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 487 records · Page 27Linked to original sources

Interactions between neoplastic cells with different metastasizing capacity and platelet function.

We have examined the effects on platelet function of two sublines (M4 and M9) derived from spontaneous lung nodules of a benzopyrene-induced murine fibrosarcoma (m FS6). The subline M4 was more metastatic and the subline M9 less metastatic than the primary tumour. Only the more malignant cells were able to induce irreversible aggregation of human platelets; this effect was concentration-dependent and was associated with the release of serotonin by platelets. Both aggregation and release were inhibited by preincubation of platelets with ASA, not by preincubation of the cells. The supernatants of cell suspensions had no aggregating activity. However, the neoplastic cells in culture media released an activity directly stimulating platelet aggregation and potentiating the platelet response to ADP; again, this activity was higher for the more malignant cells and the effects were inhibited by preincubation of platelets with ASA. These results suggest a role for platelets in the development of tumour metastases.

Adenosine Diphosphate↗

Failure to warfarin to affect the tissue factor activity and the metastatic potential of murine fibrosarcoma cells.

Vitamin K deficiency, either dietary or pharmacologically induced by warfarin, was unable to affect the metastatic capacity of cells from a benzopyrene-induced fibrosarcoma in C57BL/6J mice. The same cells had a procoagulant activity, of tissue thromboplastin type, which was also completely unaffected by vitamin K antagonism or deficiency. In another murine model of spontaneous metastasis we previously suggested that depression of a particular procoagulant such as a direct factor X activator might contribute to the antimetastatic activity of warfarin. The failure of vitamin K deficiency to affect both the procoagulant and the metastatic capacity of the model reported here offers strong negative support to the same concept.

Animals↗

Comparative effects of T-2 toxin and diacetoxyscirpenol on drug metabolizing enzymes in rat tissues.

The effects of T-2 toxin and diacetoxyscirpenol on tissue drug-metabolizing enzymes in young male rats were compared. Mycotoxicoses were produced by daily oral administration of toxins at 1.0 mg/kg body weight for 1, 4 or 8 days. Many hepatic, renal and pulmonary oxidative and conjugative enzymes were measured in animals killed 24 hr following the last administration. The effects of the two trichothecene mycotoxins were generally similar. In liver the decrease in microsomal and cytosolic proteins paralleled the decline in total plasma proteins or the increase in plasma GOT activity. Hepatic microsomal cytochrome P-450 decreased in rats receiving trichothecenes for 8 days. This effect was more marked when aminopyrine, benzphetamine, ethylmorphine and ethoxycoumarin dealkylations or aniline and benzopyrene hydroxylations were measured. p-nitrophenol glucuronyltransferase activity was enhanced in animals receiving at least one administration of trichothecenes, whereas there was no change in conjugation to glutathione or acetate. In other tissues, there was no change in any renal enzymes whereas a significant rise in pulmonary monooxygenase was observed in T-2 toxin administered to rats for 4 or 8 days.

Animals↗

Application of biomarkers in population studies for respiratory non-malignant diseases.

Though the use of biomarkers has been mainly suggested for cancer studies, the possibility of its use in non malignant disease is considered. Markers of internal dose, markers of biologically effective dose and markers of early biologically effect have been typically used in basic research and, more recently, in epidemiology to characterize genotoxic carcinogenic agents. These markers (e.g. adducts to DNA or proteins) may be used mainly in the presence of chronic exposure to toxic agents (e.g. benzene or benzopyrene), additional markers such as carboxyhemoglobin, expired air to measure various VOC and heavy metals in biological fluids are also considered in the paper. Since airway obstructive disease (asthma, chronic bronchitis, emphysema) are the main disorders influenced by environmental factors (including air pollution), markers of individual susceptibility, such as atopy increased responsiveness of airways, initial level of lung function, must be considered for a more precise evaluation of the relationship between environmental exposure and health effects. Currently, the application of the determination of markers of exposure in non malignant disorders is very limited. In fact, the relationships between acute adverse respiratory effects and the exposure to air pollutants appears difficult since markers for common air pollutants are not available, and their detection appears difficult in acute conditions. Characterization of long term exposure may be performed in organ fluids (blood, urine, saliva) however it is important to recognize that concentration at that level may not reflect that observed in the target organ (e.g. lung).

Air Pollutants↗

A short-term in vitro assay for promoter substances using human lymphoblastoid cells latently infected with Epstein-Barr virus.

We designed a short-term in vitro assay for detecting tumor promoters, utilizing the activation of Epstein-Barr virus (EBV) expression in EBV genome-carrying human lymphoblastoid cells. This system is composed of EBV-non-producer Raji cells as the indicator, n-butyrate as the EBV-inducer, and the test substance. After addition of the latter 2 components to the culture medium, the cells are cultivated for 48 h at 37 degrees C and the ratio of EBV early antigen (EA)-expressing cells was assessed using immunofluorescence. This assay system allows for a rapid detection of the activity of the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and its related compounds and also of the Euphorbiaceae plant extracts containing such active principles. Among several microbial products tested, teleocidin, an indole-alkaloid produced by a Streptomyces species, was also detected and had an activity level comparable to that of TPA. Other promoters, such as anthralin, phenol, Tween 60 and 80 and the carcinogenic ("initiator") substances including benzopyrene, did not react with the system. The test is simple to perform, reproducible and should be applicable for mass-screening of promoter substances in the environment.

Carcinogens↗

Solid state and solution studies of a vanadium(III)-L-cysteine compound and demonstration of its antimetastatic, antioxidant and inhibition of neutral endopeptidase activities.

Reaction of one equivalent of vanadium(III) chloride with three equivalents of l-cysteine(H2Cys) in methyl alcohol affords a VIII-Cys compound that is formulated as [VIII(Hcys)3].2HCl.2.5H2O 1. The solid state characterization of 1 was performed by microanalysis, circular dichroism (CD) and infrared studies as well as room temperature magnetic susceptibility. These studies have shown coordination of each HCys- ligand to the VIII atom through an amine nitrogen and a carboxylate oxygen atoms. Solution studies of 1 were carried out in water and methanol by UV-visible, CD and electron paramagnetic resonance (EPR) spectroscopies. According to these studies, it was evident that despite the progressive oxidation of 1 to oxovanadium(IV) species, some V(III) species were also present in solution after several hours. Compound 1, VIVOSO4.5H2O and l-cysteine were examined for their total antioxidant capacity (TAC) and lag time. Compound 1 exhibited significantly greater total antioxidant capacity and lag time values than l-cysteine. VIVOSO4.5H2O did not show any total antioxidant capacity or lag time. The inhibition of neutral endopeptidase (NEP) activity caused by 1, VIVOSO4.5H2O and thiorphan was also measured. Compound 1, at a concentration of 10(-3) M, showed inhibition of NEP activity as potent as thiorphan at 10(-6) M, while VIVOSO4.5H2O in the same concentration exhibited less than 50% inhibitory activity than that of thiorphan at 10(-6) M. Moreover, the antimetastatic effects of compound 1, l-cysteine and VIVOSO4.5H2O were examined on Wistar rats, treated with 3,4-benzopyrene. The results revealed that 1 prevents significantly lung metastases (only 9.5% of animals treated with 1 showed metastases), whereas 47-52% of the rats of the control group and those treated with l-cysteine and VIVOSO4.5H2O exhibited metastases.

Animals↗

Comparison of the vascular relaxant effects of ATP-dependent K+ channel openers on aorta and pulmonary artery isolated from spontaneously hypertensive and Wistar-Kyoto rats.

The vasorelaxant actions of adenosine 5'-triphosphate (ATP)-dependent K+ channel openers and sodium nitroprusside in isolated thoracic aorta and pulmonary artery of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats (14-18 weeks old) were investigated. Cumulative addition of sodium nitroprusside and different ATP-dependent K+ channel openers (pinacidil, cromakalim, nicorandil, 2-(2"(1",3"-dioxolone)-2-methyl-4-(2'-oxo-1'-pyrrolidinyl)-6-nitro -2H-1-benzopyren (KR-30450) and aprikalim) to these preparations caused a concentration-dependent relaxation of noradrenaline-pre-contracted aorta and pulmonary artery from both strains. The relative order of relaxation potency, estimated by comparing the IC50, was sodium nitroprusside > KR-30450 > aprikalim > or = cromakalim > pinacidil > nicorandil in pulmonary artery and aorta from both strains. At high concentrations (> or =1 microM), cromakalim, aprikalim and KR-30450 produced a greater percentage relaxation in SHR aorta than in WKY aorta. However, there was no apparent difference between SHR and WKY in the relaxation response to all drugs tested on the pulmonary artery. The effects of cromakalim, aprikalim, pinacidil and KR-30450 observed in aorta and pulmonary artery were significantly attenuated by 3 microM glibenclamide. 6-Anilino-5,8-quinolinequinone (LY 83583, 1 microM), a soluble guanylate cyclase inhibitor, abolished the vasorelaxant effects of nicorandil and sodium nitroprusside. In conclusion, sodium nitroprusside and ATP-dependent K+ channel openers cause relaxation of noradrenaline-pre-contracted aorta and pulmonary artery from both strains. However, all the drugs tested failed to cause selective relaxation of the pulmonary artery relative to the thoracic aorta.

Adenosine Triphosphate↗

Gas chromatographic-mass spectrometric study of the oil fractions produced by microwave-assisted pyrolysis of different sewage sludges.

The pyrolysis of sewage sludge was studied in a microwave oven using graphite as microwave absorber. The pyrolysis temperature ranged from 800 to 1000 degrees C depending on the type of sewage sludge. A conventional electrical furnace was also employed in order to compare the results obtained with both methods. The pyrolysis oils were trapped in a series of condensers and their characteristics such as elemental analysis and calorific value were determined and compared with those of the initial sludge. The oil composition was analyzed by GC-MS. The oils from the microwave oven had n-alkanes and 1-alkenes, aromatic compounds, ranging from benzene derivatives to polycyclic aromatic hydrocarbons (PAHs), nitrogenated compounds, long chain aliphatic carboxylic acids, ketones and esters and also monoterpenes and steroids. The oil from the electric oven was composed basically of PAHs such as naphthalene, acenapthylene, phenanthrene, fluoranthene, benzo[a]anthracene, benzofluoranthenes, benzopyrenes, indenepyrene, benzo[ghi]perylene, and anthanthrene. In contrast, these compounds were not produced in the case of microwave-assisted pyrolysis.

Gas Chromatography-Mass Spectrometry↗

Nondestructive biomarkers of exposure to endocrine disrupting chemicals in endangered species of wildlife.

This paper explores the problem of endocrine disrupting chemicals (EDCs) from the ecotoxicological point of view, focusing on nondestructive biomarkers of exposure to EDCs for risk assessment of endangered species of wildlife. Several EDCs, such as polyhalogenated aromatic hydrocarbons and toxic metals, tend to be biomagnified in the terrestrial and particularly the marine food chains. Top predators tend to accumulate high concentrations of these contaminants which places them in a situation of high toxicological risk. Hence, there is a need to develop nondestructive techniques, such as nondestructive biomarkers, for hazard assessment, protection, and conservation of endangered species exposed to EDCs. The biological materials proposed for this approach (for example blood, faeces, fur, skin biopsy specimens) are easily obtained with minimal stress for individuals and populations. Some validation data are reported on porphyrins in sea bird excreta (Larus dominicanus, Phalacrocorax olivaceus, Pelecanus occidentalis thagus), as nondestructive biomarkers of exposure to organochlorines, and on benzopyrene monooxygenase activities in marine mammal skin biopsy specimens (Stenella coeruleoalba, Balaenoptera physalus), as early indicators of exposure to p,p'-DDE and other endocrine disrupting organochlorines.

Animals↗

Laser-induced multidimensional fluorescence spectroscopy in Shpol'skii matrixes with a fiber-optic probe at liquid helium temperature.

Improved methodology for chemical analysis via laser-excited Shpol'skii spectrometry at liquid helium temperature (4.2 K) is reported. Sample freezing is performed in a matter of seconds with the aid of a fiber-optic probe directly inserted into the liquid cryogen. Emission wavelength time matrixes, excitation emission wavelengths, and time-resolved excitation emission wavelengths are rapidly collected with the aid of a pulsed tunable dye laser, a high-resolution spectrograph, and an intensified charged-couple device. Data reproducibility for qualitative and quantitative analysis purposes and analytical figures of merit are demonstrated for several polycilic aromatic hydrocarbons/n-alkane systems. Fluorescence lifetime differences from analyte molecules occupying different crystallographic sites in the same frozen matrix are presented for the first time. The potential of our approach is illustrated for the direct analysis of a benzopyrene fraction typically encountered in HPLC analysis of polycyclic aromatic hydrocarbons.

Journal Article↗

Second-order advantage achieved by unfolded-partial least-squares/residual bilinearization modeling of excitation-emission fluorescence data presenting inner filter effects.

A second-order multivariate calibration approach, based on a combination of unfolded-partial least-squares with residual bilinearization (U-PLS/RBL), has been applied to fluorescence excitation-emission matrix data for multicomponent mixtures showing inner filter effects. The employed chemometric algorithm is the most successful one regarding the prediction of analyte concentrations when significant inner filter effects occur, even in the presence of unexpected sample components, which require strict adherence to the second-order advantage. Results for simulated fluorescence excitation-emission data are described, in comparison with the classical approach based on parallel factor analysis and other second-order algorithms, including generalized rank annihilation, bilinear least squares combined with residual bilinearization and multivariate curve resolution-alternating leastsquares. A set of experimental data was also studied, in which calibration was performed with fluorescence excitation-emission matrices for samples containing mixtures of chrysene (the analyte of interest) and benzopyrene (which produced strong inner filter effect across the useful wavelength range). Prediction was made on validation samples with a qualitative composition similar to the calibration set, and also on test samples containing an unexpected component (pyrene). In this latter case, U-PLS/RBL showed a unique success for the analysis of the calibrated component chrysene, achieving the useful second-order advantage.

Calibration↗

Antibody-based nanoprobe for measurement of a fluorescent analyte in a single cell.

We report here the application of an antibody-based nanoprobe for in situ measurements of a single cell. The nanoprobe employs antibody-based receptors targeted to a fluorescent analyte, benzopyrene tetrol (BPT), a metabolite of the carcinogen benzo[a]pyrene (BaP) and of the BaP-DNA adduct. Detection of BPT is of great biomedical interest, since this species can serve as a biomarker for monitoring DNA damage due to BaP exposure and for possible precancer diagnosis. The measurements were performed on the rat liver epithelial clone 9 cell line, which was used as the model cell system. Before making measurements, the cells were treated with BPT. Nanoprobes were inserted into individual cells, incubated 5 min to allow antigen-antibody binding, and then removed for fluorescence detection. We determined a concentration of 9.6+/-0.2x10(-11) M for BPT in the individual cells investigated. The results demonstrate the possibility of in situ measurements inside a single cell using an antibody-based nanoprobe.

Animals↗

Budesonide exerts its chemopreventive efficacy during mouse lung tumorigenesis by modulating gene expressions.

Budesonide, a glucocorticoid, was proven to be a highly effective agent in preventing the development of lung tumors in A/J mice. In a lung tumor bioassay, budesonide produced 70% inhibition of tumor multiplicity and 94% reduction of total tumor load compared to benzopyrene (B[a]P) treated mice. Gene expression array analysis was performed on mouse lung tumors from this bioassay using Affymetrix U74Av2 GeneChips to determine gene expression changes associated with budesonide treatment. We found 363 genes that were changed between lung tumors induced by treatment with B[a]P and similar tumors treated with budesonide. Among them, 243 genes were overexpressed and 120 genes were underexpressed after budesonide treatment. In addition, 108 genes differentially expressed during mouse lung tumorigenesis (50 genes overexpressed and 58 genes underexpressed) were modulated back to normal levels after budesonide treatment when compared with the controls group. These genes are involved in a broad range of different pathways including control of cell cycle, signal transduction, and apoptosis and may play a role in the observed preventive effect. Our results suggest that budesonide exerts its effects of chemoprevention through growth arrest via Mad2/3 and through apoptosis via Bim/Blk and, by inference, caspase-8/9. Using the pathway visualization tool GenMapp, G protein pathway and MAPK cascade were also regulated by budesonide. Thus, we have determined, for the first time, the expression profiles of genes modulated by budesonide during murine lung tumorigenesis. Our results indicate that the chemopreventive effects of budesonide in the mouse lung tumorigenesis assay involved increase and decrease expression of a wide variety of genes in multiple signaling pathways.

Animals↗

The effect of diet and 1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane (DDT) on microsomal hydroxylating enzymes and on sensitivity of rats to carbon tetrachloride poisoning.

1. Protein-depleted rats are resistant to the lethal effects of carbon tetrachloride. The LD(50) is 6.4ml./kg. in stock rats and 14.7ml./kg. in rats fed on protein-free diets. 2. Protein-depleted rats are resistant to carbon tetrachloride in its effect on the liver as judged by histology, accumulation of liver water, and plasma enzyme and bilirubin measurement. 3. The protection is present after feeding rats on a no-protein diet for 4 days. It is present after feeding rats on a 3%-casein diet, and partly found after feeding rats on a 6%-casein diet. 4. The activities of the microsomal enzymes that demethylate Pyramidon and hydroxylate benzopyrene in the liver fall by over 80% in rats fed on the no-protein diet for 4 days or more, or in rats fed on a 3%-casein diet. A 50% fall is found in rats fed on a 6%-casein diet. 5. A single dose of DDT or three doses of phenobarbitone cause increased microsomal enzyme activity in protein-depleted rats. 6. The animals are then sensitive to the lethal and liver-damaging effects of carbon tetrachloride. 7. DDT dosage also leads to increased sensitivity to carbon tetrachloride in rats fed on stock diets. 8. These findings support the hypothesis that carbon tetrachloride is metabolized by microsomal enzymes to form the true toxic compound.

Journal Article↗

Enzymic oxidation of some alkylbenzenes in insects and vertebrates.

1. Oxidation rates of alkylbenzenes have been measured in 10000g supernatants of vertebrate livers, locust fat bodies and housefly abdomens. 2. Activity per g. of insect was greater in fly than locust preparations but both were of the same order as a range of vertebrate species. 3. Methyl groups of toluene and p-nitrotoluene were oxidized more rapidly than the side chains of higher homologues. 4. In the higher homologues hydroxylation occurred most readily at the alpha-methylene group and less readily at penultimate methylene and terminal methyl groups. 5. Oxidations in both vertebrates and insects were inhibited by piperonylbutoxide and similar synergists. 6. Oxidation activity was stimulated by pretreatment of rats, but not locusts, with phenobarbitone or 3,4-benzopyrene.

Animals↗

Sequence selectivity, a test of the nature of the covalent adduct formed between benzo[a]pyrene and DNA.

A theoretical study is presented of the energetic and structural properties of covalent adducts of benzo[a]pyrene and a DNA fragment. Energy optimisation is performed with the use of minimiser with constraints and an advanced semiempirical energy formula. Three types of adducts are studied: an external complex with the benzopyrene located in the DNA minor groove and two types of intercalative complexes with the carcinogen situated on the 3' side and 5' side of the covalently bound guanine. For each of the adducts the effects of DNA base sequence are examined. It is shown that the results for the intercalative complex with the carcinogen situated on the 5' side of the modified guanine correlate with the experimentally determined sequence preference.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

Scientific analysis of second-hand smoke by the tobacco industry, 1929-1972.

The 1972 U.S. surgeon general's report The Health Consequences of Smoking was the first to include a warning about exposure to second-hand smoke. Because the tobacco industry has a record of withholding the results of their research from the public, we searched the internal tobacco industry documents and compared internal industry research on second-hand smoke to what the industry published in the open scientific literature through 1972. We found chemical analyses, sensory evaluations, and discussions of sidestream cigarette smoke (the smoke emitted by the cigarette between puffs, the main component of second-hand smoke), beginning in 1929. American Tobacco Company research in the 1930s indicated that, compared with mainstream smoke, sidestream smoke was produced in larger quantities and contained, per cigarette, 2 times more nicotine and 12 times more ammonia. Research funded by the Tobacco Industry Research Committee in the 1950s revealed that sidestream smoke contained, per unit cigarette, higher concentrations of carcinogenic polycyclic aromatic hydrocarbons, per unit mass, including four times more 3,4 benzopyrene. In 1956 and 1957, respectively, Philip Morris and R. J. Reynolds also began to research sidestream smoke. In 1961, Philip Morris began to do sensory evaluation and modification of sidestream odor during product development. This sensory evaluation of sidestream smoke was the first biological testing of sidestream smoke by a tobacco company. Prior to the release of the 1972 U.S. surgeon general's report, the tobacco industry published the majority of its findings in the open scientific literature and does not appear to have perceived second-hand smoke as a threat to human health.

Disclosure↗

Induction of cytochrome P-450 in the Norway rat, Rattus norvegicus, following exposure to potential environmental contaminants.

Cytochrome P-450 (CYP) induction (consisting of increases in cellular RNA and protein content and associated catalytic activities) occurs predominantly in the liver, but also in small intestine, lung, kidney, and placenta, of Norway rats (Rattus norvegicus) exposed to certain types of potential environmental contaminants. The specific isoform(s) induced in the rat and the magnitudes of the increases observed depend upon the chemical nature of the xenobiotic. For instance, the predominant isoforms induced by nonhalogenated polycyclic aromatic hydrocarbons, such as petroleum derivatives and coal-tar constituents such as the benzopyrenes and the anthracenes, are those of the CYP1A subfamily. Polyhalogenated aromatic hydrocarbons, such as the halogenated dibenzodioxins, dibenzofurans, and biphenyls, may cause the induction of predominantly the CYP1A subfamily, predominantly the CYP2B subfamily, or mixed CYP1A- and CYP2B-type induction, depending upon the halogen substitution pattern. In contrast, the chlorinated hydrocarbon pesticides, such as DDT, dieldrin, chlordane, and mirex, cause almost exclusively the induction of isoforms of the CYP2B (and to a lesser extent the CYP3A) subfamilies. The commonly employed plasticizing agent di-(2-ethylhexyl)phthalate elicits predominantly induction of the CYP4A subfamily. Those xenobiotics that would be expected to be the most pervasive environmental contaminants are typically those that have also been found to cause the most profound CYP induction responses. Such chemicals are extremely lipophilic and tend to accumulate in animal tissues, especially fatty tissues such as the liver. The hepatic CYP induction response to such potential environmental contaminants is typical of the animals' response to lipophilic xenobiotics in general, and serves as a mechanism by which the excretion of such compounds from the body is facilitated.

Animals↗