Effects of lead on haem biosynthesis during erythroid differentiation in vitro

Murine erythroleukaemia cells (MELC) are erythroid precursor cells that undergo erythroid differentiation in the presence of the inducer hexamethylene bisacetamide (HMBA). The effects of lead on haem biosynthesis in MELC following HMBA-induced differentiation were studied. MELC were induced with HMBA in the presence of 20, 40 and 80 mum-lead acetate and cell density, haem content, incorporation of (14)C-labelled delta-aminolaevulinic acid (ALA) into haem, and the activities of the enzymes delta-aminolaevulinic acid dehydratase (ALA-D), uroporphyrinogen I synthetase (URO-S) and ferrochelatase (FERRO) were determined. MELC exposed to 80 mum-lead showed significant erythroid hypoplasia (40-50%) and a significant decrease (30-50%) in haem content at 2, 4 and 6 days after induction in comparison with the controls. Significant inhibition of ALA-D, the most sensitive index, was noted at 20 mum-lead, and at 80 mum-lead ALA-D activity was decreased by 60-80% in comparison with the controls. URO-S and FERRO showed significant decreases of 34% and 50%, respectively, at 80 mum-lead. A decrease of 50% in the incorporation of [(14)C]ALA into haem at 80 mum-lead indicated an impairment in haem synthesis. The results suggest that the impairment of haem formation by lead is coincident with the production of severe erythroid hypoplasia.