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, induced xanthine oxidase and xanthine dehydrogenase (XO/XDH) activities, in addition to ethoxyresorufin-O-dealkylase and methoxyresorufin-O-dealkylase activities in liver of mice. When TCDD was given to mice as a single oral dose of 40 microg/kg, the activities of XO and XDH increased about threefold within 3 days and the increased levels were maintained for 4 weeks. The treatment of mice with 3-methylcholanthrene also induced XO/XDH activities, but phenobarbital and dexamethasone had no effect. The level of aldehyde oxidase, a molybdenum flavoenzyme related to XO/XDH, in mouse liver was also enhanced 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 induction of XO and XDH, which produces reactive oxygen species, may contribute to the various toxicities of TCDD.
Institute of Pharmaceutical Science, Department of Anatomy, Hiroshima University School of Medicine, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan.
K
K
Sugihara
S
S
Kitamura
T
T
Yamada
S
S
Ohta
K
K
Yamashita
M
M
Yasuda
Y
Y
Fujii-Kuriyama
D000818:Animals; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004785:Environmental Pollutants / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D014968:Xanthine Dehydrogenase / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism*
D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase