Effect of inducers of monooxygenase activity on the hepatic metabolism of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by the rat and hamster

Journal Article · Tue Mar 04 23:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6829917

Wroblewski, V J; Olson, J R

The induction of cytochrome P-450 enzymes and their role of the metabolism of TCDD as examined in the rat and hamster. TCDD metabolism was assessed by incubating purified /sup 14/C-TCDD (2.2..mu..M) with suspensions of isolated hepatocytes from untreated, TCDD, 3-methylcholanthrene (3-MC), isosafrole or phenobarbital (PB) pretreated animals. In addition, the metabolism of benzo(a)pyrene (BaP) and 7-ethoxyresorufin(7-ER), substrates for cytochrome P-448, were measured in hepatocytes and microsomes prepared from these animals. TCDD and 3-MC pretreatments resulted in a 5 to 6-fold increase in the rate of TCDD metabolism by hepatocytes from both species. However, PB had no effect on TCDD metabolism in either species. Pretreatment with isosafrole did not alter TCDD metabolism in the hamster, but doubled the rate in rat hepatocytes. In the rat, the effect of the inducers on BaP and 7-ER metabolism was similar to their effect on TCDD metabolism. In contrast, TCDD, 3-MC and isosafrole did not increase the metabolism of BaP or 7-ER in hamster hepatocytes or microsomes. However, PB more than doubled BaP metabolism while having no effect on 7-ER or TCDD metabolism. The results indicate that TCDD is metabolized by a polycyclic hydrocarbon inducible isozyme of P-450 in both the rat and hamster. However, the results suggest that the inducibility and/or substrate specificity of P-450 isozymes differ in these two species.

• Research Organization: State Univ. of New York, Buffalo
• OSTI ID: 6829917
• Report Number(s): CONF-8604222-
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:4; ISSN FEPRA
• Country of Publication: United States
• Language: English

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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
BENZOPYRENE
BIOLOGICAL EFFECTS
CARBON 14 COMPOUNDS
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CONDENSED AROMATICS
DIOXIN
DRUGS
ENZYMES
HAMSTERS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
HYPNOTICS AND SEDATIVES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIVER CELLS
MAMMALS
METABOLISM
MICROSOMES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANOIDS
OXIDOREDUCTASES
OXYGENASES
PHENOBARBITAL
POLYCYCLIC AROMATIC HYDROCARBONS
PYRIMIDINES
RATS
RODENTS
SOMATIC CELLS
TRACER TECHNIQUES
VERTEBRATES