Cellular and molecular toxicology of lead. II. Effect of lead on delta-aminolevulinic acid synthetase of cultured cells.

The effect of lead nitrate on delta-aminolevulinic acid synthetase (ALA synthetase), the first and rate-limiting enzyme of the heme biosynthetic pathway, was studied by using an established rat liver cell line (RLC-GAI). Lead was shown to produce a time-dependent increase in ALA synthetase activity, with a maximum after incubation of the cells for 24 h with 10(-5) M lead nitrate. The effect of lead was not liver-specific in that increases in enzyme activity were produced in other tissue-derived cell lines. Cycloheximide but not actinomycin D, cordycepin, or hydroxyurea, at concentrations that inhibit the synthesis of protein, RNA, and DNA, prevented the lead-associated increase in ALA synthetase activity. Heme, added to the cells as hemin, also prevented the effect of lead. These results indicate that lead induced the synthesis of ALA synthetase secondary to an inhibition of the synthesis of heme.