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 degrees 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.