p450 isozymes benzoapyrene: Topics by WorldWideScience.org

[mRNA level and cytochrome P450 1A activity in the liver of C57BL mice induced by various xenobiotics].

An assay for the microsomal hydroxylation of lauric acid (LA), based on HPLC with flow-through radiochemical detection, has been developed. Conditions were optimized for resolution and quantitation of three microsomal metabolites of "1"4C-LA, one of which has not been reported previously as a metabolite of LA in mammalian microsomal incubations. These products, 12-(omega)-hydroxy-LA, 11-(omega-1)-hydroxy-LA, and a novel metabolite, 10-(omega-2)-hydroxy-LA, were isolated by HPLC and identified by gas chromatography/mass spectrometry. In the presence of NADPH, the formation of all three metabolites was linear with time and microsomal protein concentration. Hydrogen peroxide also supported the microsomal metabolism of LA, although the ratio of metabolites was substantially different than that produced by NADPH-supported microsomes. Several biochemical probes (metyrapone, #alpha#-naphthoflavone, 2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride, and 10-undecynoic acid) were used to ...

Synthesis, characterization and biologic effects of polybrominated naphthalenes

The rate of hepatic cytochrome P450 Cypla1 and Cyp1a2 induction was investigated in C57BL male mice during induction with o-aminoazotoluene (OAT), benzo[a]pyrene (BP) and 1,4-dihydroxyanthraquinone (AQ). The Cypla1 mPNA level determined by quantitative RT-competitive PCR increased more than three orders of magnitude during induction with OAT and BP compared with untreated animals and remained unchanged during induction with AQ. The Cypla2 mRNA level was only 8.5, 18.7 and 1.9 times higher during induction with OAT, BP and AQ respectively than in untreated mice. At the same time 7-Ethoxyresorufin-O-deethylase (EROD) and 7-Methoxyresorufin-O-demethylase (MROD) activities of Cypla were also investigated in liver. The increase of Cypla1 mRNA level correlated with the increase of EROD activity. This suggests involvement of the transcriptional mechanism of the inducibility of this enzyme. In the case of Cypla2 there was ...

A cytochrome P450 terpenoid hydroxylase linked to the suppression of insect juvenile hormone synthesis

Although polybrominated naphthalenes (PBNs) are contaminants of the commercial fire retardant fireMaster BP-6, the individual PBN isomers have not been identified. In order to study PBNs possessing an analogous level of bromination to those found in fireMaster BP-6, three synthetic PBN mixtures, averaging 5.0, 5.3, and 5.6 bromines per naphthalene were synthetized and partially characterized. The PBN mixtures were administered to immature male Wistar rats and found to be potent inducers of cytochrome P-450-dependent monooxygenases. At the lowest dose tested, 30 mumol X kg-1, each PBN mixture caused maximal induction of benzo(a)pyrene hydroxylase activity. On the basis of enzyme activities, ligand-binding spectra and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the PBN mixtures were determined to be 3-methylcholanthrene-type inducers of cytochrome P-450 (P-448), ...

1984-07-01

Induction of Hepatic Microsomal Cytochrome P450 by N,N-dimethylformamide in Sprague-Dawley Rats

A cDNA encoding a cytochrome P450 enzyme was isolated from a cDNA library of the corpora allata (CA) from reproductively active Diploptera punctata cockroaches. This P450 from the endocrine...Full Text Available

1998-10-27

KoreaScience (Korea)

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1999-03-01

Clofibrate-induced cytochrome P450-lauric acid omega hydroxylase(P450LA omega):purification, cDNA cloning, sequence and regulation

Isozymes of the Glycolytic Enzymes in Endosperm from Developing Castor Oil Seeds ¹

A cytochrome P450 that hydroxylates lauric acid at the 12 position (P450LA omega) was isolated from liver microsomes of clofibrate treated rats. P450LA omega was immunologically distinct from P450s a,b,c,d,e,f,g,h,j,PB1, and PCN1. Polyclonal antibody against P450LA omega was utilized to screen a gt11 cDNA library. A clone (pP450LA omega), was isolated and its sequence determined. The P450LA omega mRNA is a minimum 2387 nts in length and codes for a P450 of Mr.58,222 daltons. This protein shares less than 35% amino acid similarity with P450s b,c,d,e,f,PB1, and PCN1; however, it does contain a hydrophobic amino ...

1986-05-01

Evaluation of Acyl Coenzyme A Oxidase (Aox) Isozyme Function in the n-Alkane-Assimilating Yeast Yarrowia lipolytica

Ion filtration chromatography on diethylaminoethyl-Sephadex A-25 has been used to separate two isozymes each of triose phosphate isomerase, glyceraldehyde 3-phosphate dehydrogenase, glycerate 3-phosphate...Full Text Available

1982-04-01

On the General Mechanism of Selective Induction of Cytochrome P450 Enzymes by Chemicals: Some Theoretical Considerations

We have identified five acyl coenzyme A (CoA) oxidase isozymes (Aox1 through Aox5) in the n-alkane-assimilating yeast Yarrowia lipolytica, encoded by the POX1...Full Text Available

1999-09-01

Clinical outcomes and management of mechanism-based inhibition of cytochrome P450 3A4

Importance of the fieldThe cytochrome P450 (CYP) isoforms that are selectively induced following exposure to structurally-diverse chemicals often are the ones capable...Full Text Available

2010-04-01

Covalent Modification of Thr302 in Cytochrome P450 2B1 by the Mechanism-Based Inactivator 4-tert-Butylphenylacetylene

Mechanism-based inhibition of cytochrome P450 (CYP) 3A4 is characterized by NADPH-, time-, and concentration-dependent enzyme inactivation, occurring when some drugs are converted by CYPs to reactive...Full Text Available

2005-03-01

Transposable elements are enriched within or in close proximity to xenobiotic-metabolizing cytochrome P450 genes

The mechanism of inactivation of cytochrome P450 2B1 (CYP2B1) by 4-tert-butylphenylacetylene (BPA) has been characterized previously to be caused by the covalent binding of a reactive...Full Text Available

2010-06-01

Soluble Epoxide Hydrolase Inhibition: Targeting Multiple Mechanisms of Ischemic Brain Injury with a Single Agent

BackgroundTransposons, i.e. transposable elements (TEs), are the major internal spontaneous mutation agents for the variability of eukaryotic genomes. To address the general issue...Full Text Available

Protection against chemical-induced lung injury by inhibition of pulmonary cytochrome P-450.

SummarySoluble epoxide hydrolase (sEH) is a key enzyme in the metabolic conversion and degradation of P450 eicosanoids called epoxyeicosatrienoic acids (EETs). Genetic variations...Full Text Available

2009-03-01

Molecular basis of the inhibition of human aromatase (estrogen synthetase) by flavone and isoflavone phytoestrogens: A site-directed mutagenesis study.

Protection afforded by trialkyl phosphorothionates against the lung injury caused by trialkyl phosphorothiolates probably results from the inhibition by the P = S moiety of the thionates, of one or...Full Text Available

1990-04-01

Induction of cytochrome P450 1A by cow milk-based formula: a comparative study between human milk and formula

Flavone and isoflavone phytoestrogens are plant chemicals and are known to be competitive inhibitors of cytochrome P450 aromatase with respect to the androgen substrate. Aromatase is the enzyme that...Full Text Available

1998-02-01

Evolutionary history of a specialized P450 propane monooxygenase

During the treatment of neonatal apnea, formula-fed infants, compared to breastfed infants, show nearly three-fold increase in clearance of caffeine, a substrate...Full Text Available

2005-09-01

Metabolism of benzo(a)pyrene by isolated perfused testis and testicular homogenate

SummaryThe evolutionary pressures that shaped the specificity and catalytic efficiency of enzymes can only be speculated. While directed evolution experiments show that new functions...Full Text Available

2008-11-28

Mutations induced in the hypoxanthine phosphoribosyl transferase gene by three urban air pollutants: acetaldehyde, benzo[a]pyrene diolepoxide, and ethylene oxide.

In an effort to improve the extrapolation of laboratory data to man and estimate risk of human reproductive toxicity associated with environmental exposure, the pharmacokinetic parameters of the testicular compartment are being studied. Of particular interest is the variety of enzyme systems capable of activating and detoxicating environmental chemicals and drugs. This report compares the metabolism of benzo(a)pyrene by the isolated perfused testis and testicular homogenates in vitro. The cell free in vitro system metabolized benzo(a)pyrene at a much greater rate than the perfused testis and produced a different spectrum of metabolites. Reliable laboratory prediction of biotransformation by the whole organ or intact animal is an essential aspect of reproductive toxicology.

1980-12-01

Preferential induction of cytochrome P450 1A1 over cytochrome P450 1B1 in human breast epithelial cells following exposure to quercetin

Provisional mutational spectra at the hypoxanthine phosphoribosyl transferase (HPRT) locus in vitro have been worked out for acetaldehyde (AA) and benzo[a]pyrene diolepoxide (BPDE) in human (T)-lymphocytes...Full Text Available

1994-10-01

British Library Electronic Table of Contents (United Kingdom)

Estrogen metabolism is suggested to play an important role in estrogen-induced breast carcinogenesis. Epidemiologic studies suggest that diets rich in phytoestrogens are associated with a reduced risk of breast cancer. Phytoestrogens are biologically active plant compounds that structurally mimic 17b-estradiol (E2). We hypothesize that phytoestrogens, may provide protection against breast carcinogenesis by altering the expression of estrogen-metabolizing enzymes cytochrome P450 1A1 (Cyp1A1) and 1B1 (Cyp1B1). Cyp1A1 and Cyp1B1 are responsible for the metabolism of E2 to generate 2-hydroxyestradiol (2-OHE2) and 4-hydroxyestradiol (4-OHE2), respectively. Studies suggest that 2-OHE2 and 2-methoxyestradiol may protect against breast carcinogenesis, while 4-OHE2 is carcinogenic in rodent models....

2008-01-01

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Myocardial pharmacokinetics of ebastine, a substrate for cytochrome P450 2J, in rat isolated heart

British Library Electronic Table of Contents (United Kingdom)

BACKGROUND AND PURPOSE It is well established that cytochrome P450 2J (CYP2J) enzymes are expressed preferentially in the heart, and that ebastine is a substrate for CYP2J, but it is not known whether ebastine is metabolized in myocardium. Therefore, we investigated its pharmacokinetics in the rat isolated perfused heart. EXPERIMENTAL APPROACH Rat isolated hearts were perfused in the recirculating mode with ebastine for 130-min. The concentrations of ebastine and its metabolites, hydroxyebastine and carebastine, were measured using liquid chromatography with a tandem mass spectrometry. The data were analysed by a compartmental model. The time course of negative inotropic response was linked to ebastine concentration to determine the concentration-effect relationship. KEY RESULTS Ebastine w...

2011-01-01

Murphy Oil Spill | Response to 2005 Hurricanes | US EPA

Intravenous Formulation of HET0016 for Inhibition of Rat Brain 20-Hydroxyeicosatetraenoic Acid (20-HETE) Formation

Aromatic Hydrocarbons (PAHs) PAHs, such as benzo(a)pyrene, are commonly found in fuel oils and crude oil, and were detected above LDEQ screening levels for residential soil in...

2008-03-24

Cyp1b1 exerts opposing effects on intestinal tumorigenesis via exogenous and endogenous substrates

N-Hydroxy-N′-(4-n-butyl-2-methylphenyl)formamidine (HET0016) is a potent inhibitor of 20-hydroxyeicosatetraenoic acid (20-HETE) formation by specific cytochrome P450 (CYP) isoforms....Full Text Available

2008-11-01

Endogenous biosynthesis of arachidonic acid epoxides in humans: Increased formation in pregnancy-induced hypertension

Cytochrome P450 1B1 (Cyp1b1) metabolism contributes to physiological functions during embryogenesis, but also to carcinogenic activation of polycyclic aromatic hydrocarbons (PAH). We generated...Full Text Available

2008-09-15

ATF4 and the integrated stress response are induced by ethanol and cytochrome P450 2E1 in human hepatocytes

Arachidonic acid is metabolized by means of P450 isoenzyme(s) to form epoxyeicosatrienoic acids (EETs) and their corresponding dihydroxy derivatives (DHETs). In the present study, we established the presence in human urine of 8,9-, 11,12-, and 14,15-EETs and their corresponding DHETs by developing quantitative assays and using negative ion, chemical ionization GC/MS and octadeuterated internal standards. Urinary excretion of 8,9- and 11,12-DHET increased in healthy pregnant women compared with nonpregnant female volunteers. By contrast, excretion of 11,12-DHET and 14,15-DHET, but not the 8,9-DHET regioisomer, increased even further in patients with pregnancy-induced hypertension. Intravenous administration of (3H)14,15-EET to three dogs markedly increased its DHET in plasma. The terminal half-life ranged from 7.9-12.3 min and the volume of distribution (3.5-5.3 liters) suggested limited distribution outside the plasma compartment. Negligible ...

1990-08-01

British Library Electronic Table of Contents (United Kingdom)

Background & AimsMolecular mechanisms underlying alcoholic liver disease (ALD) are still not fully understood. Activating transcription factor-4 (ATF4) is the master coordinator of the integrated stress response (ISR), an adaptive pathway triggered by multiple stressors. which can promote cell death and induce metabolic dysregulation if the stress is intense or prolonged. The aim of this study was to assess the effect of alcohol on the ISR signaling pathway in human liver cells and to define the role of cytochrome P450 2E1 (CYP2E1) in this response. MethodsPrimary cultured human hepatocytes and human HepG2 cells over-expressing CYP2E1 by adenoviral infection were exposed to ethanol (25-100mM) for 8-48h. ResultsEthanol treatment of both liver cells up-regulated ATF4 as well as the pro-survi...

2011-01-01

Comparative Evaluation of Different Cell Lysis and Extraction Methods for Studying Benzo(a)pyrene Metabolism in HT-29 Colon Cancer Cell Cultures

British Library Electronic Table of Contents (United Kingdom)

Abstract Lysis and extraction of cells are essential sample processing steps for investigations pertaining to metabolism of xenobiotics in cell culture studies. Of particular importance to these procedures are maintaining high lysis efficiency and analyte integrity as they influence the qualitative and quantitative distribution of drug and toxicant metabolites in the intra- and extracellular milieus. In this study we have compared the efficiency of different procedures viz. homogenization, sonication, bead beating, and molecular grinding resin treatment for disruption of HT-29 colon cells exposed to benzo(a)pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH) compound and a suspected colon carcinogen. Also, we have evaluated the efficiency of various procedures for extracting BaP parent c...

2011-01-01

Benzo[a]pyrene diol epoxide-DNA cis adduct formation through a trans?chlorohydrin?intermediate

One-electron reduction of chloroperoxidase by radiolytically generated electrons

Alkylation of DNA by 7r,8t-dihydroxy,9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) forms mainly trans adducts (with respect to the C-9/10...Full Text Available

1997-03-04

One-electron reduction of chloroperoxidase by radiolytically generated electrons

Upon irradiation of aqueous ethylene glycol/water solutions of native chloroperoxidase (CPO) with {sup 60}Co-gamma rays at 77K one observes the one-electron reduction of the enzyme active site by radiolytically generated thermolyzed electrons. In the present study the first absorption spectrum of a low-spin ferrous form of CPO is reported which has peaks at 438, 532 and 563 nm, similar to those observed previously for cytochrome P-450. All previously described ferrous forms of CPO are high spin. In order to observe the final results of the CPO reaction with electrons, the spectral changes of native enzyme after room temperature-gamma-irradiation have also been investigated. Evidence of changes is also presented probably connected with disruption of the tertiary structure of enzyme, correlated with decrease of enzyme activity.

1990-05-16

Antioxidant properties of 4-methylcoumarins in in vitro cell-free systems

Upon irradiation of aqueous ethylene glycol/water solutions of native chloroperoxidase (CPO) with "6"0Co-gamma rays at 77K one observes the one-electron reduction of the enzyme active site by radiolytically generated thermolyzed electrons. In the present study the first absorption spectrum of a low-spin ferrous form of CPO is reported which has peaks at 438, 532 and 563 nm, similar to those observed previously for cytochrome P-450. All previously described ferrous forms of CPO are high spin. In order to observe the final results of the CPO reaction with electrons, the spectral changes of native enzyme after room temperature-gamma-irradiation have also been investigated. Evidence of changes is also presented probably connected with disruption of the tertiary structure of enzyme, correlated with decrease of enzyme activity.

1990-05-01

British Library Electronic Table of Contents (United Kingdom)

4-Methylcoumarins that possess two hydroxyl groups ortho to each other in the benzenoid ring have shown to have excellent antioxidant and radical-scavenging properties in different experimental models. Furthermore, they cannot be metabolized by the liver P450 monoxygenases and thus cannot form 3,4-coumarin epoxides, which are believed to be mutagenic. Herein, we present a study on the structure activity relationship of eight synthetic 4-methylcoumarins, carried out by employing a series of different chemical cell-free tests. These compounds were tested by means of three assays involving one redox reaction with the oxidant (DPPH assay, ABTS+ assay and FRAP). Other assays were employed to evaluate the antioxidant properties of the coumarins under investigation against NO, O2- and HClO, which...

2010-01-01

Erratum to: Inhibition of triclabendazole metabolism in vitro by ketoconazole increases disruption to the tegument of a triclabendazole-resistant isolate of Fasciola hepatica

British Library Electronic Table of Contents (United Kingdom)

A study has been carried out to investigate whether the action of triclabendazole (TCBZ) against Fasciola hepatica is altered by inhibition of drug metabolism. The cytochrome P450 (CYP 450) enzyme pathway was inhibited using ketoconazole (KTZ) to see whether a TCBZ-resistant isolate could be made more sensitive to TCBZ action. The Oberon TCBZ-resistant and Cullompton TCBZ-susceptible isolates were used for these experiments. The CYP 450 system was inhibited by a 2-h pre-incubation in ketoconazole (40??M), then incubated for a further 22?h in NCTC medium containing either KTZ, KTZ?+?nicotinamide adenine dinucleotide phosphate (NADPH) (1?nM), KTZ?+?NADPH?+?TCBZ (15??g/ml), or KTZ?+?NADPH?+?triclabendazole sulphoxide (TCBZ.SO; 15??g/ml). Changes to fluke ultrastructure following drug treatmen...

2011-01-01

Cotton plants expressing CYP6AE14 double-stranded RNA show enhanced resistance to bollworms

British Library Electronic Table of Contents (United Kingdom)

RNA interference (RNAi) plays an important role in regulating gene expression in eukaryotes. Previously, we generated Arabidopsis and tobacco plants expressing double-stranded RNA (dsRNA) targeting a cotton bollworm (Helicoverpa armigera) P450 gene, CYP6AE14. Bollworms fed on transgenic dsCYP6AE14 plants showed suppressed CYP6AE14 expression and reduced growth on gossypol-containing diet (Mao et?al., in Nat Biotechnol 25: 1307?1313, 2007). Here we report generation and analysis of dsRNA-expressing cotton (Gossypium hirsutum) plants. Bollworm larvae reared on T2 plants of the ds6-3 line exhibited drastically retarded growth, and the transgenic plants were less damaged by bollworms than the control. Quantitative reverse-transcription polymerase chain reaction (RT-PCR) showed that the CYP6AE1...

2011-01-01

Continuous human cell lines and method of making same

Cell-mediated mutagenesis and cell transformation of mammalian cells by chemical carcinogens. [Rats, hamsters

Substantially genetically stable continuous human cell lines derived from normal human mammary epithelial cells (HMEC) and processes for making and using the same. In a preferred embodiment, the cell lines are derived by treating normal human mammary epithelial tissue with a chemical carcinogen such as benzo(a)pyrene. The novel cell lines serve as useful substrates for elucidating the potential effects of a number of toxins, carcinogens and mutagens as well as of the addition of exogenous genetic material. The autogenic parent cells from which the cell lines are derived serve as convenient control samples for testing. The cell lines are not neoplastically transformed, although they have acquired several properties which distinguish them from their normal progenitors. 2 tabs.

1985-07-01

Air quality monitoring report for Alberta, 1991

We have developed a cell-mediated mutagenesis assay in which cells with the appropriate markers for mutagenesis are co-cultivated with either lethally irradiated rodent embryonic cells that can metabolize carcinogenic hydrocarbons or with primary rat liver cells that can metabolize chemicals carcinogenic to the liver. During co-cultivation, the reactive metabolites of the procarcinogen appear to be transmitted to the mutable cells and induce mutations in them. Assays of this type make it possible to demonstrate a relationship between carcinogenic potency of the chemicals and their ability to induce mutations in mammalian cells. In addition, by simultaneously comparing the frequencies of transformation and mutation induced in normal diploid hamster cells by benzo(a)pyrene (BP) and one of its metabolites, it is possible to estimate the genetic target size for cell transformation in vitro.

1977-01-01

Analysis of EPA`s cost-effectiveness study for the coastal oil and gas effluent limitations guidelines

In 1991, the air quality monitoring program in Alberta consisted of continuous, intermittent, static, portable, mobile, and acid precipitation monitoring networks. The air quality monitoring networks are described and results from the continuous, intermittent, static, and acid precipitation networks are summarized. Regulations and guidelines for individual pollutants are discussed in detail. Pollutants monitored continuously (1-h average basis) include ammonia, CO, coefficient of haze, H{sub 2}S, nitrogen oxides, ozone, SO{sub 2}, and total hydrocarbons. Good air quality was observed most of the time at all continuous monitoring stations in 1991. The frequency of good air quality ratings ranged from 81% at the Edmonton northwest station to 98% at the Fort McMurray station. Intermittent monitoring (every 6th day) was conducted for total suspended particulates and for vinyl chloride monomers in the Fort Saskatchewan area. Chemical analyses of benzo(a)pyrene and lead ...

1993-08-01

Zonal differences in DNA synthesis activity and cytochrome P450 gene expression in livers of male F344 rats treated with five nongenotoxic carcinogens

The US Environmental Protection Agency (EPA) conducted a cost-effectiveness (CE) analysis to estimate the incremental cost of complying with the proposed effluent limitation guidelines (ELGs) for the coastal oil and gas industry (EPA 1995a). EPA`s CE analysis calculates the pounds of each pollutant that would be removed if the chosen discharge option is selected. In 1993, EPA issued final ELGs for the offshore oil and gas industry and published an offshore CE analysis. The chemical characteristics of produced water from the offshore region are essentially the same as those of produced water from the coastal region. It was surprising, therefore, that EPA chose a much longer list of pollutants and generally stricter weighting factors for the coastal CE analysis. This report reviews the data, assumptions, and analyses used in EPA`s coastal CE analysis and identifies alternate data, assumptions, and analyses that could lead to significantly different cost-effectiveness conclusions. Two ...

1995-05-01

Toxicity of ultraviolet-irradiated halothane in mice

Both increased cell proliferation and {open_quotes}altered{close_quotes}CYP gene expression are prominent phenomena associated with liver tumor promotion by nongenotoxic carcinogen treatment. BRDU-labeled parenchymal nuclei were observed primarily in the periportal area of groups of rats, independent of nongenotoxic carcinogen treatment. Treatment with each of the 5 nongenotoxic carcinogens resulted in profound alterations in CPY gene expression at both the transcriptional and translational levels. Expression of CYP1A1, 1A1/2, 3A1, 2B1/2, and 4A immunoproteins demonstrated nongenotoxic carcinogen-specific patterns in both magnitude and zonal distribution. In agreement with the CYP immunoprotein data, treatment with each of the five nongenotoxic carcinogens resulted in a unique composition of mRNAs of CYP2B1, 2B2, 2C6, 2C11, 3A1, 3A2, and 4A1, which were variably increased or decreased relative to the untreated control livers, depending on the treatment. Similarly, the rate and pattern ...

1995-12-31

The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes

One such agent is the widely used anesthetic, halothane. To study the toxicity of u.v. decomposed halothane, mice were exposed to anesthetic concentrations (1.3%) of non- and u.v.-irradiated halothane in oxygen for 90 min. Halothane sleeping times increased from 14.3 min to 72.5 min. Microsomal mixed function oxidase activity decreased, as shown by prolonged pentobarbital sleeping times 1 day after exposure to halothane and irradiated halothane (54.6 min and 149.1 min, respectively, as compared to a 34.6-min control). Quantitative and qualitative differences were found in the amount of (/sup 14/C)-pentobarbital metabolites excreted by u.v. irradiated halothane-exposed mice compared to either oxygen or non-irradiated halothane-exposed groups. In addition, serum glutamic-oxalacetic transaminase (SGOT) of irradiated halothane-exposed mice increased to 233% of the control values, and serum glutamic-pyruvic transaminase (SGPT) were 377% of control values. No significant changes in SGOT or ...

1982-01-01

The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes

Three cDNAs, designated IIA3, IIA3v, and IIA4, coding for P450s in the CYP2A gene subfamily were isolated from a {lambda}gt11 library prepared from human hepatic mRNA. Only three nucleotide differences and a single amino acid difference, Leu{sup 160}{yields}His, were found between IIA3 and IIA3v, indicating that they are probably allelic variants. IIA4 displayed 94% amino acid similarity with IIA3 and IIA3v. The three cDNAs were inserted into vaccinia virus, and recombinant viruses were used to infect human hepatoma Hep G2 cells. Only IIA3 was able to produce an enzyme that had a reduced CO-bound spectrum with a {lambda}{sub max} at 450 nm. This expressed enzyme was able to carry out coumarin 7-hydroxylation and ethoxycoumarin O-deethylation. cDNA-expressed IIA3v and IIA4 failed to incorporate heme and were enzymatically inactive. Analysis of IIA proteins in human liver microsomes, using antibody against rat IIA2, revealed two proteins of 49 ...

1990-02-06

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Systemic responses to inhaled ozone in mice: cachexia and down-regulation of liver xenobiotic metabolizing genes

Three cDNAs, designated IIA3, IIA3v, and IIA4, coding for P450s in the CYP2A gene subfamily were isolated from a #lambda#gt11 library prepared from human hepatic mRNA. Only three nucleotide differences and a single amino acid difference, Leu"1"6"0#->#His, were found between IIA3 and IIA3v, indicating that they are probably allelic variants. IIA4 displayed 94% amino acid similarity with IIA3 and IIA3v. The three cDNAs were inserted into vaccinia virus, and recombinant viruses were used to infect human hepatoma Hep G2 cells. Only IIA3 was able to produce an enzyme that had a reduced CO-bound spectrum with a #lambda#_m_a_x at 450 nm. This expressed enzyme was able to carry out coumarin 7-hydroxylation and ethoxycoumarin O-deethylation. cDNA-expressed IIA3v and IIA4 failed to incorporate heme and were enzymatically inactive. Analysis of IIA proteins in human liver microsomes, using antibody against rat IIA2, revealed two proteins of 49 and 50 ...

1990-02-01

Induction of biotransformation in the liver of Eel (Anguilla anguilla L. ) by sublethal exposure to dinitro-o-cresol: An ultrastructural and biochemical study

Rats or mice acutely exposed to high concentrations of ozone show an immediate and significant weight loss, even when allowed free access to food and water. The mechanisms underlying this systemic response to ozone have not been previously elucidated. We have applied the technique of global gene expression analysis to the livers of C57BL mice acutely exposed to ozone. Mice lost up to 14% of their original body weight, with a 42% decrease in total food consumption. We previously had found significant up-regulation of genes encoding proliferative enzymes, proteins related to acute phase reactions and cytoskeletal functions, and other biomarkers of a cachexia-like inflammatory state in lungs of mice exposed to ozone. These results are consistent with a general up-regulation of different gene families responsive to NF-#kappa#B in the lungs of the exposed mice. In the present study, we observed significant down-regulation of different families of mRNAs in the livers of the exposed mice, ...

2005-10-15

Gene expression profiles deciphering rice phenotypic variation between Nipponbare (Japonica) and 93-11 (Indica) during oxidative stress.

Structural and functional alterations in hepatocytes of the European eel, Anguilla anguilla, following a 4-week-exposure to 5, 50, and 250 micrograms/liter dinitro-o-cresol (DNOC) were investigated by means of electron microscopy and biochemistry and compared to liver pathology in eels exposed to the chemical spill into the Rhine river at Basle in November 1986. Whereas phenological parameters (growth, condition factor) are unaffected, ultrastructural and biochemical alterations are detectable at greater than or equal to 50 and 5 micrograms/liter DNOC, respectively. Structural modifications include: rounding-up of the nuclei; fractionation and reduction of the rough endoplasmic reticulum; proliferation of the smooth endoplasmic reticulum (SER), mitochondria, peroxisomes, and lysosomes; bundles of rod-shaped SER profiles; annulate lamellae; membrane whorls within mitochondria; crystallization of the peroxisomal matrix and glycogen bodies; glycogen depletion and lipid augmentation. ...

1991-04-01

Enzyme induction in neonates after fetal exposure to antiepileptic drugs

Rice is a very important food staple that feeds more than half the world's population. Two major Asian cultivated rice (Oryza sativa L.) subspecies, japonica and indica, show significant phenotypic variation in their stress responses. However, the molecular mechanisms underlying this phenotypic variation are still largely unknown. A common link among different stresses is that they produce an oxidative burst and result in an increase of reactive oxygen species (ROS). In this study, methyl viologen (MV) as a ROS agent was applied to investigate the rice oxidative stress response. We observed that 93-11 (indica) seedlings exhibited leaf senescence with severe lesions under MV treatment compared to Nipponbare (japonica). Whole-genome microarray experiments were conducted, and 1,062 probe sets were identified with gene expression level polymorphisms between the two rice cultivars in addition to differential expression under MV treatment, which were assigned as Core Intersectional Probesets ...

2010-01-08

Attenuation by methyl mercury and mercuric sulfide of pentobarbital induced hypnotic tolerance in mice through inhibition of ATPase activities and nitric oxide production in cerebral cortex

The /sup 13/C-AP breath test is shown to be a convenient, noninvasive method to monitor velocity and capacity of P450-dependent AP N-demethylation in infancy and childhood. According to /sup 13/C-AP breath tests, neonates have a very low capacity to eliminate /sup 13/CO/sub 2/, which is only 15 to 21% of the activity in adults. During the first year of life AP N-demethylation increases to reach its maximum at about 2 years; afterwards a slight decrease occurs. In 25 neonates exposed prenatally to different antiepileptic drugs /sup 13/C-AP breath test was efficiently used to prove that cytochrome AP N-demethylation was considerably stimulated. After primidone/phenobarbitone, especially in combination with phenytoin, /sup 13/C elimination reaches and even surpasses the range for older children. Valproate exposure during fetal life is not consistently followed by a significant increase in AP N-demethylation. The enzyme induction demonstrated by ...

1983-01-01

Altered lauric acid metabolism in renal microsomes from spontaneously hypertensive rats (SHR)

This study is aimed at exploring the possible mechanism of hypnosis-enhancing effect of HgS or cinnabar (a traditional Chinese medicine containing more than 95% HgS) in mice treated with pentobarbital. We also examined whether the effect of HgS is different from that of the well-known methyl mercury (MeHg). After a short period (7 days) of oral administration to mice, a nontoxic dose (0.1 g/kg) of HgS not only significantly enhanced pentobarbital-induced hypnosis but also attenuated tolerance induction; while a higher dose (1 g/kg) of HgS or cinnabar exerted an almost irreversible enhancing effect on pentobarbital-hypnosis similar to that of MeHg (2 mg/kg) tested, which was still effective even after 10 or 35 days cessation of administration. To study comparatively the effects of different mercury forms from oral administration of MeHg and HgS on membrane ATPase activities of experimental mice, analysis of the Hg content in the cerebral cortex revealed that correlated with the decrease ...

2008-06-15

"3H thymidine an indicator of benzo(a)pyrene induced lung carcinogenesis: role of quercetin and curcumin

Studies investigated whether changes in omega- and (omega-1)-hydroxylation (OH) of lauric acid (LA) occurred in renal microsomes prepared from SHR compared to Wistar-Kyoto (WK) control rats. Systolic blood pressure in age-matched adult SHR and WKR were 189 +/- 3 and 123 +/- 4 mm Hg(anti X +/- SE) respectively (p < 0.001). No significant differences between SHR and WKR were seen in body weight, kidney weight or renal microsomal protein content. Renal microsomes, prepared from whole kidneys, were incubated with 10 mM NADPH and ["1"4C]LA at concentrations between 5-50 #mu#M. The 11- and 12-OH metabolites of LA were separated by HPLC using a reverse phase column with a methanol:water:acetic acid (62:37.8:0.2) mobile phase. Apparent (app) V/sub max/ values for 12-OH in WKR and SHR were 0.87 +/- 0.19 vs 1.48 +/- .11 nmoles/mg protein/min (p < 0.05), respectively, while values for 11-OH were 0.51 +/- 0.12 vs 0.60 +/- .07, respectively. No significant differences were found in app K/sub ...

1986-04-13

Disruption of contact inhibition in rat liver epithelial cells by various types of AhR ligands

Full text: Lung cancer is responsible for most of the cancer related deaths and calls for new approaches to control the menace. In the present study chemopreventive efficacy of curcumin and quercetin was investigated against benzo(a)pyrene (BP) induced lung carcinogenesis. The mice were segregated into five groups which included normal control, BP treated, BP+curcumin treated, BP+quercetin treated and BP+curcumin+quercetin treated groups. The morphological and histological analyses of tumor nodules confirmed lung carcinogenesis, after 22 weeks of single i.p. injection of BP at a dose of 100 mg/Kg body weight to mice. Tumor incidence and tumor multiplicity were observed to be 88% and 1.75, respectively in the BP treated mice. A statistically significant increase in the uptake of "3H thymidine indicative of increased DNA synthesis which in turn is the marker of uncontrolled cancer cell proliferation, was observed in the lung slices of BP treated mice. Further, BP ...

The natural background approach to setting radiation standards

The maintenance of a balance between cell gain and cell loss is essential for proper liver function. The exact role of aryl hydrocarbon receptor (AhR) in regulating cell proliferation and apoptosis of liver cells remains unclear, since ligand-dependent activation of AhR has been shown to induce cell cycle arrest, proliferation, differentiation or apoptosis, depending on the cellular model used. AhR can directly interact with retinoblastoma protein in hepatic cells, forming protein complexes that can efficiently block cell cycle progression by inducing G1 arrest, or to induce the expression of inhibitors of cyclin-dependent kinases, such as p271. On the other hand, it has been suggested that AhR could play a stimulatory role in cell proliferation, either directly or by mediating a release from contact inhibition. It is now generally accepted that progenitor cells exist in the liver, are activated in various liver diseases and can form a potential target cell population for both tumor ...

2004-09-15