Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “BENZOPYRENES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 505 records · Page 28Linked to original sources
PubMed1994

Age, smoking and the activity of the mono-oxygenase aryl hydrocarbon hydroxylase in isolated human peripheral blood monocytes.

Age-associated changes in the microsomal mono-oxygenase enzyme, aryl hydrocarbon hydroxylase (AHH), were investigated in peripheral blood monocytes isolated from young and elderly subjects. Young subjects were selected from the age group < 35 years; elderly subjects were > 70 years. AHH activity, expressed as nM 3-hydroxy benzopyrene formed/10(6) cells/h of incubation, was similar in young and elderly non-smokers (elderly = 6.7 +/- 1.8; young = 9.1 +/- 0.9; p > 0.05). In smokers, contrary to some previous reports, AHH activity was not significantly higher than in non-smokers of similar age (elderly smokers = 8.6 +/- 1.0; young smokers = 10.5 +/- 2.4; p > 0.05). There was no significant difference between young and elderly smokers (p > 0.05). We conclude that: (a) AHH activity is similar in young and old non-smoking individuals; (b) no significant differences were detected in in vivo induction of this enzyme activity between smokers and non-smokers.

Adult↗
PubMed1995

Model for the epigenetic mechanism of action of nongenotoxic carcinogens.

On the basis of studies with carcinogenic nickel compounds, we propose a new model of how epigenetic carcinogens might act. This model is based on the fact that nickel compounds induce an increase in chromatin condensation, causing neighboring genes that are actively expressed in euchromatin to be condensed into heterochromatin. Such redistribution in condensation of chromatin would probably only be transient were it not for the DNA cytosine methyl transferase enzyme, which through de novo methylation can cause genes to be inherited in an active state. Actively expressed genes have less cytosine methylation in their promoter whereas hypermethylation of cytosine in promoters is characteristic of inactive genes. Therefore, nickel, through induction of an enhanced condensation state of chromatin that results in the incorporation of critical genes such as the senescence and tumor suppressor genes into heterochromatin (ie, thread on a spool) and the subsequent methylation of this DNA, silences the genetic activity that might be essential for maintenance of a normal cell. This model is consistent with the literature on cytosine methylation and is also consistent with studies of nickel carcinogenesis showing that it increases cytosine methylation. It is also consistent with nickel carcinogenesis being synergistic with many other mutagenic carcinogens (ie, x rays, benzopyrene, or ultraviolet light), which has always suggested that it has a unique component that is not part of the mechanism of these mutagenic carcinogens.

Animals↗
PubMed1998

Involvement of phosphoinositide 3-kinase in regulation of adhesive activity of highly metastatic hepatoma cells.

We have established hepatoma clones from benzopyrene-treated liver cells, one of which (G-5) shows extensive metastasis to the lung when injected subcutaneously into mice [Tanigaki, Y. et al. (1995) Invasion Metastasis 15, 70-80]. In the present study, we performed in vitro assays suitable for examination of the adhesive and invasive properties of the highly metastatic cells. G-5 cells efficiently entered the pores of fibronectin-coated filters. Treatment of the cells with an inhibitor of phosphoinositide 3-kinase (PI 3-kinase), wortmannin, significantly impaired the invasive activity. A structurally unrelated inhibitor, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) also prevented invasion. Both inhibitors suppressed cell adhesion to fibronectin-coated dishes. G-5 cells were next transfected with a mutant regulatory subunit (Deltap85) of PI 3-kinase, which was expected to impair the function of PI 3-kinase. The transfectants showed suppressed adhesion to the dishes and did not efficiently migrate into the filters. The lower adhesive ability of the transfected cells was not further affected by inhibitors of PI 3-kinase. Thus, PI 3-kinase activity contributes significantly to the adhesive and invasive properties of G-5 cells.

Androstadienes↗
PubMed1983

Induction of drug-metabolizing enzymes by tricyclic antidepressants in human liver: characterization and partial resolution of cytochromes P-450.

Drug-metabolizing enzyme activities were determined in liver microsomes from six kidney-transplant donors, one tricyclic antidepressant-treated and five untreated donors. The tricyclic antidepressant treatment modifies neither the overall cytochrome P-450 content of the liver, nor enzymatic activities of 4-nitroanisole demethylase, aniline hydroxylase, epoxide hydrolase and glutathione S-transferase. Only benzphetamine and ketotifen demethylation and conjugation of bilirubin with UDP-glucuronic acid are markedly augmented (more than two-fold). Separation of the different cytochrome P-450 fractions on a DEAE cellulose column indicates a modification of the elution pattern: the fraction increased by tricyclic antidepressants is responsible for the enhanced monooxygenase activity towards benzopyrene and benzphetamine.

Adult↗
PubMed1985

Immunoquantification of epoxide hydrolase and cytochrome P-450 isozymes in fetal and adult human liver microsomes.

Epoxide hydrolase and three cytochrome P-450 isozymes were immunochemically determined in microsomes from adult and fetal human liver and tentatively correlated with some enzyme activities. The P-450 isozymes 5, 8 and 9 present in adult liver could not be positively correlated with the total cytochrome P-450 concentration spectrophotometrically determined. In fetal liver microsomes, isozyme 8 could not be detected by either electrophoretic or immunochemical procedures. Isozyme 5 was the major isozyme present in the fetal liver and its concentration increased in close relation with the total P-450 level. As shown previously, arylhydrocarbon hydroxylase activity was related to the concentration of isozyme 8 in adult liver. In fetal preparations, the absence of isozyme 8 was associated with a very low arylhydrocarbon hydroxylase activity. Aldrin epoxidase and benzphetamine-N-demethylase activities were correlated with isozyme 5 concentration, but with different slopes for adult and fetal microsomes: adult preparations catalyzed these two reactions more efficiently. Conversely, the dehydroepiandrosterone 16 beta-hydroxylase, also associated with isozyme 5 concentration, was more active in fetal than in adult microsomes. Moreover, if acetanilide hydroxylase increased with isozyme 5 concentration in adult samples, no correlation occurred between activity and P-450 isozyme level in fetal microsomes. Hydroxylations of lauric acid in positions 11 and 12 and of dehydroepiandrosterone in position 16 alpha increased with total P-450 concentration but not with isozyme concentrations whatever the age considered. Lastly, epoxide hydrolase activity towards benzopyrene 4,5-oxide was closely associated with its immunochemically determined level. These results clearly suggest that multiple mechanisms are involved in the regulation of different drug-metabolizing enzymes in the human fetus.

Aging↗
PubMed1997

A point mutation responsible for defective function of the aryl-hydrocarbon-receptor nuclear translocator in mutant Hepa-1c1c7 cells.

A 3,4-benzopyrene-resistant mutant clone (c4) of the mouse hepatoma Hepa-1c1c7 cell line was examined for the mutation that causes the defective function of aryl-hydrocarbon receptor (AHR) nuclear translocator (Arnt). Arnt dimerizes with AHR and mediates the induction signal of aryl-hydrocarbon hydroxylase activity. The Arnt cDNAs of c4 cells were cloned by reverse-transcription/PCR to compare the sequences with that of wild-type Arnt cDNA. The Arnt cDNA of c4 cells was found to have a single point mutation, leading to replacement of Gly326 with Asp between two internal repeats in the highly conserved Per-Arnt-Sim (PAS) domain, PAS A and PAS B. The inability of [Asp326]Arnt/AHR heterodimers to enhance reporter gene transcription under the control of the CYP1A1 gene promoter and enhancer confirmed that the G326-->D substitution was a causative mutation. While fluorescence microscopy and coimmunoprecipitation experiments showed that this mutant form of Arnt was not changed from wild-type Arnt in terms of nuclear localization or heterodimer formation with AHR, the binding activity of the [Asp326]Arnt x AHR heterodimer to the xenobiotic-responsive element was reduced markedly. Determination of the turnover rate in COS-7 cells transfected with expression plasmids for mutant Arnt or normal Arnt showed that the mutant protein turned over with an accelerated rate compared with that of the normal. Moreover, the mutant protein displayed increased proteolytic digestibility in vitro with various proteases.

Amino Acid Sequence↗
PubMed1978

Crankcase oils: are they a major mutagenic burden in the aquatic environment?

Fractions from used crankcase oil enriched in polyaromatic hydrocarbons induced revertant colonies in Salmonella typhimurium strain TA 98 when activated by rat or trout liver extracts. The mutagenic activity was not due to benzopyrene or benzanthracene. Fractions from various crude and refined petroleums were nonmutagenic. Among various petroleum hydrocarbons entering inland and coastal waters, used crankcase oils may represent a major mutagenic burden.

Animals↗
PubMed2004

Chemically induced DNA hypomethylation in breast carcinoma cells detected by the amplification of intermethylated sites.

INTRODUCTION: Compromised patterns of gene expression result in genomic instability, altered patterns of gene expression and tumour formation. Specifically, aberrant DNA hypermethylation in gene promoter regions leads to gene silencing, whereas global hypomethylation events can result in chromosomal instability and oncogene activation. Potential links exist between environmental agents and DNA methylation, but the destabilizing effects of environmental exposures on the DNA methylation machinery are not understood within the context of breast cancer aetiology. METHODS: We assessed genome-wide changes in methylation patterns using a unique methylation profiling technique called amplification of intermethylated sites (AIMS). This method generates easily readable fingerprints that represent the investigated cell line's methylation profile, based on the differential cleavage of DNA with methylation-specific isoschisomeric restriction endonucleases. RESULTS: We validated this approach by demonstrating both unique and reoccurring sites of genomic hypomethylation in four breast carcinoma cell lines treated with the cytosine analogue 5-azacytidine. Comparison of treated with control samples revealed individual bands that exhibited methylation changes, and these bands were excized and cloned, and the precise genomic location individually identified. In most cases, these regions of hypomethylation coincided with susceptible target regions previously associated with chromosome breakage, rearrangement and gene amplification. Similarly, we observed that acute benzopyrene exposure is associated with altered methylation patterns in these cell lines. CONCLUSION: These results reinforce the link between environmental exposures, DNA methylation and breast cancer, and support a role for AIMS as a rapid, affordable screening method to identify environmentally induced DNA methylation changes that occur in tumourigenesis.

Azacitidine↗
PubMed1981

Studies on aspirin derivatives with very little side effect. II. Potent platelet anti-aggregant activity and no mutagenicity of aspirin-isopropylantipyrine (AIA).

The effect of a new aspirin derivative, aspirin-isopropylantipyrine (AIA), with very little gastric ulcerogenic activity and very slight acute toxicity and with analgesic, antipyretic anti-inflammatory, and platelet aggregation inhibitory activities was evaluated in vitro and ex vivo and compared with those of aspirin and isopropylantipyrine (IA). In vitro, AIA, aspirin and IA (50-200 microM) caused concentration-dependent inhibition of collagen-induced aggregation in rabbit platelets although AIA was several-fold more active than the others Arachidonic acid-induced aggregation was inhibited by all three agents (200 microM) in the following magnitude; IA greater than aspirin greater than AIA. Three agents did not influence primary ADP-induced aggregation. The in vitro effects on the release-inducing aggregants were confirmed by ex vivo experiments in rats. These demonstrated that AIA and aspirin (50 mg/kg) exhibited almost identical inhibitory potencies in the extent and the rate of collagen-induced aggregation 4 h after subcutaneous injection. AIA was still effective 24 h after administration as well as aspirin. IA was less effective, differing from the results in vitro. AIA had no effect on plasmin activity and blood flow through the common carotid artery. AIA (1 mM) maintained spreading and beating of myocardial cells in a serum-free culture. As special toxicity trials on AIA mutagenecity tests were made by the Rec-assay with Bacillus subtilis, by the plate culture with Escherichia coli, and by the Ames system with Salmonella typhimurium. AIA was found to have no mutagenic effect under any of those methods and to have no effect on the mutagenic action of 3, 4-benzopyrene under the liver microsome test using the Ames system.

Animals↗
PubMed2006

Synthetic and natural coumarins as antioxidants.

Coumarins, an old class of compounds, are naturally occurring benzopyrene derivatives. A lot of coumarins have been identified from natural sources, especially green plants. These natural compounds have served as valuable leads for further design and synthesis of more active analogs. The pharmacological and biochemical properties and therapeutic applications of simple coumarins depend upon the pattern of substitution. Coumarins have attracted intense interest in recent years because of their diverse pharmacological properties. Among these properties, their antioxidant effects were extensively examined. In this review, plant derived coumarins and their synthetic analogs will be systematically evaluated based on their plant origin, structure-activity relationship and antioxidant efficacy. Owing their diverse effects and inconclusive results from different in vitro studies, the mechanism of their action has not yet been fully understood and the correlation of effects with chemical structure is not conclusive at the moment. It is the objective of this review will be to summarize experimental data for different coumarins used as antioxidant agents, because promising data have been reported for a series of these agents. In addition, their ability to bind metal ions represents an additional means of modulating their pharmacological responses.

Animals↗
PubMed2005

Synthetic and natural coumarins as cytotoxic agents.

Coumarins, an old class of compounds, are naturally occurring benzopyrene derivatives. A lot of coumarins have been identified from natural sources, especially green plants. The pharmacological and biochemical properties and therapeutic applications of simple coumarins depend upon the pattern of substitution. Coumarins have attracted intense interest in recent years because of their diverse pharmacological properties. Among these properties, their cytotoxic effects were most extensively examined. In this review, their broad range of effects on the tumors as shown by various in vitro and in vivo experiments and clinical studies are discussed. Hence, these cytotoxic coumarins represent an exploitable source of new anticancer agents, which might also help addressing side-toxicity and resistance phenomena. These natural compounds have served as valuable leads for further design and synthesis of more active analogues. In this review, plant derived coumarins and their synthetic analogues were systematically evaluated based on their plant origin, structure-activity relationship and anticancer efficacy. Owing the their diverse effects and inconclusive results from different in vitro studies, the mechanism of their action is not yet fully understood and correlation of effects with chemical structures is not conclusive at the moment. It is the objective of this review to summarize experimental data for different coumarins, used as cytotoxic agents, because promising data have been reported for a series of these agents. Yet, the results from different coumarins with various tumor lines are contradictory in part. We therefore conclude that there is still a long way to go until we know which cytotoxic agent will clinically be suitable for what tumor entity for treatment. Their ability to bind metal ions represents an additional means of modulating their pharmacological responses.

Animals↗
PubMedDate not supplied

The effect of leukotriene D4 on the patency of nasal passage in the guinea pig.

We investigated the effect of leukotriene D4(LTD4) on the patency of the nasal passage in nonsensitized and sensitized guinea pigs (GPs). The change in nasal patency was measured by acoustic rhinomanometry (AR). The change of volume from the nostril to 2 cm into the nasal cavity showed significant reduction at 30 minutes and 6 hours after instillation of LTD4 in nonsensitized GPs. These findings were also seen in nonsensitized and sensitized GPs with systemic administration of carboxyl cellulose. However, neither nonsensitized nor sensitized GP with systemic administration of benzopyren hemihydrate(ONO-1078) showed any changes in nasal patency. These results indicated that the LT was a potent medication to induce nasal obstruction of late reaction in GP.

Airway Resistance↗
PubMed1976

[The role and functions of the lung in equilibrium of the internal milieu. Protein metabolism and enzyme systems].

The different anatomical zones of the lung show a high degree of variation in metabolic function, involving many protein molecules and complex enzyme systems. Recent data in the literature concerning such activity are described with respect to bradykinin, fibrinolysis, haemostasis, angiotensin, serotonin, catecholamines, prostaglandins, vaso-active amines, the protease-antiprotease system and benzopyrene-hydroxylase.

Capillaries↗
PubMed1999

[Elements of epidemiology and initiation of carcinogenesis in carcinomas of the upper aerodigestive tract. Future therapeutic consequence?].

The study of epidemiology and of the carcinogenesis in epidermoid carcinomas of the upper aerodigestive tract shows that their occurrence is not random. Tobacco abuse plays a major role, especially because of benzopyrene, mutagen of the P53 gene, however it is associated with many other potentiating factors: alcohol, metals, hydrocarbures, virus, food, climate, genetic fragility that create genetic lesions at the origin of carcinogenesis. The latter occurs as "field cancerization" with multiple alterations of the mucosa and general attack of the control systems of the differentiation, growth and cell apoptosis which usually protect the cell against the phenomena of carcinogenesis. The P53 protein gene, retinoid receptors as well as the system of detoxifying glutathion S transferase are modified at the very early stage of these diseases, these abnormalities can be logically related to epidemiological data. These data lead us therefore to imagine complementary specific reverting therapies of induced genetic abnormalities, through the reexpression of non mutated gene encoding P53 protein and the use of retinoid. These various modalities are reported hereafter.

Age Factors↗
PubMed1999

Imprinting: perinatal exposures cause the development of diseases during the adult age.

Since the early reports linking the development of clear cell cervicovaginal adenocarcinoma in young women with diethylstilbestrol treatment of their mothers during pregnancy, it became clear that perinatal exposure to several substances may induce irreversible alterations, that can be detected later in life. Current evidence suggests that these substances induce, by the mechanism of imprinting, alterations of the differentiation of several cell-types, resulting in the development of disease during the adult age. The most known delayed effects to prenatal exposure to agents displaying hormone action, pollutants, food additives and natural food components, substances of abuse and stress by the mechanism of imprinting are described. Among them, estrogens, androgens, progestins, lead, benzopyrenes, ozone, dioxins, DDT, DDE, methoxychlor, chlordecone, parathion, malathion, polychlorobiphenyls, pyrethroids, paraquat, food additives, normal food constituents, tetrahydrocannabinol, cocaine and opiates. It is concluded that perinatal exposure to several agents causes irreversible changes that determine health conditions during adulthood. Several diseases developing during adulthood probably were determined during early stages of life, under the effect of exposure or preferential mother's diet during pregnancy. Regulations to avoid these early exposures may contribute to an important improvement of health conditions of humankind.

Environmental Pollutants↗
PubMed1979

[Demonstration of "hydroxylase" and "epoxide hydrase" activities in preparations of nucleoli isolated from rat liver].

Aryl hydrocarbon hydroxylase (AHH) activity and epoxyde hydrase (EH) activity have been found in Rat liver nucleoli obtained from untreated (C) and methylcholanthrene (MC) pretreated Rats. Electron microscopic observations of nucleolar preparations did not reveal significant contamination either by intact nuclei or by nuclear membranes. Very low but detectable activity of NADPH cytochrome C reductase was found in the nucleoli. Nucleolar preparations revealed little AHH activity (12-18 pmoles/min/mg). AHH was inducible by MC in nuclei but not in nucleoli. The presence of EH in nucleoli was demonstrated with phenanthrene 9,10-oxide (550-620 pmoles/min/mg) and benzopyrene 4,5-oxide (92-116 pmoles/min/mg). These values were lower than those obtained using intact nuclei. The addition of TCPO (10(-4) M) inhibited EH activity.

Animals↗
PubMed2000

[HPLC determination of PAHs from electric power plant by UVD-FLD connected in series].

An HPLC method of UVD-FLD connected in series was used to detect naphthalene, biphenyl, fluorene, phenanthrene, anthracene, fluoranthene, 2-methyl-anthracene, chrysene, benzanthracene, benzfluoranthene [b], benzfluoranthene[k], benzopyrene PAH compounds in electricity plant environment. A CLC-ODS column (150 mm x 6.0 mm i.d.) with acetonitrile-water(85:15, V/V) as mobile phase and UV detector set at 250 nm and fluorescent detector set at lambda ex295 nm and lambda em427 nm were used. These 12 PAHs can be separated completely by this method. The earlier eluted eight PAHs were detected by UVD and the rest were detected by FLD. The minimum detectable concentrations of the 12 PAHs were 0.002 mg/L-0.1 mg/L. Satisfactory results were obtained in the analysis of PAH compounds in waste water, flue gas and flyash from several electric power plant in Hunan Province.

Chromatography, High Pressure Liquid↗
PubMed2000

[Effects of baicalin on liver microsomal cytochrome P450 system].

AIM: To investigate the effect of baicalin on liver microsomal cytochrome P450 system and the mechanism of liver protective action of baicalin. METHODS: Liver microsomal cytochrome P450, b5, aminopyrin N-demethylase (ADM), 7-ethoxycoumarin O-deethylase (ECD) and benzopyrene hydroxylase (AHH) activity were quantitated by UV chromatography. Activities of six cytochrome P450 isoforms were assayed with Western Blotting. RESULTS: Baicalin increased liver microsomal cytochrome. P450 level and ADM, ECD and AHH activity significantly. The three P450 isoforms, 1A1, 2B1 and 2C11, were also induced selectively by baicalin, but the b5 level, 3A2, 2D1 and 2E1 were not induced. CONCLUSION: Baicalin increases liver microsomal cytochrome P450 level and induces selectively 1A1, 2B1 and 2C11 of P450 isoforms in mice.

Animals↗