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Hepatic metabolism of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the rat and guinea pig

Journal Article · · Toxicol. Appl. Pharmacol.; (United States)
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Marked interspecies variability exists in the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), with the rat having an LD/sub 50/ about 25-fold greater than the guinea pig. The metabolism of TCDD was examined by incubating hepatocytes isolated from these animals with purified (/sup 14/C)TCDD (2.2 microM) for 8 hr. Over the 8-hr incubation, cytochrome P-450 content and ethoxyresorufin O-deethylase and benzphetamine N-demethylase activities were well maintained, indicating the functional viability of the hepatocytes. Quantitative differences were observed in the rate of (/sup 14/C)TCDD metabolism, with hepatocytes from control rats metabolizing TCDD at a rate 2.8-fold greater than hepatocytes from control guinea pigs. The role of the hepatic cytochrome P-450-448-dependent monooxygenase system in the metabolism of TCDD was examined through the use of hepatocytes isolated from animals pretreated with either TCDD or phenobarbital. The rate of (/sup 14/C)TCDD metabolite formation in hepatocytes from TCDD pretreated guinea pigs (0.26 +/- 0.14 pmol mg cell protein-1 hr-1) was unchanged from the control rate, while the rate in hepatocytes from TCDD pretreated rats was 3.2-fold greater than control and nine times greater than in hepatocytes from TCDD-pretreated guinea pigs. On the other hand, phenobarbital pretreatment produced little change in the rate of (/sup 14/C)TCDD metabolism in rat hepatocytes. These results suggest that TCDD may be metabolized by a TCDD inducible form of cytochrome P-448 which is expressed in the rat but not in the guinea pig.

Research Organization:
SUNY, Buffalo
OSTI ID:
6383205
Journal Information:
Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 2; ISSN TXAPA
Country of Publication:
United States
Language:
English

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Related Subjects

550201 -- Biochemistry-- Tracer Techniques
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANESTHETICS
ANIMAL CELLS
ANIMALS
ANTICONVULSANTS
AROMATICS
AZINES
BARBITURATES
BODY
CARBON 14 COMPOUNDS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHLORINATED AROMATIC HYDROCARBONS
CYTOCHROMES
DIGESTIVE SYSTEM
DIOXIN
DRUGS
ENZYMES
GLANDS
GUINEA PIGS
HALOGENATED AROMATIC HYDROCARBONS
HETEROCYCLIC COMPOUNDS
HYPNOTICS AND SEDATIVES
LABELLED COMPOUNDS
LIVER
LIVER CELLS
MAMMALS
METABOLISM
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
OXIDOREDUCTASES
PHENOBARBITAL
PIGMENTS
PROTEINS
PYRIMIDINES
RATS
RODENTS
SOMATIC CELLS
TOXICITY
VERTEBRATES