Cytochrome P-450 CYP3A: A cytochrome P-450 suptype that has specificity for a broad variety of lipophilic compounds, including STEROIDS; FATTY ACIDS; and XENOBIOTICS. This enzyme has clinical significance due to its ability to metabolize a diverse array of clinically important drugs such as CYCLOSPORINE; VERAPAMIL; and MIDAZOLAM. This enzyme also catalyzes the N-demethylation of ERYTHROMYCIN.Cytochrome P-450 CYP2D6: A cytochrome P450 enzyme that catalyzes the hydroxylation of many drugs and environmental chemicals, such as DEBRISOQUINE; ADRENERGIC RECEPTOR ANTAGONISTS; and TRICYCLIC ANTIDEPRESSANTS. This enzyme is deficient in up to 10 percent of the Caucasian population.Cytochrome P-450 CYP1A1: A liver microsomal cytochrome P-450 monooxygenase capable of biotransforming xenobiotics such as polycyclic hydrocarbons and halogenated aromatic hydrocarbons into carcinogenic or mutagenic compounds. They have been found in mammals and fish. This enzyme, encoded by CYP1A1 gene, can be measured by using ethoxyresorufin as a substrate for the ethoxyresorufin O-deethylase activity.Cytochrome P-450 CYP1A2: A cytochrome P450 enzyme subtype that has specificity for relatively planar heteroaromatic small molecules, such as CAFFEINE and ACETAMINOPHEN.Aryl Hydrocarbon Hydroxylases: A large group of cytochrome P-450 (heme-thiolate) monooxygenases that complex with NAD(P)H-FLAVIN OXIDOREDUCTASE in numerous mixed-function oxidations of aromatic compounds. They catalyze hydroxylation of a broad spectrum of substrates and are important in the metabolism of steroids, drugs, and toxins such as PHENOBARBITAL, carcinogens, and insecticides.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 CYP2B1: A major cytochrome P-450 enzyme which is inducible by PHENOBARBITAL in both the LIVER and SMALL INTESTINE. It is active in the metabolism of compounds like pentoxyresorufin, TESTOSTERONE, and ANDROSTENEDIONE. This enzyme, encoded by CYP2B1 gene, also mediates the activation of CYCLOPHOSPHAMIDE and IFOSFAMIDE to MUTAGENS.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.Microsomes, Liver: Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.Steroid Hydroxylases: Cytochrome P-450 monooxygenases (MIXED FUNCTION OXYGENASES) that are important in steroid biosynthesis and metabolism.Hydroxylation: Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)Steroid 16-alpha-Hydroxylase: A liver microsomal cytochrome P450 enzyme that catalyzes the 16-alpha-hydroxylation of a broad spectrum of steroids, fatty acids, and xenobiotics in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme is encoded by a number of genes from several CYP2 subfamilies.Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.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.Dealkylation: The removing of alkyl groups from a compound. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Midazolam: A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH.Polymorphism, Genetic: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Dextromethorphan: Methyl analog of DEXTRORPHAN that shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is an NMDA receptor antagonist (RECEPTORS, N-METHYL-D-ASPARTATE) and acts as a non-competitive channel blocker. It is one of the widely used ANTITUSSIVES, and is also used to study the involvement of glutamate receptors in neurotoxicity.Steroid 17-alpha-Hydroxylase: A microsomal cytochrome P450 enzyme that catalyzes the 17-alpha-hydroxylation of progesterone or pregnenolone and subsequent cleavage of the residual two carbons at C17 in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP17 gene, generates precursors for glucocorticoid, androgen, and estrogen synthesis. Defects in CYP17 gene cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL) and abnormal sexual differentiation.Chlorzoxazone: A centrally acting central muscle relaxant with sedative properties. It is claimed to inhibit muscle spasm by exerting an effect primarily at the level of the spinal cord and subcortical areas of the brain. (From Martindale, The Extra Pharmacopoea, 30th ed, p1202)Mephenytoin: An anticonvulsant effective in tonic-clonic epilepsy (EPILEPSY, TONIC-CLONIC). It may cause blood dyscrasias.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Receptors, Aryl Hydrocarbon: Cytoplasmic proteins that bind certain aryl hydrocarbons, translocate to the nucleus, and activate transcription of particular DNA segments. AH receptors are identified by their high-affinity binding to several carcinogenic or teratogenic environmental chemicals including polycyclic aromatic hydrocarbons found in cigarette smoke and smog, heterocyclic amines found in cooked foods, and halogenated hydrocarbons including dioxins and polychlorinated biphenyls. No endogenous ligand has been identified, but an unknown natural messenger with a role in cell differentiation and development is suspected.Alkane 1-Monooxygenase: A P450 oxidoreductase that catalyzes the hydroxylation of the terminal carbon of linear hydrocarbons such as octane and FATTY ACIDS in the omega position. The enzyme may also play a role in the oxidation of a variety of structurally unrelated compounds such as XENOBIOTICS, and STEROIDS.Hepatocytes: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Tetrachlorodibenzodioxin: A chemical by-product that results from burning or incinerating chlorinated industrial chemicals and other hydrocarbons. This compound is considered an environmental toxin, and may pose reproductive, as well as, other health risks for animals and humans.Cholestanetriol 26-Monooxygenase: An NAPH-dependent cytochrome P450 enzyme that catalyzes the oxidation of the side chain of sterol intermediates such as the 27-hydroxylation of 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol.Steroid 21-Hydroxylase: An adrenal microsomal cytochrome P450 enzyme that catalyzes the 21-hydroxylation of steroids in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP21 gene, converts progesterones to precursors of adrenal steroid hormones (CORTICOSTERONE; HYDROCORTISONE). Defects in CYP21 cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL).Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Troleandomycin: A macrolide antibiotic that is similar to ERYTHROMYCIN.Aldosterone Synthase: A mitochondrial cytochrome P450 enzyme that catalyzes the 18-hydroxylation of steroids in the presence of molecular oxygen and NADPH-specific flavoprotein. This enzyme, encoded by CYP11B2 gene, is important in the conversion of CORTICOSTERONE to 18-hydroxycorticosterone and the subsequent conversion to ALDOSTERONE.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Aromatase: An enzyme that catalyzes the desaturation (aromatization) of the ring A of C19 androgens and converts them to C18 estrogens. In this process, the 19-methyl is removed. This enzyme is membrane-bound, located in the endoplasmic reticulum of estrogen-producing cells of ovaries, placenta, testes, adipose, and brain tissues. Aromatase is encoded by the CYP19 gene, and functions in complex with NADPH-FERRIHEMOPROTEIN REDUCTASE in the cytochrome P-450 system.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Receptors, Steroid: Proteins found usually in the cytoplasm or nucleus that specifically bind steroid hormones and trigger changes influencing the behavior of cells. The steroid receptor-steroid hormone complex regulates the transcription of specific genes.Pharmacogenetics: A branch of genetics which deals with the genetic variability in individual responses to drugs and drug metabolism (BIOTRANSFORMATION).Microsomes: Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)NADPH-Ferrihemoprotein Reductase: A flavoprotein that catalyzes the reduction of heme-thiolate-dependent monooxygenases and is part of the microsomal hydroxylating system. EC 22.214.171.124.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Steroid 11-beta-Hydroxylase: A mitochondrial cytochrome P450 enzyme that catalyzes the 11-beta-hydroxylation of steroids in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP11B1 gene, is important in the synthesis of CORTICOSTERONE and HYDROCORTISONE. Defects in CYP11B1 cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL).Metabolic Detoxication, Drug: Reduction of pharmacologic activity or toxicity of a drug or other foreign substance by a living system, usually by enzymatic action. It includes those metabolic transformations that make the substance more soluble for faster renal excretion.Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc.Benzo(a)pyrene: A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke.25-Hydroxyvitamin D3 1-alpha-Hydroxylase: A mitochondrial cytochrome P450 enzyme that catalyzes the 1-alpha-hydroxylation of 25-hydroxyvitamin D3 (also known as 25-hydroxycholecalciferol) in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP27B1 gene, converts 25-hydroxyvitamin D3 to 1-alpha,25-dihydroxyvitamin D3 which is the active form of VITAMIN D in regulating bone growth and calcium metabolism. This enzyme is also active on plant 25-hydroxyvitamin D2 (ergocalciferol).Phenacetin: A phenylacetamide that was formerly used in ANALGESICS but nephropathy and METHEMOGLOBINEMIA led to its withdrawal from the market. (From Smith and Reynard, Textbook of Pharmacology,1991, p431)beta-Naphthoflavone: A polyaromatic hydrocarbon inducer of P4501A1 and P4501A2 cytochromes. (Proc Soc Exp Biol Med 1994 Dec:207(3):302-308)Sulfaphenazole: A sulfonilamide anti-infective agent.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Quinidine: An optical isomer of quinine, extracted from the bark of the CHINCHONA tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular ACTION POTENTIALS, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission.Cholesterol 7-alpha-Hydroxylase: A membrane-bound cytochrome P450 enzyme that catalyzes the 7-alpha-hydroxylation of CHOLESTEROL in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP7, converts cholesterol to 7-alpha-hydroxycholesterol which is the first and rate-limiting step in the synthesis of BILE ACIDS.14-alpha Demethylase Inhibitors: Compounds that specifically inhibit STEROL 14-DEMETHYLASE. A variety of azole-derived ANTIFUNGAL AGENTS act through this mechanism.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Coumarins: Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.Vitamin K Epoxide Reductases: OXIDOREDUCTASES which mediate vitamin K metabolism by converting inactive vitamin K 2,3-epoxide to active vitamin K.Phenobarbital: A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.Gene Frequency: The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Dextrorphan: Dextro form of levorphanol. It acts as a noncompetitive NMDA receptor antagonist, among other effects, and has been proposed as a neuroprotective agent. It is also a metabolite of DEXTROMETHORPHAN.Metabolic Detoxication, Phase I: Functionalization of exogenous substances to prepare them for conjugation in PHASE II DETOXIFICATION. Phase I enzymes include CYTOCHROME P450 enzymes and some OXIDOREDUCTASES. Excess induction of phase I over phase II detoxification leads to higher levels of FREE RADICALS that can induce CANCER and other cell damage. Induction or antagonism of phase I detoxication is the basis of a number of DRUG INTERACTIONS.Receptors, Cytoplasmic and Nuclear: Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.Cholesterol Side-Chain Cleavage Enzyme: A mitochondrial cytochrome P450 enzyme that catalyzes the side-chain cleavage of C27 cholesterol to C21 pregnenolone in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP11A1 gene, catalyzes the breakage between C20 and C22 which is the initial and rate-limiting step in the biosynthesis of various gonadal and adrenal steroid hormones.Area Under Curve: A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992)Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Hydroxytestosterones: 17 beta-Hydroxy-4-androsten-3-ones. Testosterone derivatives formed by the substitution of one or more hydroxyl groups in any position.Benzoflavones: Organic compounds containing a BENZENE ring attached to a flavone group. Some of these are potent arylhydrocarbon hydroxylase inhibitors. They may also inhibit the binding of NUCLEIC ACIDS to BENZOPYRENES and related compounds. The designation includes all isomers; the 7,8-isomer is most frequently encountered.Herb-Drug Interactions: The effect of herbs, other PLANTS, or PLANT EXTRACTS on the activity, metabolism, or toxicity of drugs.Adrenal Hyperplasia, Congenital: A group of inherited disorders of the ADRENAL GLANDS, caused by enzyme defects in the synthesis of cortisol (HYDROCORTISONE) and/or ALDOSTERONE leading to accumulation of precursors for ANDROGENS. Depending on the hormone imbalance, congenital adrenal hyperplasia can be classified as salt-wasting, hypertensive, virilizing, or feminizing. Defects in STEROID 21-HYDROXYLASE; STEROID 11-BETA-HYDROXYLASE; STEROID 17-ALPHA-HYDROXYLASE; 3-beta-hydroxysteroid dehydrogenase (3-HYDROXYSTEROID DEHYDROGENASES); TESTOSTERONE 5-ALPHA-REDUCTASE; or steroidogenic acute regulatory protein; among others, underlie these disorders.Hydroxyeicosatetraenoic Acids: Eicosatetraenoic acids substituted in any position by one or more hydroxy groups. They are important intermediates in a series of biosynthetic processes leading from arachidonic acid to a number of biologically active compounds such as prostaglandins, thromboxanes, and leukotrienes.Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.Debrisoquin: An adrenergic neuron-blocking drug similar in effects to GUANETHIDINE. It is also noteworthy in being a substrate for a polymorphic cytochrome P-450 enzyme. Persons with certain isoforms of this enzyme are unable to properly metabolize this and many other clinically important drugs. They are commonly referred to as having a debrisoquin 4-hydroxylase polymorphism.Kinetics: The rate dynamics in chemical or physical systems.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Methoxsalen: A naturally occurring furocoumarin compound found in several species of plants, including Psoralea corylifolia. It is a photoactive substance that forms DNA ADDUCTS in the presence of ultraviolet A irradiation.Glutathione Transferase: A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Triazolam: A short-acting benzodiazepine used in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries.Stereoisomerism: The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form.8,11,14-Eicosatrienoic Acid: A 20-carbon-chain fatty acid, unsaturated at positions 8, 11, and 14. It differs from arachidonic acid, 5,8,11,14-eicosatetraenoic acid, only at position 5.Testosterone: A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.Rifampin: A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160)DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Cytochromes b5: Cytochromes of the b group that are found bound to cytoplasmic side of ENDOPLASMIC RETICULUM. They serve as electron carrier proteins for a variety of membrane-bound OXYGENASES. They are reduced by the enzyme CYTOCHROME-B(5) REDUCTASE.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Lauric Acids: 12-Carbon saturated monocarboxylic acids.Asian Continental Ancestry Group: Individuals whose ancestral origins are in the southeastern and eastern areas of the Asian continent.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Oxazines: Six-membered heterocycles containing an oxygen and a nitrogen.Hep G2 Cells: A human liver tumor cell line used to study a variety of liver-specific metabolic functions.SkatolePolymorphism, Restriction Fragment Length: Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment.Steroid 12-alpha-Hydroxylase: A liver microsomal cytochrome P450 enzyme that catalyzes the 12-alpha-hydroxylation of a broad spectrum of sterols in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP8B1gene, converts 7-alpha-hydroxy-4-cholesten-3-one to 7-alpha-12-alpha-dihydroxy-4-cholesten-3-one and is required in the synthesis of BILE ACIDS from cholesterol.Carcinogens: Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.P-Glycoprotein: A 170-kDa transmembrane glycoprotein from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many ANTINEOPLASTIC AGENTS. Overexpression of this glycoprotein is associated with multidrug resistance (see DRUG RESISTANCE, MULTIPLE).Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Glucuronosyltransferase: A family of enzymes accepting a wide range of substrates, including phenols, alcohols, amines, and fatty acids. They function as drug-metabolizing enzymes that catalyze the conjugation of UDPglucuronic acid to a variety of endogenous and exogenous compounds. EC 126.96.36.199.Citrus paradisi: A plant species of the genus CITRUS, family RUTACEAE that produces the familiar grapefruit. There is evidence that grapefruit inhibits CYTOCHROME P-450 CYP3A4, resulting in delayed metabolism and higher blood levels of a variety of drugs.Oxygenases: Oxidases that specifically introduce DIOXYGEN-derived oxygen atoms into a variety of organic molecules.Fluvoxamine: A selective serotonin reuptake inhibitor that is used in the treatment of DEPRESSION and a variety of ANXIETY DISORDERS.Psoralens: Linear furanocoumarins which are found in many PLANTS, especially UMBELLIFERAE and RUTACEAE, as well as PSORALEA from which they were originally discovered. They can intercalate DNA and, in an UV-initiated reaction of the furan portion, alkylate PYRIMIDINES, resulting in PHOTOSENSITIVITY DISORDERS.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Methylcholanthrene: A carcinogen that is often used in experimental cancer studies.Xanthomatosis, Cerebrotendinous: An autosomal recessive lipid storage disorder due to mutation of the gene CYP27A1 encoding a CHOLESTANETRIOL 26-MONOOXYGENASE. It is characterized by large deposits of CHOLESTEROL and CHOLESTANOL in various tissues resulting in xanthomatous swelling of tendons, early CATARACT, and progressive neurological symptoms.Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt.Omeprazole: A 4-methoxy-3,5-dimethylpyridyl, 5-methoxybenzimidazole derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits an H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS.Genetic Variation: Genotypic differences observed among individuals in a population.Metabolic Clearance Rate: Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site.Arylamine N-Acetyltransferase: An enzyme that catalyzes the transfer of acetyl groups from ACETYL-COA to arylamines. It can also catalyze acetyl transfer between arylamines without COENZYME A and has a wide specificity for aromatic amines, including SEROTONIN. However, arylamine N-acetyltransferase should not be confused with the enzyme ARYLALKYLAMINE N-ACETYLTRANSFERASE which is also referred to as SEROTONIN ACETYLTRANSFERASE.Polycyclic Hydrocarbons, Aromatic: A major group of unsaturated cyclic hydrocarbons containing two or more rings. The vast number of compounds of this important group, derived chiefly from petroleum and coal tar, are rather highly reactive and chemically versatile. The name is due to the strong and not unpleasant odor characteristic of most substances of this nature. (From Hawley's Condensed Chemical Dictionary, 12th ed, p96)Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Azoles: Five membered rings containing a NITROGEN atom.Butyrophenones: Compounds containing phenyl-1-butanone.TriazolesHaplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX.Oxidoreductases, O-Demethylating: Drug metabolizing enzymes which oxidize methyl ethers. Usually found in liver microsomes.Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Bupropion: A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment.Tolbutamide: A sulphonylurea hypoglycemic agent with actions and uses similar to those of CHLORPROPAMIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290)Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.Aryl Hydrocarbon Receptor Nuclear Translocator: Aryl hydrocarbon receptor nuclear translocator is a basic HELIX-LOOP-HELIX MOTIF containing protein that forms a complex with DIOXIN RECEPTOR. The complex binds xenobiotic regulatory elements and activates transcription of a variety of genes including UDP GLUCURONOSYLTRANSFERASE. AhR nuclear translocator is also a subunit of HYPOXIA-INDUCIBLE FACTOR 1.Biocatalysis: The facilitation of biochemical reactions with the aid of naturally occurring catalysts such as ENZYMES.Insects: The class Insecta, in the phylum ARTHROPODA, whose members are characterized by division into three parts: head, thorax, and abdomen. They are the dominant group of animals on earth; several hundred thousand different kinds having been described. Three orders, HEMIPTERA; DIPTERA; and SIPHONAPTERA; are of medical interest in that they cause disease in humans and animals. (From Borror et al., An Introduction to the Study of Insects, 4th ed, p1)Oxidoreductases: The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Hypericum: Genus of perennial plants in the family CLUSIACEAE (sometimes classified as Hypericaceae). Herbal and homeopathic preparations are used for depression, neuralgias, and a variety of other conditions. Hypericum contains flavonoids; GLYCOSIDES; mucilage, TANNINS; volatile oils (OILS, ESSENTIAL), hypericin and hyperforin.Phenytoin: An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs.Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.Perazine: A phenothiazine antipsychotic with actions and uses similar to those of CHLORPROMAZINE. Extrapyramidal symptoms may be more common than other side effects.Clotrimazole: An imidazole derivative with a broad spectrum of antimycotic activity. It inhibits biosynthesis of the sterol ergostol, an important component of fungal CELL MEMBRANES. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane.Cyclophilins: A family of peptidyl-prolyl cis-trans isomerases that bind to CYCLOSPORINS and regulate the IMMUNE SYSTEM. EC 5.2.1.-Polychlorinated Biphenyls: Industrial products consisting of a mixture of chlorinated biphenyl congeners and isomers. These compounds are highly lipophilic and tend to accumulate in fat stores of animals. Many of these compounds are considered toxic and potential environmental pollutants.Epoxide Hydrolases: Enzymes that catalyze reversibly the formation of an epoxide or arene oxide from a glycol or aromatic diol, respectively.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of PHENYTOIN; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar.Mass Spectrometry: An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.Homozygote: An individual in which both alleles at a given locus are identical.Dioxins: Chlorinated hydrocarbons containing heteroatoms that are present as contaminants of herbicides. Dioxins are carcinogenic, teratogenic, and mutagenic. They have been banned from use by the FDA.Hepatocyte Nuclear Factor 4: A subfamily of nuclear receptors that regulate GENETIC TRANSCRIPTION of a diverse group of GENES involved in the synthesis of BLOOD COAGULATION FACTORS; and in GLUCOSE; CHOLESTEROL; and FATTY ACIDS metabolism.DNA Adducts: The products of chemical reactions that result in the addition of extraneous chemical groups to DNA.Ticlopidine: An effective inhibitor of platelet aggregation commonly used in the placement of STENTS in CORONARY ARTERIES.Fundulidae: Family of small, surface-dwelling fish that inhabit fresh and brackish waters, and coastal marine areas.Receptors, Calcitriol: Proteins, usually found in the cytoplasm, that specifically bind calcitriol, migrate to the nucleus, and regulate transcription of specific segments of DNA with the participation of D receptor interacting proteins (called DRIP). Vitamin D is converted in the liver and kidney to calcitriol and ultimately acts through these receptors.Benzoxazines: OXAZINES with a fused BENZENE ring.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.Cross-Over Studies: Studies comparing two or more treatments or interventions in which the subjects or patients, upon completion of the course of one treatment, are switched to another. In the case of two treatments, A and B, half the subjects are randomly allocated to receive these in the order A, B and half to receive them in the order B, A. A criticism of this design is that effects of the first treatment may carry over into the period when the second is given. (Last, A Dictionary of Epidemiology, 2d ed)Intestines: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.Gemfibrozil: A lipid-regulating agent that lowers elevated serum lipids primarily by decreasing serum triglycerides with a variable reduction in total cholesterol.Steroids: A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Arylsulfotransferase: A sulfotransferase that catalyzes the sulfation of a phenol in the presence of 3'-phosphoadenylylsulfate as sulfate donor to yield an aryl sulfate and adenosine 3',5'-bisphosphate. A number of aromatic compounds can act as acceptors; however, organic hydroxylamines are not substrates. Sulfate conjugation by this enzyme is a major pathway for the biotransformation of phenolic and catechol drugs as well as neurotransmitters. EC 188.8.131.52.Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes.Cell Line, Tumor: A cell line derived from cultured tumor cells.Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling.European Continental Ancestry Group: Individuals whose ancestral origins are in the continent of Europe.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Glucosinolates: Substituted thioglucosides. They are found in rapeseed (Brassica campestris) products and related cruciferae. They are metabolized to a variety of toxic products which are most likely the cause of hepatocytic necrosis in animals and humans.Itraconazole: A triazole antifungal agent that inhibits cytochrome P-450-dependent enzymes required for ERGOSTEROL synthesis.5' Flanking Region: The region of DNA which borders the 5' end of a transcription unit and where a variety of regulatory sequences are located.2-Pyridinylmethylsulfinylbenzimidazoles: Compounds that contain benzimidazole joined to a 2-methylpyridine via a sulfoxide linkage. Several of the compounds in this class are ANTI-ULCER AGENTS that act by inhibiting the POTASSIUM HYDROGEN ATPASE found in the PROTON PUMP of GASTRIC PARIETAL CELLS.Nortriptyline: A metabolite of AMITRIPTYLINE that is also used as an antidepressive agent. Nortriptyline is used in major depression, dysthymia, and atypical depressions.Allyl CompoundsEnvironmental Pollutants: Substances or energies, for example heat or light, which when introduced into the air, water, or land threaten life or health of individuals or ECOSYSTEMS.Calcifediol: The major circulating metabolite of VITAMIN D3. It is produced in the LIVER and is the best indicator of the body's vitamin D stores. It is effective in the treatment of RICKETS and OSTEOMALACIA, both in azotemic and non-azotemic patients. Calcifediol also has mineralizing properties.Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones.Dichloroethylenes: Toxic chlorinated unsaturated hydrocarbons. Include both the 1,1- and 1,2-dichloro isomers. Both isomers are toxic, but 1,1-dichloroethylene is the more potent CNS depressant and hepatotoxin. It is used in the manufacture of thermoplastic polymers.Tretinoin: An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE).Dehydroepiandrosterone: A major C19 steroid produced by the ADRENAL CORTEX. It is also produced in small quantities in the TESTIS and the OVARY. Dehydroepiandrosterone (DHEA) can be converted to TESTOSTERONE; ANDROSTENEDIONE; ESTRADIOL; and ESTRONE. Most of DHEA is sulfated (DEHYDROEPIANDROSTERONE SULFATE) before secretion.Prodrugs: A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.Perhexiline: 2-(2,2-Dicyclohexylethyl)piperidine. Coronary vasodilator used especially for angina of effort. It may cause neuropathy and hepatitis.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Oxymorphone: An opioid analgesic with actions and uses similar to those of MORPHINE, apart from an absence of cough suppressant activity. It is used in the treatment of moderate to severe pain, including pain in obstetrics. It may also be used as an adjunct to anesthesia. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1092)Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Sparteine: A quinolizidine alkaloid isolated from several FABACEAE including LUPINUS; SPARTIUM; and CYTISUS. It has been used as an oxytocic and an anti-arrhythmia agent. It has also been of interest as an indicator of CYP2D6 genotype.Time Factors: Elements of limited time intervals, contributing to particular results or situations.NADP: Nicotinamide adenine dinucleotide phosphate. A coenzyme composed of ribosylnicotinamide 5'-phosphate (NMN) coupled by pyrophosphate linkage to the 5'-phosphate adenosine 2',5'-bisphosphate. It serves as an electron carrier in a number of reactions, being alternately oxidized (NADP+) and reduced (NADPH). (Dorland, 27th ed)Dexamethasone: An anti-inflammatory 9-fluoro-glucocorticoid.Genes, Reporter: Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.Tamoxifen: One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM.Mice, Inbred C57BLPlant Extracts: Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.Chromatography, Liquid: Chromatographic techniques in which the mobile phase is a liquid.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
List of MeSH codes (D12.776)
List of MeSH codes (D08)
... cytochrome p-450 cyp1a1 MeSH D08.244.453.040.777 --- cytochrome p-450 cyp1a2 MeSH D08.244.453.040.888 --- cytochrome p-450 ... cytochrome p-450 cyp2b1 MeSH D08.811.682.690.708.170.040.555 --- cytochrome p-450 cyp2d6 MeSH D08.811.682.690.708.170.040.777 ... cytochrome p-450 cyp1a1 MeSH D08.811.682.690.708.170.040.443 --- cytochrome p-450 cyp1a2 MeSH D08.811.682.690.708.170.040.499 ... cyp2b1 MeSH D08.244.453.040.944 --- cytochrome p-450 cyp2d6 MeSH D08.244.453.040.972 --- cytochrome p-450 cyp2e1 MeSH D08.244. ...
NIOSHTIC-2 Publications Search - 20024194 - Effects of paving asphalt fume exposure on genotoxic and mutagenic activities in...
... we have demonstrated that inhalation exposure of rats to asphalt fumes resulted in dose-dependent induction of CYP1A1 with ... concomitant down-regulation of CYP2B1 and increased phase II enzyme quinone reductase activity in the rat lung. In the ... exposure of rats to asphalt fumes resulted in dose-dependent induction of CYP1A1 with concomitant down-regulation of CYP2B1 and ...
Oxygen-mediated enhancement of primary hepatocyte metabolism, functional polarization, gene expression, and drug clearance |...
... we quantified the activities of CYP1A1/2 and CYP2B1/2 enzymes in both rat and human cells. Fig. 3A compares Cyp1A1/2 and Cyp2B1 ... A) Activity of Cyp1A1/2 and Cyp2B1/2 in oxygenated co-cultures on the first day of culture (day 1) compared to hepatocytes from ... Oxygenated Co-Cultures Support High Levels of Cyp1A1/2 and Cyp2B1/2 Activity.. Oxygen is an important component of the hepatic ... D) Cyp1A1/2 activity in co-cultures of hepatocytes with endothelial cells or 3T3-J2 fibroblasts or those cultured alone (day 1 ...
Age-related changes in the mRNA levels of CYP1A1, CYP2B1/2 and CYP3A1 isoforms in rat small intestine | Genes & Nutrition |...
at 65°C (CYP1A1), 55.8°C (CYP2B1/2) or 62.3°C (CYP3A1) and finally 90 s. at 72°C. The studied mRNAs and standard internal ... Changes in CYP2B1/2 mRNA expression were similar to those observed for CYP1A1, a constitutive mRNA level of this isoform was ... RNA was isolated from intestinal mucosa, and then standard RT-PCR was used for the analysis of CYP1A1, CYP2B1/2 and CYP3A1 mRNA ... 1994). High inducibility of CYP1A1, CYP2B1/2 and CYP3A1 genes in the small intestine of aged rats could also promote ...
In vitro inhibition of CYP2B1 monooxygenase by beta-myrcene and other monoterpenoid compounds
Cytochrome P-450 CYP1A1 / metabolism * Cytochrome P-450 CYP2B1 / antagonists & inhibitors* * Cytochrome P-450 CYP2B1 / ... In vitro inhibition of CYP2B1 monooxygenase by beta-myrcene and other monoterpenoid compounds Toxicol Lett. 1997 Jun 16;92(1): ... a selective marker for CYP2B1, was determined in a pool of liver microsomes prepared from phenobarbital-treated rats. The ...
NIOSHTIC-2 Search Results - Full View
Modulation of cytochrome P450 by 5,5'-bis-trifluoromethyl-2,2'-dichlorobiphenyl, a unique environmental contaminant
Cytochrome P-450 CYP1A1 / metabolism * Cytochrome P-450 CYP1A2 / metabolism * Cytochrome P-450 CYP2B1 / metabolism ... Additionally, CYP2B1 and CYP2B2 proteins and activities were induced following treatment with the high dose of 5,5CF3-2,2PCB ... Furthermore, 5,5CF3-2,2PCB appears to be acting as a mixed-type inducer since phenobarbital-like induction of CYP2B1 and 2B2 ... Specifically, a dose-dependent induction of the cytochrome P450s 1A1 and 1A2 (CYP1A1 and CYP1A2) proteins and their respective ...
Diindolylmethane in Treating Patients Undergoing Surgery for Stage I or Stage II Prostate Cancer - Full Text View -...
NIOSHTIC-2 Publications Search - 20025858 - Effects of exposure to diesel exhaust particles (DEP) on pulmonary metabolic...
... has been shown to induce time-dependent changes in CYP1A1and CYP2B1 in the lung. The present study evaluated the role of these ... but markedly enhanced by CYP1A1 or CYP2B1 supersomes with all the cofactors, suggesting that both CYP1A1 and CYP2B1 were ... The bioactivation of mutagens are metabolic enzyme- and substrate-specific, and both CYP1A1 and CYP2B1 play important roles in ... The mutgenicity of 2-AA, 2-AF, 1-NP, and DEPE were significantly decreased in the presence of inhibitors for CYP1A1 (alpha- ...
NIOSHTIC-2 Search Results - Full View
CYP2B1 levels and enzyme activity were not significantly affected by AFC exposure. In contrast, CYP1A1 levels and activity were ... The activities of CYP2B1 and CYP1A1 were determined by monitoring xenobiotic metabolism of 7-pentoxyresorufin and 7- ... CYP2B1 and CYP1A1 levels were determined by immunochemical analysis. Micronucleus (MN) formation in bone-marrow polychromatic ... These results demonstrate that AFC exposure induced CYP1A1 activity and increased the enzyme levels of CYP1A1 in lung ...
RESULTS: The value of half maximal inhibitory concentration of DHM for CYP1A1/2, CYP1A2, and CYP2B1 were determined to be 4.1, ... The effects of flavonoids on CYP1A1/2, CYP1A2 or CYP2B1/2 enzyme activities in microsomes were measured using marker activities ... CONCLUSIONS: Dihydromyricetin doesnt significantly interfere with metabolic activity of CYP1A1/2 and CYP2B1 enzymes.... ... With the exception of a weak induction of CYP2B1 and CYP1A2 in the middle part of small intestine and in the liver, ...
Molecules | Free Full-Text | Berberine Activates Aryl Hydrocarbon Receptor but Suppresses CYP1A1 Induction through miR-21-3p...
While CYP1A1 mRNA was elevated, berberine-induced miR-21-3p suppressed the increase of functional CYP1A1 protein expression. ... The 24-h exposure to 10 μM berberine did not change CYP1A1 mRNA stability, protein level and function. Berberine significantly ... berberine had the most potent and statistically significant effects on AhR activation and CYP1A1/1A2/1B1 mRNA induction. ... increased micro RNA (miR)-21-3p by 36% and the transfection of an inhibitor of miR-21-3p restored the induction of CYP1A1 ...
Palamanda J[au] - PubMed - NCBI
Evaluation of CYP1A1 and CYP2B1/2 m-RNA induction in rat liver slices using the NanoString technology: a novel tool for drug ... High-throughput evaluation of CYP1A1 and 2B1 induction in rat liver slices using a semi-automated system. ... A high-throughput cell-based reporter gene system for measurement of CYP1A1 induction. ...
Murgolo N[au] - PubMed - NCBI
Effect of the metabolic capacity in rat liver S9 on the positive results of <i>in vitro</i>...
Then, 10 μL (for CYP1A1, CYP1A2, CYP2B1/2, CYP2E1, CYP3A1, CYP3A2 and CYP4A) or 3 μL (for CYP2C6, CYP2C11, and CYP2D1 and NADPH ... 2). 3-MC increased CYP1A1 and CYP1A2 levels and decreased CYP2B1/2 level but did not change CYP2C6, CYP2C11, CYP2D1, CYP2E1, ... PB-BNF increased cytochrome P450 (CYP) activity and CYP1A1, CYP1A2, CYP2B1/2, CYP2C6, CYP3A1, and CYP3A2 expression in rat S9, ... 1). Western blot analysis revealed that protein expression of CYP1A1, CYP1A2, CYP2B1/2, CYP2C6, CYP3A1, and CYP3A2 and NADPH ...
In monkeys, no significant site-selective differences in CYP1A1 and CYP2B1 activities were found. In contrast, CYP2E1 activity ... Induction of rat CYP1A1 activity by β-naphthoflavone (administered ip) was much greater in the airways and lung parenchyma (∼30 ... In rats, CYP1A1 (ethoxyresorufin) and CYP2B (pentoxyresorufin) dealkylase activities were highest in the parenchyma, whereas ...
Antibody concentrations were as follows; 2.5, 5, 10, and 20 μl for anti-CYP2C, 10 and 20 μl for anti-CYP1A1/2, 1 and 5 μl for ... Long-term treatment with nicotine also had no significant effect on rat hepatic CYP2B1 expression (Miksys et al., 2000); ... Nicotine has been shown to increase hepatic and respiratory CYP1A1/2 (Iba et al., 1999), hepatic CYP2E1 (Howard et al., 2001), ... Anti-CYP2D6, anti-CYP3A4, anti-CYP2C, anti-CYP1A1/2, and preimmune serum did not inhibit NCO. Results were similar at 300 μM ...
NanoString Technologies - Wikipedia
CYP2B1 was the most highly expressed gene, about 120,000-fold higher than the calibrator (Fig. 1B). CYP1A1, CYP2E1, CYP4F5, and ... 1A). CYP1A1 and CYP2J3 were also highly expressed, about 1000-fold higher than the calibrator (Fig. 1A). CYP2B1, CYP2B2, ... The lung has the highest constitutive expression of CYP1A1, CYP1B1, CYP2B1, and CYP4F5 genes, and the liver and kidney have the ... In the current study, we showed that CYP1A1, CYP1B1, CYP2B1, CYP2B2, CYP2C11, CYP2E1, CYP2J3, CYP4F4, CYP4F5, and sEH genes are ...
University of Pennsylvania || School of Medicine || Narayan G Avadhani, Ph.D.
Mitochondrial targeting of intact CYP2B1 and CYP2E1 and N-terminal truncated CYP1A1 proteins in Saccharomyces cerevisiae--role ... Knock-in mouse lines expressing either mitochondrial or microsomal CYP1A1: differing responses to dietary benzo[a]pyrene as ... Role of protein kinase C-mediated protein phosphorylation in mitochondrial translocation of mouse CYP1A1, which contains a non- ...
List of MeSH codes (D12.776) - Wikipedia
Hepatocyte CYP2B6 Can Be Expressed in Cell Culture Systems by Exerting Physiological Levels of Shear: Implications for ADME...
CYP1A1 increased 54-fold, CYP1A2 increased 64-fold, CYP2B1 increased 15-fold, and, most importantly for the thesis of this ... showed that CYP2B1/2, the rat homolog of human CYP2B6, is maintained for at least 39 days in hepatocyte spheroids cultured ... CYP2B1/2 activity was measured by generation of pentoxyresorufin-O dealkylase as pmol per total protein in the culture. Adapted ...
Dealkylation | definition of Dealkylation by Medical dictionary
Turmeric, Curcumin (Curcuma longa) | Plant Profiler | China-Mainland | Sigma-Aldrich
Hepatic cytochrome P-450 (CYP) 1A1, 51 and 53kDa proteins and constitutive CYP1A2 (3.8-fold) and 2B2 (4.0-fold), but not CYP2B1 ... The combination of PhIP and ANIT markedly decreased three liver CYP1A proteins except CYP1A1 and CYP2B2, and the liver S9 from ... In contrast, gavage of curcumin decreased the constitutively detected CYP2B1 and 2E1 in the esophagus, and a single dose of 270 ... a decrease in metabolic activation of PhIP by hepatic CYP1A2 and an increase in the detoxification by UDPGT but not by CYP1A1. ...
Glutathione-S-transferase P protects against endothelial dysfunction induced by exposure to tobacco smoke | Heart and...
CS induced hepatic CYP1A1 expression in WT mice. D: catalytic activity of GST in the mouse lung. Total GST and GSTP activities ... 3C). No changes in the protein expression of other aldehyde-metabolizing enzymes, including ALDH3A1, GSTP, CYP2B1, or CYP2E1, ... C: basal hepatic expression of cytochrome P-450 (CYP)1A1/1A2 was greater in GSTP-null mice compared with WT mice. ... 3B). Hepatic microsomal CYP1A1 expression was significantly increased in tobacco smoke-exposed WT mice (Fig. 3C); however, ...
eLCOSH : Asphalt in Construction: An Interdisciplinary Annotated Bibliography
- Specifically, a dose-dependent induction of the cytochrome P450s 1A1 and 1A2 (CYP1A1 and CYP1A2) proteins and their respective activities was observed, with significant induction occurring in both the low and high dose CF3-PCB groups, compared to control. (nih.gov)
- PB-BNF increased cytochrome P450 (CYP) activity and CYP1A1, CYP1A2, CYP2B1/2, CYP2C6, CYP3A1, and CYP3A2 expression in rat S9, whereas it decreased CYP2C11 and CYP2E1 expression. (go.jp)
- PB-BNF-induced S9 enhanced the micronucleus induction (MI) of benzo[ a ]pyrene (BaP), cyclophosphamide (CPA), and 2-amino-1-methyl-6-phenylimidazo[4,5- b ]pyridine hydrochloride (PhIP), which are metabolized by CYP1A1, CYP2C6, and CYP1A2, respectively. (go.jp)
- 5. Cytochrome P450 (CYP1A1, CYP1A2, CYP2B1/2) activities of human hepatocyte/spheroids, which were main enzymes of drug metabolism, were 2.5〜3 times higher than those of usual monolayer culture. (nii.ac.jp)
- The widespread belief is that higherdose radiation increased the expression of CYP1A1 and CYP1B1 of rat, zebrafish or human, CYP1A2, CYP2B1, and CYP3A1 of rat, and CYP2E1 of mouse or rat, and decreased that of rat's CYP2C11 and CYP2D1. (eurekaselect.com)
- There is a battery of genes affected in this manner and targets include certain xenobiotic-metabolizing enzymes, such as CYP1A1,CYP1A2, CYP2B1, and UGT1A6. (indigobiosciences.com)
- In addition, P-450HFLb also cross-reacted with both monospecific antibodies to rat CYP1A1 and CYP1A2. (meta.org)
- In rats in vivo myristicin induced CYP1A1 , CYP1A2 , CYP2B1 , CYP2B2 , and CYP2E1 . (wikidot.com)
- In rats, CYP1A1 (ethoxyresorufin) and CYP2B (pentoxyresorufin) dealkylase activities were highest in the parenchyma, whereas CYP2E1 ( p -nitrophenol) hydroxylase activity was highest in the airways. (aspetjournals.org)
- In addition, there was a significant induction of CYP1A1, CYP1B1, CYP4A3, and soluble epoxide hydrolase and a significant inhibition of CYP2C11 and CYP2E1 in the hypertrophied hearts as compared with the control. (aspetjournals.org)
- CYP1A1, CYP2E1, and CYP4A3 gene expression was induced in the kidney, and CYP4A3 was induced in the liver of isoproterenol-treated rats. (aspetjournals.org)
- that xenobiotic-inducible CYPs such as rat CYP 1A1 , CYP2E1 and CYP2B1, and mouse CYP 1A1 , contain chimeric noncanonical -targeting signals that are capable of targeting proteins to both the ER and. (123doc.org)
- Pulmonary bioactivation of trichloroethylene to chloral hydrate: relative contributions of CYP2E1, CYP2F, and CYP2B1. (kegg.jp)
- RNA was isolated from intestinal mucosa, and then standard RT-PCR was used for the analysis of CYP1A1, CYP2B1/2 and CYP3A1 mRNA expression. (biomedcentral.com)
- The rat CYP expression is rather constant between the different individuals, and the main rat intestinal forms are CYP1A1, CYP2C, CYP2D6 and CYP3A1. (diva-portal.org)
- In the determination of CYP1 function, 7-ethoxyresorufin is generally used as a common substrate of CYP1s, and CYP1A1 has the highest turnover rate in 7-ethoxyresorufin O -deethylation (EROD) [ 2 ]. (mdpi.com)
- There was a significant inverse correlation between Factor VII levels and induction of hepatic ethoxyresorufin O-deethylating (EROD) activity, reflecting CYP1A1, and total P450 content. (mysciencework.com)
- Microsomal protein level, NADPH cytochrome c reductase activity, and the activities and protein levels of cytochrome P-450 isozymes CYP1A1 and CYP2B1 were monitored to assess the effects of AFC exposure on pulmonary P-450. (cdc.gov)
- The basic mechanism of action of dioxin and related compounds has been extensively studied, in particular as it relates to regulation of cytochrome P450 1A1 (CYP1A1). (indigobiosciences.com)
- Previously, we have demonstrated that inhalation exposure of rats to asphalt fumes resulted in dose-dependent induction of CYP1A1 with concomitant down-regulation of CYP2B1 and increased phase II enzyme quinone reductase activity in the rat lung. (cdc.gov)
- Furthermore, 5,5'CF3-2,2'PCB appears to be acting as a mixed-type inducer since phenobarbital-like induction of CYP2B1 and 2B2 was also associated with exposure. (nih.gov)
- Among protoberberines at non-cytotoxic concentrations (≤10 μM), berberine had the most potent and statistically significant effects on AhR activation and CYP1A1/1A2/1B1 mRNA induction. (mdpi.com)
- Berberine significantly increased micro RNA (miR)-21-3p by 36% and the transfection of an inhibitor of miR-21-3p restored the induction of CYP1A1 protein with a 50% increase. (mdpi.com)
- Induction of rat CYP1A1 activity by β-naphthoflavone (administered ip) was much greater in the airways and lung parenchyma (∼30-fold) than in the liver (∼10-fold) or trachea (∼2.5-fold). (aspetjournals.org)
- Inducibility of CYP1A1 gene was evident in intestinal mucosa at 2-, 4- and 20-month-old rats. (biomedcentral.com)
- The effects of MYR and other monoterpenes on the activity of pentoxyresorufin-O-depenthylase (PROD), a selective marker for CYP2B1, was determined in a pool of liver microsomes prepared from phenobarbital-treated rats. (nih.gov)
- Exposure of rats to diesel exhaust particles (DEP) or carbon black (CB) has been shown to induce time-dependent changes in CYP1A1and CYP2B1 in the lung. (cdc.gov)
- Oxidation reactions mediated by CYP2C6 (in control rat liver) and CYP2B1 (in microsomes from phenobarbital-induced rats) were very sensitive to inhibition, but not inactivation, by parathion. (aspetjournals.org)
- The mutgenicity of 2-AA, 2-AF, 1-NP, and DEPE were significantly decreased in the presence of inhibitors for CYP1A1 (alpha-naphthoflavone) or CYP2B (metyrapone), but markedly enhanced by CYP1A1 or CYP2B1 supersomes with all the cofactors, suggesting that both CYP1A1 and CYP2B1 were responsible for mutagen activation. (cdc.gov)
- Antibodies to phenobarbital-inducible rat CYP2B1 or to scup P450B, a purative CYP2B, detected one or more proteins in several species, suggesting that CYP2B-like proteins are highly expressed in some tropical fishes. (elsevier.com)
- The constitutive intestinal CYP1A1 mRNA expression changes during maturation and aging. (biomedcentral.com)
- We found that the mRNA expression of 1A1 was absent in the liver and that the CYP2B1, CYP2Cs, CYP2D1 and Pgp all had a stronger mRNA expression in the small intestine compared to the liver. (diva-portal.org)
- While CYP1A1 mRNA was elevated, berberine-induced miR-21-3p suppressed the increase of functional CYP1A1 protein expression. (mdpi.com)
- LTr-1 activated both binding of the aryl hydrocarbon (Ah) receptor to its cognate DNA responsive element and expression of the Ah receptor-responsive gene CYP1A1. (lifeextensionvitamins.com)