Relationship between murine Ah phenotype and the hepatic metabolism of 2,3,7,8-tetrachlorodibenzo-P-dioxin (TCDD)
The Ah receptor has been correlated with the toxic effects of TCDD in C57BL/6J (B6) and DBA/2J (D2) mice. The B6 strain, which has a high affinity cytosolic Ah receptor, is more sensitive to TCDD than the D2 strain, which lacks this receptor. The metabolism of TCDD was studied by incubating /sup 14/C-TCDD (2.2 ..mu..M) with hepatocytes from control and TCDD-pretreated B6 and D2 mice. Mice were pretreated with TCDD at doses that maximally induce ethoxyresorufin-O-deethylase (EROD) activity, a measure of Ah locus responsiveness to TCDD (B6, 3..mu..g/kg, ip;D2, 30..mu..g/kg, ip). Similar cytochrome P-450 content was detected in control B6 and D2 hepatocytes, however, TCDD pretreatment increased P-450 content 400% in B6 and 300% in D2 mice. No difference in hepatic EROD activity was found between control B6 and D2 mice (81.7 and 101.7 pmol/min/nmol P-450, respectively), but EROD activity was increased 17-fold in B6 and 10-fold in D2 mice after TCDD administration. The average rate of hepatic TCDD metabolism over two hours was similar in control B6 and D2 mice (1.103 and 0.945 pmol/hr/mg cell protein, respectively), although some qualitative differences in the metabolites were detected by HPLC. TCDD pretreatment produced no quantitative or qualitative changes in TCDD metabolism. These results suggest that the rate of hepatic TCDD metabolism does not correlate with genetic differences at the Ah locus.
- Research Organization:
- State Univ. of New York, Buffalo
- OSTI ID:
- 7024965
- Report Number(s):
- CONF-8604222-; TRN: 87-011179
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:4; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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DIOXIN
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TOXICITY
OXIDOREDUCTASES
ENZYME ACTIVITY
BIOLOGICAL VARIABILITY
CARBON 14 COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
LIVER
MICE
PHENOTYPE
RECEPTORS
ANIMALS
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CHROMATOGRAPHY
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LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
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ORGANIC OXYGEN COMPOUNDS
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