The Use of Ferrokinetics in the Study of Experimental Anemia

Abstract

Erythropoietic cells in bone marrow are vulnerable to cytotoxic substances. There are three types of erythroid precursors: cells that can take up Fe but do not proliferate (reticulocytes), those that can take up Fe and proliferate (normoblasts and pronormoblasts), and those cells that do not take up Fe but can proliferate and differentiate into the erythroid cell line (ERC and stem cells). Each of these erythroid precursors requires a certain time before they emerge into the peripheral blood as mature red blood cells. By applying our understanding of ferrokinetics associated with erythropoiesis, it was possible to estimate a cytotoxic effect of chemicals on proliferating erythgroid precursors (pronormoblasts) in mice by measuring 24-hr 59Fe uptake in red blood cells 48 hr after treatment with chemicals. The effect of chemicals on pluripotent hemopoietic stem cells in mice was also estimated by measuring 24-hr 59Fe uptake 72 hr after treatment with chemicals. The validity of experimental schemes was tested using cytarabine, methotrexate, vinblastine, cyclophosphamide, and busulfan, which are known to act against specific cell types. Effects on pluripotent hemopoietic stem cells were tested with or without activation of stem cells in G0 into cell cycle. Applications of the 59Fe uptake method in the study of (1) benzene toxicity and (2) effect of pentobarbital on the toxic action of hydroxyurea and cytarabine are described. Proper application of the ferrokinetic characteristics of erythropoietic cells enables the establishment of a methodology which can be used to evaluate potential toxic effects of chemicals on erythroid precursor cells and pluripotent hemopoietic stem cells.