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CR Chitambar and Z Zivkovic
Recent clinical trials evaluating gallium nitrate as a chemotherapeutic
agent have reported the development of microcytic hypochromic anemia in
patients treated with this agent. Because gallium is known to bind avidly
to transferrin, we examined the effect of transferrin-gallium (Tf-Ga) on
hemoglobin production by Friend erythroleukemia cells in vitro. Cellular
hemoglobin production, as assessed by benzidine staining, cellular
hemoglobin content, and 59Fe incorporation into heme, was significantly
decreased following exposure of cells to Tf-Ga. Tf-Ga led to an early
decrease in cellular 59Fe incorporation even before changes in hemoglobin
production were detected. A marked increase in cellular transferrin
receptor expression occurred following exposure of cells to Tf-Ga. Tf-Ga
inhibition of hemoglobin production could be reversed and hemoglobin
production could be restored to normal by addition to the media of either
transferrin-iron (Tf-Fe) or iron- pyridoxal isonicotinoyl hydrazone, a
compound capable of supplying iron directly to reticulocytes for heme
synthesis without transferrin as a mediator. These studies provide an
explanation for the development of anemia in patients treated with gallium
nitrate and suggest that gallium's mechanism of chemotherapeutic action
includes inhibition of cellular iron incorporation.
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| Copyright © 1987 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||