Aryl hydrocarbon receptor (AhR)-mediated induction of xanthine oxidase/xanthine dehydrogenase activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an environmental contaminant, i nduced xanthine oxidase and xanthine dehydrogenase (XO/XDH) activities, in addition to ethoxyresorufin-O-dealkylase and methoxy-resorufin-O-dealkylase activities in liver of mice. When TCDD was given to mice as a single oral dose of 40 mug/kg, the activities of XO and XDH increased about threefold w ithin 3 days and the increased levels were maintained for 4 weeks. The trea tment of mice with 5-methyl-cholanthrene also induced XO/XDH activities, bu t phenobarbital and dexamethasone had no effect. The level of aldehyde oxid ase, a molybdenum flavoenzyme related to XO/XDH, in mouse liver was also en hanced about 1.5-fold by TCDD treatment. The inducing effect of TCDD and 3- methylcholanthrene was not observed in null mice (AhR(-/-)), which lack the AhR gene. XO and XDH activities were induced by TCDD in heterozygous mice (AhR(+/-)). The lipid peroxidation in liver was stimulated by TCDD. The ind uction of XO and XDH, which produces reactive oxygen species, may contribut e to the various toxicities of TCDD. (C) 2001 Academic Press.