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Pyrazole is oxidized to 4-hydroxypyrazole by rat liver microsomes in a cytochrome P-450-dependent reaction and this oxidation can be increased by prior treatment of rats with pyrazole, 4-methylpyrazole, or chronic ethanol feeding. The induction pattern suggests that pyrazole may be an effective substrate for oxidation by P-450 IIE.1. This P-450 isozyme is recognized by antibody (anti-3a IgG) raised against the ethanol-inducible P-450 in rabbits. Experiments were carried out to evaluate the ability of anti-3a IgG to inhibit pyrazole oxidation by microsomes from controls and from rats treated with inducers of P-450 IIE.1. Immunoblots with anti-3a IgG or with the anti-pyrazole P-450 IgG were identical and indicated increased staining of the pyrazole P-450 with microsomes from rats treated with pyrazole, 4-methylpyrazole, or ethanol, relative to saline controls; very little staining occurred with microsomes from pair-fed controls or phenobarbital-treated rats. Rates of pyrazole oxidation were highest with microsomes from rats treated with the inducers of P-450 IIE.1 and lowest with pair-fed controls or rats treated with phenobarbital. Anti-3a IgG produced about a 60% decrease of pyrazole oxidation in microsomes from rats treated with inducers of P-450 IIE.1 and about a 25% decrease with the saline controls; no inhibition was found with microsomes from the phenobarbital-treated rats. The anti-3a IgG-resistant rate of pyrazole oxidation was similar with all the microsomal preparations, and was not due to interaction of pyrazole with hydroxyl radicals.(ABSTRACT TRUNCATED AT 250 WORDS)
L A Clejan, and
D R Koop, and
A I Cederbaum
May 1986,
Archives of biochemistry and biophysics,
L A Clejan, and
D R Koop, and
A I Cederbaum
January 1983,
Pharmacology, biochemistry, and behavior,
L A Clejan, and
D R Koop, and
A I Cederbaum
April 1986,
Molecular pharmacology,
L A Clejan, and
D R Koop, and
A I Cederbaum
February 1987,
Proceedings of the National Academy of Sciences of the United States of America,
L A Clejan, and
D R Koop, and
A I Cederbaum
October 1984,
Biochemical and biophysical research communications,
L A Clejan, and
D R Koop, and
A I Cederbaum
January 1980,
Advances in experimental medicine and biology,
L A Clejan, and
D R Koop, and
A I Cederbaum
July 1985,
Biochemical pharmacology,
L A Clejan, and
D R Koop, and
A I Cederbaum
April 1985,
FEBS letters,
L A Clejan, and
D R Koop, and
A I Cederbaum
April 1989,
Biochemical pharmacology,
L A Clejan, and
D R Koop, and
A I Cederbaum
November 1988,
Biochemical and biophysical research communications,
