Methemoglobin Formation in Human Blood by Cobalt

Although the erythropoietic effect of cobalt has been amply demonstrated in experimental animals (1-3), in normal human beings (4, 5), and in certain types of anemia (4, 6-8), the mechanism of this increased blood formation has not been elucidated. No evidence has been adduced that administration of cobalt causes a decrease in oxygen capacity (9) or alters the oxygen dissociation curve (10, 11) in the blood either of experimental animals or of human beings. It has been suggested, therefore, that cobalt interferes with the cellular oxidative processes of the marrow, or of some other hypothetical regulatory center for erythropoiesis, thus producing a histotoxic anoxia (4), leading in turn to increased erythropoietic activity. Some support for this hypothesis is offered by observations which show that cobalt induces the formation of reversible complexes of oxygen with histidine or cysteine (12, 13). Moreover, Barron and Barron (14) have shown that the addition of cobalt in vitro diminishes the oxygen consumption of suspensions of red cells derived from rabbits made polycythemic by the previous administration of cobalt. These authors and Davis (15) have also demonstrated that the development of cobalt-induced polycythemia is prevented by the simultaneous administration of ascorbic acid, a reducing agent known to be effective in directly reducing methemoglobin to hemoglobin (16). It seems possible, then, that cobalt may exert its histotoxic effect by blocking the enzymatic reducing systems of cells, thus interfering with the utilization of oxygen by the cells.