Inhibition of hemoglobin production by transferrin-gallium. Blood 1987 Jan;69(1):144-9
Date
01/01/1987Pubmed ID
3790721Scopus ID
2-s2.0-0023103598 (requires institutional sign-in at Scopus site) 36 CitationsAbstract
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.
Author List
Chitambar CR, Zivkovic ZMESH terms used to index this publication - Major topics in bold
Anemia, HypochromicAnimals
Cell Division
Cell Line
Cytarabine
Dimethyl Sulfoxide
Erythropoiesis
Gallium
Hemoglobins
Iron
Isoniazid
Mice
Pyridoxal
Receptors, Transferrin
Transferrin
