Teleka Stanley, Chijuwa Alexander, Senga Edward, Chisi John E
Department of Hematology, College of Medicine, University of Malawi.
Malawi Med J. 2011 Dec;23(4):118-21.
Cytosine arabinoside (Ara-C) is an S-phase specific cytotoxic drug used in the treatment of malignancies. It is converted to Cytosine Arabinoside triphosphate (Ara-CTP) in the cell. Cytosine Arabinoside triphosphate, reversibly displaces deoxy cytidine triphosphate from DNA polymerase for incorporation into DNA. This process leads to cell death.
To investigate the in vivo effects of Ara-C on the Granulocyte Macrophage Colony Forming Cells (GM-CFC) and High Proliferative Potential Colony Forming Cells (HPP-CFC) respectively in mice.
Ara-C (150mg/kg) was administered intraperitoneally (i.p) once to mice and bone marrow cells sampled on days 1, 3 and 6.
Ara-C reduced the numbers of both GM-CFC and HPP-CFC in the bone marrow. HPP-CFCs were initially more sensitive to Ara-C treatment than GM-CFCs. In the six days after treatment the effect on GM-CFC persisted, while there was a partial recovery in the number of HPP-CFCs.
It is possible that Ara-C disturbs the stem cells niche by damaging the stromal cells of the bone marrow microenvironment. This would result in derangement of HPP-CFC proliferation.
阿糖胞苷(Ara-C)是一种用于治疗恶性肿瘤的S期特异性细胞毒性药物。它在细胞内转化为阿糖胞苷三磷酸(Ara-CTP)。阿糖胞苷三磷酸可从DNA聚合酶上可逆地取代脱氧胞苷三磷酸,从而掺入DNA中。这一过程导致细胞死亡。
分别研究阿糖胞苷对小鼠粒-巨噬细胞集落形成细胞(GM-CFC)和高增殖潜能集落形成细胞(HPP-CFC)的体内作用。
给小鼠腹腔注射(i.p)一次阿糖胞苷(150mg/kg),并在第1、3和6天采集骨髓细胞。
阿糖胞苷减少了骨髓中GM-CFC和HPP-CFC的数量。HPP-CFC最初比GM-CFC对阿糖胞苷治疗更敏感。治疗后的六天内,对GM-CFC的影响持续存在,而HPP-CFC的数量有部分恢复。
阿糖胞苷可能通过损害骨髓微环境的基质细胞来扰乱干细胞龛。这将导致HPP-CFC增殖紊乱。