小児期急性白血病の細胞回転に対するCytosine arabinosideおよびDaunomycinの影響

抄録

The therapeutic effect of cytosine arabinoside and daunomycin on leukemic blast cells in the bone marrow was evaluated. Changes in proliferative capacity were evaluated by serial measurements of the number of cells in mitosis and the per cent of cells in deoxy-ribonucleic acid (DNA) synthesis and ribonucleic acid (RNA) synthesis as indicated by ability to incorporate ³H-thymidine or ³H-uridine. Seven cases of acute myeloblastic leukemia of children were studied. These patients had recieved and were resistant to all other standard chemotherapeutic agents at this time.
Cytosine arabinoside was given by an intravenous injection in a dose of 100 mg/m². The in vivo H³-thymidine labeling index of leukemic blast cells decreased rapidly 4 hours after injection of cytosine arabinoside and recovered within 24 hours. This phenemenon indicated that cytosine arabinoside inhibited DNA synthesis and achieved partial synchronization of the cells.
Daunomycin was given by an intravenous injection in a dose of 1 mg/kg body weight. Four hours after completion of the injection, there were no remarkable changes in mitotic and ³H-thymidine labeling indexes. Twenty-four to 48 hours after injection both mitotic and labeling indexes had decreased markedly and recovered to the control level gradually within 72 to 96 hours. Mean grain count of labeled cells were unchanged. The in vivo ³H-thymidine labeling index of cells decreased or increased 4 hours after injection of daunomycin. The in vitro ³H-thymidine lebeling index of leukemic cells decreased rapidly 4 hours after incubation with daunomycin. These data indicated that daunomycin inhibited DNA synthesis more slowly than cytosine arabinoside. One explanation was that leukemic cells in G₁ (G₀) phase could incorporate daunomycin injected, which would persist in the cells and show inhibitory effect of DNA synthesis when those cells marched into S phase. Another was that inhibitory effect of daunomycin for the leukemic cells in G₁ (G₀) phase to enter S phase, probably through inhibition of RNA synthesis.