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.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D002104:Cadmium / Q000494:pharmacology; D002413:Cations, Divalent; D005260:Female; D007501:Iron / Q000494:pharmacology; D007700:Kinetics; D008345:Manganese / Q000494:pharmacology; D008670:Metals / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000201:enzymology*; D009532:Nickel / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology
D002413:Cations, Divalent; D008670:Metals; D002104:Cadmium; D008345:Manganese; D009532:Nickel; D007501:Iron; D001189:Aryl Hydrocarbon Hydroxylases; D015032:Zinc