Relationship between the murine Ah locus and 2,3,7,8-tetrachlorodibenzo-p-dioxin hepatic metabolism, enzyme induction, and toxicity
The influence of the Ah locus and hepatic microsomal enzyme induction on 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) metabolism and hepatotoxicity was investigated using C57BL/6J (C57) and DBA/2J (DBA) mice. C57 mice are more sensitive to toxic and enzyme inductive effects of 2,3,7,8-TCDD than DBA mice. Characterization of interstrain differences in hepatic enzyme induction, 2,3,7,8-TCDD metabolism, and hepatotoxicity may aid in identifying the mechanism(s) of 2,3,7,8-TCDD toxicity. The hepatic uptake and metabolism of ({sup 14}C)2,3,7,8-TCDD were studied using isolated hepatocytes from control and 2,3,7,8-TCDD-pretreated C57 and DBA mice. Pretreated mice were injected with 2,3,7,8-TCDD at doses that maximally induce aryl hydrocarbon hydroxylase activity or at doses that approach the LD{sub 50} value. Despite the induction of hepatic 7-ethoxyresorufin O-deethylase activity and benzo(a)pyrene metabolism, all 2,3,7,8-TCDD pretreatment doses failed to increase the rate of ({sup 14}C)2,3,7,8-TCDD metabolism for both C57 and DBA mice. These results suggest that the uptake and rate of hepatic metabolism of 2,3,7,8-TCDD do not correlate with genetic differences at the murine Ah locus.
- Research Organization:
- State Univ. of New York, Buffalo, NY (USA)
- OSTI ID:
- 5645056
- Country of Publication:
- United States
- Language:
- English
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560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
AROMATICS
BENZOPYRENE
BODY
CARBON 14 COMPOUNDS
CELL CONSTITUENTS
CONDENSED AROMATICS
DIGESTIVE SYSTEM
DIOXIN
ENZYME ACTIVITY
ENZYME INDUCTION
ENZYMES
GENE REGULATION
GLANDS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
HYDROXYLASES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIVER
MAMMALS
METABOLISM
MICE
MICROSOMES
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANOIDS
ORGANS
OXIDOREDUCTASES
RIBOSOMES
RODENTS
TOXICITY
TRACER TECHNIQUES
VERTEBRATES