Abstract

Acute lead (Pb) toxicity in mice, produced by a single i.v. injection of Pb acetate, was associated with transient erythroid hypoplasia and impaired utilization of RBC 59Fe for heme synthesis. The mechanism of this Pb-induced erythroid hypoplasia was further investigated in posthypoxic plethoric mice. When Pb and erythropoietin (EP) were administered simultaneously, the resultant erythroid response was diminished relative to EP-treated controls. Twelve hours after the simultaneous EP and Pb injection, the number of early (pro) normoblasts was comparable to EP-treated controls. By 24 hr, there was a reduction of intermediate normoblasts followed by a decreased transition of these cells to late normoblasts. Excess nonheme iron was demonstrated by cytochemical technique in the cytoplasm of intermediate normoblasts in Pb-treated mice. Administration of Pb at intervals before and after EP resulted in a depressed reticulocyte response relative to EP-treated controls. The nadir of this response was observed when Pb was given 16 hr after EP. From these studies, we would suggest that the effects of Pb on erythropoiesis are best explained by the intramedullary death of intermediate normoblasts. A decrease in the conversion of early to intermediate forms, with subsequent intramedullary death of early normoblasts, may also contribute to the depression of the erythroid response. The mechanism for erythroid hypoplasia in some cases of human plumbism could be, in large measure, attributable to this process.

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