Biomaterial Database

Chlorophenoxyacid herbicides induce microsomal cytochrome P-450 IVA1 (P-452) in rat liver. 1988

M A Bacher, and G G Gibson

Department of Biochemistry, University of Surrey, Guildford, U.K.

Induction of the cytochrome P-450 mixed-function oxidase and specifically the cytochrome P-450 IVA1 isoenzyme by seven phenoxyacid herbicides in rat liver have been studied. Liver microsomes from rats orally treated with the herbicides at 3 dose levels showed a significant increase in total cytochrome P-450 content with 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) being the most potent inducer. Benzphetamine N-demethylation, as a marker of cytochrome P-450b (P-450 IIB1) activity, was not affected by any of the herbicides studied, whereas cytochrome P-450c (P-450 IA1), as assayed by ethoxyresorufin-O-deethylation activity, was significantly increased (up to 2.2-fold) by some of the herbicides. The 12-hydroxylation of lauric acid was significantly induced (3-8-fold) by all seven herbicides, 4-chlorophenoxyacetic acid (CPA) and 2,4,5-trichlorophenoxypropionic acid (2,4,5-TP) being the weakest and most potent inducers respectively. This increase in lauric acid 12-hydroxylase activity was accompanied by an increase in the hepatic content of cytochrome P-450 IVA1 as assessed by both a qualitative Western blot procedure and a quantitative ELISA method. By comparison, lauric acid 11-hydroxylase activity was not or only marginally increased by phenoxyacid herbicide pretreatment. Our results suggest that the phenoxyacid herbicides act as mixed inducers of the cytochrome P-450 mixed function oxidase system, preferentially inducing the cytochrome P-450 IVA1 isoenzyme.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008862	Microsomes, Liver	Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.	Liver Microsomes,Liver Microsome,Microsome, Liver
D009929	Organ Size	The measurement of an organ in volume, mass, or heaviness.	Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D002733	Chlorophenols	Phenols substituted with one or more chlorine atoms in any position.	Chlorophenol,Hydroxychlorobenzenes
D003577	Cytochrome P-450 Enzyme System	A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.	Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D004790	Enzyme Induction	An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.	Induction, Enzyme
D006016	Glycolates	Derivatives of ACETIC ACID which contain an hydroxy group attached to the methyl carbon.	2-Hydroxyacetates,Glycolate Ethers,Hydroxyacetate Ethers,Hydroxyacetates,Hydroxyacetic Acids,2 Hydroxyacetates,Acids, Hydroxyacetic,Ethers, Glycolate,Ethers, Hydroxyacetate
D006540	Herbicides	Pesticides used to destroy unwanted vegetation, especially various types of weeds, grasses (POACEAE), and woody plants. Some plants develop HERBICIDE RESISTANCE.	Algaecide,Algicide,Herbicide,Algaecides,Algicides
D006899	Mixed Function Oxygenases	Widely distributed enzymes that carry out oxidation-reduction reactions in which one atom of the oxygen molecule is incorporated into the organic substrate; the other oxygen atom is reduced and combined with hydrogen ions to form water. They are also known as monooxygenases or hydroxylases. These reactions require two substrates as reductants for each of the two oxygen atoms. There are different classes of monooxygenases depending on the type of hydrogen-providing cosubstrate (COENZYMES) required in the mixed-function oxidation.	Hydroxylase,Hydroxylases,Mixed Function Oxidase,Mixed Function Oxygenase,Monooxygenase,Monooxygenases,Mixed Function Oxidases,Function Oxidase, Mixed,Function Oxygenase, Mixed,Oxidase, Mixed Function,Oxidases, Mixed Function,Oxygenase, Mixed Function,Oxygenases, Mixed Function
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia