Induction of rat liver cytochrome P450 isoenzymes CYP 1A and CYP 2B by different fungicides, nitrofurans, and quercetin.
The genotoxic activity of environmental xenobiotics is manifested either in their direct interaction with cellular genetic material or in provoking secondary events, among which reactive oxygen species (ROS) production is a common phenomenon. Both pathways can be mediated by the activity of the cytochrome P450 monooxygenase system. We studied induction of the CYP 1A or CYP 2B monooxygenases in rat liver by the fungicides: thiram, captan, captafol, dodine and the drugs: nitrofurazone, furazolidone and the plant flavonoid: quercetin. A cytochrome P450 induction assay (CYPIA test) was used. S9 prepared from livers of rats treated with the test compounds were used to activate ethidium bromide (EtBr) (CYP 1A isoenzyme) or cyclophosphamide (CPA) (CYP 2B isoenzyme) in the Ames test. It was found that among the tested compounds, the most potent inducer of CYP 1A was furazolidone (3 x 80 mg/kg). Less potent was thiram (1 x 100mg/kg), as well as quercetin (3 x 80 mg/kg), and captafol (1 x 30 mg/kg). On the other hand, thiram (1 x 100 mg/kg), captafol (1 x 30 mg/kg), and quercetin (3 x 80 mg/kg) were most potent in the CYP 2B isoenzyme induction, while furazolidone (3 x 80 mg/kg), and nitrofurazone (3 x 80 mg/kg) appeared to be less potent in this respect. Captan and dodine (3 x 80 mg/kg) did not affect the activity of any of the cytochrome P450 isoenzymes.
Rahden-Staron
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Department of Biochemistry, Medical University of Warsaw, ul. Banacha 1, 02-097 Warszawa, Poland. ivrahden@amwaw.edu.pl
Czeczot
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Szumilo
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D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D004996:Ethidium / Q000494:pharmacology; D005659:Fungicides, Industrial / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D009152:Mutagenicity Tests; D009581:Nitrofurans / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D002273:Carcinogens; D005659:Fungicides, Industrial; D007527:Isoenzymes; D009581:Nitrofurans; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D011794:Quercetin; D004996:Ethidium; D010634:Phenobarbital