Cellular and molecular toxicology of lead. III. Effect of lead on heme synthesis

The effect of lead nitrate on the biosynthesis of heme and the cellular uptake of (59)Fe was studied in an established rat liver cell line (RLC-GAI) grown in serum-free medium. Heme synthesis was shown to be increased in lead-treated cells when determined by measuring the amount of (59)Fe incorporated into the heme fraction of cell homogenates; concomitant with increased (59)Fe incorporation into heme, cellular uptake of (59)Fe was also increased. By contrast, heme synthesis was inhibited by lead in a dose-dependent manner when determined by measuring the conversion of ((14)C) aminolevulinic acid into heme under identical experimental conditions. Cellular degradation of heme was not found to be significantly affected by lead. It is proposed that lead inhibited the biosynthesis of heme and that the increased incorporation of (59)Fe into the heme fraction of the lead-treated cells was the result of the increased uptake of (59)Fe and hence labeling of the heme molecules. Evidence is presented that suggests that only (59)Fe present in solution as a low-molecular-weight complex was accumulated in increased amounts by lead-treated cells.