In Vitro Inhibition of Aryl Hydrocarbon Hydroxylase by Heavy Metals

Inhibition of mouse hepatic aryl hydrocarbon hydroxylases (AHH), microsomal mixed-function oxidases was obtained with five bivalent metal chlorides. Concentrations ranged from 10––6 to 10––1 m. The enzyme system was induced by an intraperitoneal injection of a trioctanoin solution of 3-methylcholanthrene into C57B1/6J mice 24 hours before the hepatic AHH was measured. Activity was calculated as: ng of 3-hydroxybenzo(a)pyrene formed in 20 min at 37°C per mg of protein. Cadmium was the most inhibitory of the metals tested. Zinc inhibited the enzyme system more than iron, manganese, or nickel. At 10––4 m, ferrous ion slightly stimulated the activity, but at 10––5 and 10––3 m, it was inhibitory. Manganese failed to stimulate the enzyme activity as reported by others.