Lead-dithiocarbamate interaction. Effect on ALAD activity in isolated rat hepatocytes

Abstract

Dithiocarbamates are known to markedly increase tissue uptake of lead and potentiate toxic effects of lead in rats. Effects of the interaction between lead and diethyldithiocarbamate (DTC) on the enzyme delta-aminolevulinic acid dehydratase, ALAD, were studied in primary cultures of rat hepatocytes, incubated with lead acetate, PbAc, or lead-diethyldithiocarbamate complex, Pb(DTC)2, labeled with 203Pb. Incubation of cells with the lipophilic Pb(DTC)2 complex caused a more rapid and stronger inhibition of ALAD activity than did PbAc. The effects of ALAD activity could be related to the cellular uptake of lead. Thus, a much higher and more rapid cellular uptake of lead was found following incubation with Pb(DTC)2 than with PbAc. Pb(DTC)2 inhibited ALAD activity also in vitro when incubated with purified ALAD enzyme. It is suggested that the increased inhibition of ALAD activity by Pb(DTC)2 is owing to facilitated cellular transport of lead in the complexed form and that complexing lead with DTC could serve as a experimental model in order to obtain high cellular concentrations of lead.