The effect of zinc and pH on the behaviour of delta-aminolevulinic acid dehydratase activity in baboons exposed to lead.

Four adult male baboons (Papio ursinus) were exposed to a cloud of lead oxide dust to induce changes in the status of delta-aminolevulinic acid dehydratase (ALAD). Enzyme activity fell rapidly to a steady state as blood lead levels rose above normal. Exogenous zinc was shown to activate the enzyme, and the antagonistic effect of zinc on in vivo and in vitro lead inhibition was demonstrated for baboons. In baboons not exposed to lead dust, ALAD showed an activity optimum at pH 7-1 which shifted to pH 6-8 with in vitro addition of lead. In baboons exposed to lead dust, with raised blood lead, activity optima were observed at pH 6-8 and 6-2, while the optimum at pH 7-1 was absent.

The effect of vinyl chloride monomer, chloroethylene oxide and chloracetaldehyde on DNA synthesis in regenerating rat liver.

Vinyl chloride monomer used in the manufacture of polyvinyl chloride is a chemical of increasing industrial importance but has recently been incriminated as a carcinogen, producing a mutagenic effect after being metabolized to active metabolites. The initial effect of vinyl chloride monomer and two of its presumed metabolites, chloracetaldehyde and chloroethylene oxide, on DNA synthesis was investigated in vivo in regenerating rat liver. The established control curve for the DNA synthesis rate after partial hepatectomy demonstrated two waves of synthetic activity at 21 and 30 h. Vinyl chloride, injected intravenously immediately on completion of the operation, depressed the first wave of DNA synthesis by 49.6%. The second peak of DNA synthetic activity was similar to that of the control. Chloracetaldehyde and chloroethylene oxide both produced similar effects on the first wave of DNA synthesis after partial hepatectomy, inhibiting the DNA synthesis rate by approx. 50%. After a regenerating period of 27 h, however, they produced very different effects, chloroethylene oxide raising the control DNA synthesis rate at 30 h by 49% while chloracetaldehyde tended to desynchronize the well-defined second peak of the control. The test compounds have been compared to literature reports of the inhibitory effects of various carcinogens on DNA synthesis.

The in vitro effect of zinc on the inhibition of human delta-aminolevulinic acid dehydratase by lead.

The antagonistic effect of zinc on inhibibition of human aminolevulinic acid dehydratase (ALAD) by lead was examined in vitro. The phenomenon was studied at pH 6.5-7.5 . Zinc and lead were added at concentrations ranging from physiological levels to levels far in excess of those expected in heavy industrial exposure. ALAD activity of normal blood assayed in the presence of zinc was unaffected by exogenous lead if the added zinc concentration was above 0.53 mmol/l blood, or double the normal endogenous level, and was of the order found in heavy industrial exposure to zinc. In this case, ALAD assay values were appreciably raised and might have fallen into the normal range in spite of a dangerous total blood lead of over 0.0048 mmol/l. When zinc was added in vitro to blood from a worker with a blood lead level of 0.0043 mmol/l the ALAD values obtained were also raised and did not reflect the dangerous level of lead in the patient.