Mechanism of arsenic-induced inhibition of erythropoiesis in mice.
Anemia accompanies arsenic intoxication in man. The present studies were undertaken to clarify further the effects of arsenic on erythropoiesis. A dose-related inhibition of red cell 59 Fe incorporation and reticulocyte response was observed in normal mice treated with a single injection of arsenic. Arsenite was approximately two times as inhibitory as arsenate. The effects of arsenic on erythropoietin-induced erythroid differentation revealed a significant inhibitory effect on young, proliferating marrow nucleated erythroid precursor cells. More mature, nonproliferating nucleated erythr oid cells were resistant to the toxic action of arsenic. A dose-related inhibitory effect of arsenic on DNA synthesis was observed in fetal liver nucleated erythroid cells incubated with 3 H thymidine. Ineffective erythropoiesis as well as the megaloblastic morphology accompanying aberrant DNA synthesis -- manifestations of arsenic toxicity in man -- were not evident in the present studies.
D000818:Animals; D001151:Arsenic / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism*; D004920:Erythropoiesis / Q000187:drug effects*; D005260:Female; D007501:Iron / Q000378:metabolism*; D051379:Mice
D004247:DNA; D007501:Iron; D001151:Arsenic