Arsenite exposure inhibits the erythroid differentiation of human hematopoietic progenitor CD34+ cells and causes decreased levels of hemoglobin

Abstract

Arsenic exposure poses numerous threats to human health. Our previous work in mice has shown that arsenic causes anemia by inhibiting erythropoiesis. However, the impacts of arsenic exposure on human erythropoiesis remain largely unclear. We report here that low-dose arsenic exposure inhibits the erythroid differentiation of human hematopoietic progenitor cells (HPCs). The impacts of arsenic (in the form of arsenite; As3+) on red blood cell (RBC) development was evaluated using a long-term culture of normal human bone marrow CD34+-HPCs stimulated in vitro to undergo erythropoiesis. Over the time course studied, we analyzed the expression of the cell surface antigens CD34, CD71 and CD235a, which are markers commonly used to monitor the progression of HPCs through the stages of erythropoiesis. Simultaneously, we measured hemoglobin content, which is an important criterion used clinically for diagnosing anemia. As compared to control, low-dose As3+ exposure (100 nM and 500 nM) inhibited the expansion of CD34+-HPCs over the time course investigated; decreased the number of committed erythroid progenitors (BFU-E and CFU-E) and erythroblast differentiation in the subsequent stages; and caused a reduction of hemoglobin content. These findings demonstrate that low-dose arsenic exposure impairs human erythropoiesis, likely by combined effects on various stages of RBC formation.

Arsenite Methyltransferase Is an Important Mediator of Hematotoxicity Induced by Arsenic in Drinking Water

“…The findings from our group have established that exposure to environmentally relevant levels of As III results in the development of anemia via the suppression of erythropoiesis in the bone marrow [14,[30][31][32][33][34]. In the present study, we found that the As3mt genotype has a critical role in mediating the hematotoxicity of arsenic.…”

“…However, the extent that As III directly mediates the suppression of erythropoiesis in vivo remains unknown. In the present study, we evaluated the contribution of the As3MT-dependent biotransformation to the arsenic-induced hematotoxicity identified in our previous experiments [14,[30][31][32][33][34]. This study provides novel information regarding the relative contribution of inorganic As III vs. methylated metabolites to the development of As III -induced anemia.…”