Increased Deoxycytidine Kinase mRNA Level After Treatment with Interleukin-3.

Abstract

Pretreatment of IL-3 to Kasumi-1 human acute myeloid leukemia cells enhanced 1-B-D-arabinofuranosyl cytosine (ara-C) cytotoxicity 1.2. to 1.4-fold (median 1.3). To clarify the mechanism of interleukin-3 (IL-3) on ara-C cytotoxicity, we investigated the level of deoxycytidine kinase mRNA with the competitive polymerase chain reaction method and enzyme activities, the incorporation of [(3)H] ara-C into DNA and intracellular ara-cytidine triphosphate (CTP) levels with high-performance liquid chromatography and analyzed cell cycles. The level of deoxycytidine kinase mRNA showed a fourfold increase (88.3 plus minus 4.33 amol &mgr;g of total RNA) at 3 days after treatment with IL-3 compared to control (20.3 plus minus 4.33 amol &mgr;g). After IL-3 treatment, ara-C incorporation into the DNA was increased to 1.33 to 1.83-fold (median, 1.73-fold). The G0/G1 late-phase and S-phase percentages of cells were increased from 28.99 to 78.73% in the IL-3 treatment group as compared to control. These results indicate that IL-3 pretreatment increases the level of deoxycytidine kinase mRNA and ara-C incorporation into the DNA and also increases ratios of G0/G1 late-phase and S-phase subsequent to an enhancement of ara-C cytotoxicity against leukemia cells.