Synergistic induction of rat microsomal CYP1A1 and CYP1A2 by acetone in combination with pyridine.
The effect of exposure to acetone, pyridine or acetone in combination with pyridine on microsomal CYP1A1, CYP1A2 and CYP2E1 levels and their catalytic activities was determined in the rat. CYP1A1 and CYP1A2 in the liver and CYP1A1 in the lung were induced along with their catalytic activities by either pyridine, acetone or acetone and pyridine. The induction by acetone and pyridine was greater than the additive effect of both compounds, indicating synergism. Acetone, pyridine or both compounds induced CYP2E1 protein to the same extent in the liver and lung. However, induction of CYP2E1 protein was accompanied by induction of its catalytic activity in the liver but not in the lung. This is the first reported induction of CYP1A proteins and catalytic activities (a) by acetone and (b) synergistically by xenobiotics.
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Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ 08855-1179.
Bennett
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Storch
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Ghosal
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Thomas
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PE
D000096:Acetone / Q000633:toxicity*; D000818:Animals; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects*; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010088:Oxidoreductases / Q000378:metabolism*; D011725:Pyridines / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D011725:Pyridines; D000096:Acetone; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1