Cytosine arabinoside reduces the numbers of granulocyte macrophage colony forming cells (GM-CFC) and high proliferative potential colony forming cells (HPP-CFC) in vivo in mice.

BACKGROUND 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. OBJECTIVE 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. METHODOLOGY Ara-C (150mg/kg) was administered intraperitoneally (i.p) once to mice and bone marrow cells sampled on days 1, 3 and 6. RESULTS 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. CONCLUSION 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.