K
Takeuchi
M
M
Ueki
Y
Y
Nakada
H
H
Yorimitsu
S
S
D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000378:metabolism* / Q000494:pharmacology; D004357:Drug Synergism; D006801:Humans; D007938:Leukemia / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D014407:Tumor Cells, Cultured; D014529:Uridine / Q000494:pharmacology*
D003561:Cytarabine; D014529:Uridine