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Abstract

Abstract


Objective: Granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage-colony stimulating factor (GM-CSF) are frequently used in cancer patients to overcome the granulocytopenic effects of chemotherapy, and also to mobilize the stem cells. The mobilized stem cells are collected from the peripheral blood and used for transplantation following high doses of chemotherapy. However, the molecular mechanism by which these colony stimulating factors (CSFs) bring about proliferation of myeloid precursor cells is not clearly known. Dihydrofolate reductase (DHFR), which has an established role in DNA synthesis, could be a link between administration of CSF and stem cell proliferation. The purpose of this study was to investigate whether CSFs induce white cell proliferation by producing multiple forms of DHFR.
Methods: Twelve patients with non-haematological malignancies were treated with either G-CSF or GM-CSF to mobilize stem cells. Nine healthy subjects were treated with placebo as controls. Blood samples were obtained before and after stimulation with CSFs or placebo. White blood cells were separated and concentrations of both active DHFR and immunoreactive nonfunctional form of DHFR were determined in their cytoplasm using methotrexate-binding assay and enzyme-linked immunosorbent assay, respectively. Total leucocytes count (TLC) was also monitored before and after stimulation with CSFs or placebo.
Results: There was a significant (P