Effects of cadmium on in vitro and in vivo erythropoiesis: erythroid progenitor cells (CFU-E), iron, and erythropoietin in cadmium-induced iron deficiency anemia.

Effects of cadmium (Cd) on in vitro and in vivo erythropoiesis in rats were studied by methylcellulose colony assay. Cd suppressed the in vitro growth of late erythroid progenitors (CFU-E) in a dose-dependent fashion and did not lose its inhibitory potency with increasing doses of erythropoietin (EPO). In addition, in marrow suspension cultures, Cd did not significantly influence 59Fe incorporation into both the cells and heme, and the Cd dose-responsive inhibition curve of the number of living cells was similar to that of CFU-E. These results suggest that the suppression of CFU-E colony formation by Cd is not due to the blocking of either EPO action to stimulate the growth of CFU-E or the iron incorporation into the cells ahd heme, but due to its direct cytotoxic effect. The colony suppression by Cd could be prevented by adding metallothionein to the cultures. On the other hand, oral administration of Cd to animals (100 mg/liter in drinking water) induced an iron deficiency anemia characterized by microcytic hypochromic red cells, decreased plasma iron, and increased total iron binding capacity. Marrow CFU-E density steadily increased as plasma iron decreased due to Cd administration and reached a plateau after 50 days. Plasma EPO titers were also found to be elevated in such a Cd-induced anemia. Parenteral iron administration during the Cd drinking period could completely prevent the development of iron deficiency anemia and the increase of both CFU-E and plasma EPO. There was a hyperbolic correlation between CFU-E and plasma iron or transferrin saturation. These results demonstrate that oral CD administration produces bone marrow hyperplasia at the CFU-E level due to iron deficiency.