In vitro effect of lead acetate on human erythropoietic progenitors

Lead is known to induce hematological disturbances resulting from abnormali ties in cell differentiation and hemoglobin synthesis during hematopoiesis. The aim of the present work was to study human erythropoiesis in vitro in the presence of lead. Human erythroblastic progenitors, burst-forming units -erythroid (BFU-E), were exposed to lead acetate at increasing concentratio ns during 14 days of culture. Hematotoxicity was evaluated in vitro accordi ng to proliferation and differentiation of cell colonies arising from BFU-E development. The ability of cells to synthesize proteins, porphyrins, and hemoglobin was measured by spectrophotometric tests and by high-pressure li quid chromatography (HPLC). Results showed that in the presence of 10(-3) m ol/L lead acetate, no hemoglobinized cells were observed in culture and no fluorescent porphyrins were detected in cells. Up to 10(-3) mol/L, lead ace tate is not cytotoxic, i.e., it does not induce cell destruction. The prese nt work demonstrates that lead acetate interferes with the porphyrin synthe sis of human erythroblastic progenitors in vitro. The decrease of porphyrin content with 10(-5) mol/L lead acetate suggest that delta -aminolevulinic acid dehydratase can be inhibited by lead acetate during in vitro erythropo iesis. In vivo erythropoiesis occurs in the bone marrow. As about 95% of th e body burden of lead in adults is located in the bones with a biological h alf-life of some years, the concentration of lead acetate found to block po rphyrin synthesis in vitro has to be compared with in situ bone marrow lead concentrations.