Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Pyrenes”

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 1,045 records · Page 58Linked to original sources
PubMed1985

Isolation and characterization of rat liver cytosolic aldehyde dehydrogenases induced by phenanthrene or benzo[a]pyrene.

The cytosolic aldehyde dehydrogenase was isolated from the liver of Wistar rats treated with phenanthrene (non-carcinogenic) or benzo[a]pyrene (carcinogenic polycyclic aromatic hydrocarbon). The benzo[a]pyrene-induced enzyme has higher Km values for small aliphatic aldehydes and a lower molecular weight than the phenanthrene-induced enzyme. It is more resistant to changes of pH and to inhibition by disulfiram, but more sensitive to heat denaturation than the phenanthrene-induced enzyme. The phenanthrene-induced aldehyde dehydrogenase is very similar to the normal uninduced aldehyde dehydrogenase, whereas the benzo[a]pyrene-induced aldehyde dehydrogenase has common properties with the TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin)-induced enzyme and the hepatoma-specific enzyme.

Aldehyde Dehydrogenase↗
PubMed1985

A permeabilized cell system for studying regulation of aryl hydrocarbon hydroxylase: NADPH as rate limiting factor in benzo(a)pyrene metabolism.

The disadvantage of a whole cell system for studying the metabolism of xenobiotics is that some substrates and regulatory molecules do not readily cross the cell membrane. The present study describes a technique to permeabilize H-4-II-E rat hepatoma cells for the study of benzo(a)pyrene metabolism. NADPH is an essential cofactor in the in vitro microsomal metabolism of benzo(a)pyrene and has been shown by indirect measurement to be a rate limiting factor in mixed function oxidase activity in whole liver perfusion systems. The role of NADPH has not been directly demonstrated in an intact cell system. Using this permeabilized whole cell system it is possible to directly demonstrate that NADPH is rate limiting in the mixed function oxidation of benzo(a)pyrene.

Animals↗
PubMed1984

Rat liver homogenate (S9)-mediated binding of benzo[alpha]pyrene to DNA in V79 cells, V79 cell nuclei and aqueous solution.

The role of the target cell in determining the structures and the amounts of hydrocarbon-DNA adducts formed after hydrocarbon activation by an exogenous metabolic activation system was investigated by exposing intact cells of the Chinese hamster lung cell line V79, V79 cell nuclei and calf thymus DNA to benzo[a]pyrene (B[a]P) in the presence of a rat liver homogenate activation system (S9). The DNA was isolated, enzymatically degraded to deoxyribonucleosides and the B[a]P-deoxyribonucleoside adducts analyzed by high-performance liquid chromatography. Two major adducts were present in all samples; one formed by reaction of r-7, t-8-dihydroxy-t-9, 10-epoxy-7, 8, 9, 10-tetrahydro-B[a]P (anti-B[a]PDE) with the 2-amino group of deoxyguanosine, the other formed by reaction of a metabolite of 9-hydroxybenzo[a]pyrene (9-OH-B[a]P) with an unidentified deoxyribonucleoside. The ratios of the anti-B[a]PDE-DNA adduct to the 9-OH-B[a]P-DNA adduct were: calf thymus DNA, 3 to 1: DNA from V79 nuclei, 8 to 1; DNA from intact V79 cells, 11 to 1. Similar several-fold increases in the proportion of anti-B[a]PDE-DNA adducts in V79 cells over those in calf thymus DNA were observed for a dose range of 1-10 micrograms B[a]P per ml. The relative extent of binding of the activated metabolite of 9-OH-B[a]P to DNA was also much lower in intact V79 cells than in calf thymus DNA after exposure to 9-OH-B[a]P in the presence of the S9 activation system. These results demonstrate that the relative abilities of various reactive benzo[a]pyrene metabolites formed by an exogenous activation system to reach cellular DNA differ substantially. Therefore, assessment of the biological activity of hydrocarbons in mutation assays using exogenous activation systems must take into account not only the amounts of different reactive hydrocarbon metabolites formed but also the relative abilities of these metabolites to reach the DNA of the target cell.

Animals↗
PubMed1987

Pyridine prevents the clastogenicity of benzene but not of benzo[a]pyrene or cyclophosphamide.

Pyridine has been shown to be a much more potent inhibitor than other solvents of the metabolism and therefore the clastogenicity of benzene. In this report, pyridine prevented benzene-derived micronucleus formation in the bone marrow of ICR Swiss mice at much lower levels than xylene did. Time-course experiments did not indicate any delay in the peak micronucleus response to benzene caused by either pyridine or xylene. Similar experiments using pyridine with benzo[a]pyrene and pyridine with cyclophosphamide indicated that the effect of pyridine was specific for benzene. Benzo[a]pyrene (150 mg/kg) was inhibited by pyridine only at levels of 100 mg/kg or more, compared to inhibition of benzene (440 or 880 mg/kg) by pyridine at levels of 5 mg/kg. Cyclophosphamide was not inhibited at any level, and micronucleus formation was increased at lower ratios of pyridine to cyclophosphamide. These results provide indirect conformation of the work by others indicating that benzene is activated in part by a cytochrome P450 isozyme different from those activating benzo[a] pyrene or cyclophosphamide. Since DBA/2 mice (AHH-non-inducible) are more sensitive to benzene than C57Bl/6 mice (AHH-inducible), single and multiple treatments with benzene were compared by micronucleus response in these two strains. DBA mice were more responsive in all cases. Pretreatment with methylcholanthrene caused a greater response to benzene in DBA/2 mice, suggesting that the cytochrome P450 isozyme involved is one of the forms induced by methylcholanthrene independent of the high-affinity Ah receptor. It is hypothesized that more efficient activation of benzene by the unique cytochrome P450 isozyme, perhaps combined with relatively less conjugation, may result in a greater sensitivity of the bone marrow versus the liver, and of DBA/2 versus C57Bl/6 mice.

Animals↗
PubMed1980

Incorporation of exogenous pyrene-labeled histone into Physarum chromatin: a system for studying changes in nucleosomes assembled in vivo.

Treatment of Physarum histone with iodoacetoxypyrene selectively derivatizes a single H3 cysteine with acetoxypyrene. Microplasmodia can incorporate this AP-H3 into nucleosomes. The distinction between blue monomeric pyrene fluorescence and green excimer pyrene fluorescence allows detection of changes in distance between the closely positioned H3 cysteines in nucleosomes. Fluorescence of nucleosomes labeled in vivo with AP-H3 is almost exclusively of the excimer form, indicating that H3 cysteines are within a few angstroms of each other in the nucleosome core. In histones recovered from these nucleosomes all detectable pyrene is covalently bound to H3. When Physarum is exposed sequentially to labeled followed by unlabeled histone, there is a rapid appearance of green excimer emission in nucleosomes after addition of labeled histone and no apparent switch from excimer to monomer fluorescence after several replications of the genome in the presence of unlabeled histone. These experiments provide evidence in favor of a model for conservative distribution of nucleosomal histones during chromatin replication.

Biological Transport↗
PubMed1988

Interaction of S-100b protein with cardiolipin vesicles as monitored by electron spin resonance, pyrene fluorescence and circular dichroism.

The interaction of S-100b protein with cardiolipin (CL) vesicles has been studied by electron spin resonance, pyrene fluorescence, and circular dichroism. Electron spin resonance and pyrene fluorescence data indicate that S-100b binds to the polar surface of vesicles Ca2+-independently. In the presence of Ca2+, S-100b potentiates the Ca2+-induced clustering of the polar headgroups of CL molecules and causes a further reduction in the Ca2+-dependent decrease in the lateral mobility of the pyrene inserted into the lipid bilayer, which points to an effect of the protein on the hydrophobic core of the lipid bilayer through a larger perturbation of its polar surface. Circular dichroism analyses indicate that CL vesicles cause a decrease in the alpha-helical content of S-100b, analogous to that produced by Ca2+ and that the effects of CL vesicles and of Ca2+ on the secondary structure of the protein are supra-additive. By this technique, we found that the affinity of Ca2+ for S-100b increases substantially in the presence of CL vesicles, even in the presence of physiologic concentrations of KCl, suggesting that once S-100b had interacted with CL vesicles it assumes a new conformation in which its Ca2+-binding properties are greatly enhanced. These results are discussed in relation to binding of S-100b proteins to natural membranes, and to a possible involvement of S-100b in the regulation of membrane structural organization.

Calcium↗
PubMed1987

Early changes in T lymphocytes and subsets of mouse progeny defective as adults in controlling growth of a syngeneic tumor after in utero insult with benzo(a)pyrene.

Benzo(a)pyrene, a potent carcinogen, severely suppresses the anti-SRBC plaque-forming cell response, the mixed lymphocyte response (afferent T cell function), and an in vivo graft-vs.-host response (efferent T cell function) of mouse progeny exposed to the carcinogen during gestation (11 to 13 days). Immunodeficiency occurs early after birth (1 week) and persists for 18 months. The abnormalities in the T cell-mediated responses led us to examine the quantitative profile of T cells and subsets (Lyt 1+, Lyt 2+) present in the lymphoid organs during fetogenesis (15 to 19 days) and postnatally. In addition, we examined the ability of 3- to 8-month-old progeny and their spleen cells to resist the in vivo growth of cells from a syngeneic fibrosarcoma (a tumor that had been induced by benzo(a)pyrene). Our observations included: (1) Depletion of T cells and subsets in the thymus late (19 days) in gestation and postnatally. (2) Depleted T and Lyt 1+ cells in the spleen during gestation, while postnatally the former were enhanced and the effect on the latter was variable (enhancement and reduction). (3) In the fetal liver, the T cells were reduced, but the Lyt 1+ cells were unchanged. (4) The Lyt 2+ cells were strikingly enhanced in the fetal liver and spleen, but most dramatically for the former. (5) The Lyt 1/Lyt 2 ratio was less than 1.00 or controls in the fetal liver and spleen, a condition which persisted for 30 days postnatally in the latter organ. (6) Benzo(a)pyrene-exposed progeny or their spleen cells were relatively ineffective in resisting in vivo growth of transferred tumor cells. These results show that this carcinogenic pollutant induces a marked disorientation of T cells and subsets which can persist for at least 4 weeks postnatally. This suggests disruption of T cell differentiation during ontogenesis which may have profound implications on the ability to resist induction and growth of neoplasias after in utero exposure to the carcinogen.

Animals↗
PubMed1986

Mutagenicity of the photochemical reaction products of pyrene with nitrogen dioxide.

The mutagenicity of the photochemical reaction products of pyrene with nitrogen dioxide (NO2) and the mutagens in them were investigated for the interpretation of their biological significance as genetoxic hazards of polycyclic aromatic hydrocarbons (PAHs) in airborne particles. Samples extracted from the photochemical reaction products of pyrene with NO2 diluted with air using a high-pressure mercury lamp were mutagenic for Salmonella typhimurium strains TA97 and TA98 in the absence of S9 mix, with a trend to detoxification in the presence of the metabolic system. The mutagens in the crude samples extracted from their products, which were fractionated by normal-phase high-performance liquid chromatography (HPLC) on a column of Nucleosil 100-30 with n-hexane-benzene as an eluting solution, were analyzed by HPLC, mass spectrometry and Fourier transform infrared (FT-IR) spectrometry. Based on these results, it was recognized that 1-nitropyrene (1-NP), 1,3-dinitropyrene (1,3-DNP), 1,6-dinitropyrene (1,6-DNP) and 1,8-dinitropyrene (1,8-DNP) was formed by the photochemical reaction of pyrene with NO2. The yield of DNPs peaked at 2-3 h irradiation.

Chromatography, High Pressure Liquid↗
PubMed1991

Low absolute mutagenic efficiency but high cytotoxicity of a non-bay region diol epoxide derived from benzo[a]pyrene.

Insights into the mechanisms of chemical carcinogenesis can sometimes be gained by comparing the effects of closely related chemicals which differ in carcinogenic potency. We have treated Chinese hamster ovary (CHO) cells with a non-carcinogenic metabolite of benzo[a]pyrene, 9r,10t-dihydroxy-7c,8c-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE-III), and measured the formation and persistence of DNA adducts. We have correlated this binding data with cytotoxicity and mutagenicity in a DNA-repair-proficient CHO cell line (AT3-2) and in two derived lines, UVL-1 and UVL-10, which are unable to repair bulky DNA adducts. These data are compared with similar studies of the effects of the carcinogenic metabolite, 7r,8t-dihydroxy-9t,10t-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE-I). Synchronous fluorescence spectroscopy was used to measure the levels of BPDE-III-DNA adducts in treated cells. Adduct levels increased linearly with dose, but the absolute binding levels were about 30-fold lower than in comparable incubations with BPDE-I. Measurements of the removal of adducts derived from these two diol epoxides indicated no significant difference in the rate of repair measured 24 h post-treatment. When cells were treated with increasing doses of BPDE-III, survival curves were obtained which exhibited a shoulder region at low doses and an exponential decrease in plating efficiency at higher doses. By comparison of the D0's, the DNA-repair-deficient cell lines were found to be 4-5-fold more sensitive to the killing effects of BPDE-III than were the repair-proficient AT3-2 cells.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1991

Genotoxicity of pyrene oxide and 1-nitropyrene oxides in hepatocyte primary culture/DNA repair test.

The genotoxicity of a pyrene oxide, 1-nitropyrene (NP) oxides and other related compounds was examined in the hepatocyte primary culture (HPC)/DNA repair test. Pyrene 4,5-oxide and both 1-NP-4,5-oxide and 1-NP-9,10-oxide elicited clearly positive responses of DNA repair. In this assay, 1-NP itself was weakly positive. However, other related chemicals such as pyrene, 1-nitro-3-hydroxypyrene, 1-nitro-6-hydroxypyrene, and 1-nitro-8-hydroxypyrene did not generate positive responses.

Animals↗
PubMed1991

In vivo benzo[a]pyrene diol epoxide-induced alkali-labile sites are not apurinic sites.

We have used endonuclease IV from Escherichia coli as a probe for apurinic sites in the DNA of HeLa cells following treatment with an activated diol epoxide derivative of benzo[a]pyrene. DNA strand breaks and alkali-labile sites were observed that were repaired following exposure to the carcinogenic alkylating agent. The alkali-labile sites were not substrates for the apurinic site-specific endonuclease IV. We conclude that the alkali-labile sites formed in vivo by benzo[a]pyrene derivatives are not apurinic sites and probably arise as a consequence of rearrangement of the abundant N2-guanine adducts. This finding questions the involvement of apurinic sites in the mutagenic activity of benzo[a]pyrene.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1983

Strand-break formation in DNA modified by benzo[alpha]pyrene diolepoxide. Quantitative cleavage by Escherichia coli uvrABC endonuclease.

Covalently closed circular plasmid DNA was modified by benzo[alpha]pyrene diolepoxide and incubated with partially purified fractions of the Escherichia coli uvr+ gene products. Strand breaks were introduced into the modified DNA by the uvrABC endonuclease; on average, one break was formed for each bound benzo[alpha]pyrene residue in the DNA. These results are direct evidence that benzo[alpha]pyrene adducts in DNA are acted upon by the same repair enzyme as those that handle UV-induced lesions in DNA.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1985

Inhibition by plant phenols of benzo[a]pyrene-induced nuclear aberrations in mammalian intestinal cells: a rapid in vivo assessment method.

The polycyclic aromatic hydrocarbon, benzo[a]pyrene, induced dose-related nuclear damage (micronuclei, pyknotic nuclei and karyorrhectic bodies) in colonic epithelial cells of C57BL/6J mice within 24 hr when administered intrarectally in single doses of 0-200 mg/kg body weight. This damage was reduced when mice ingested the plant phenols, caffeic, ferulic and ellagic acids, and quercetin at levels of 4% or BHA at 2% (w/w) in the diet for 1 wk prior to the benzo[a]pyrene challenge (100 mg/kg body weight). Benzo[a]pyrene-induced nuclear damage was not significantly inhibited by 4% curcumin under similar conditions. The inhibition of nuclear damage is consistent with reported antimutagenic effects for these agents in vitro and in longer term animal studies. The procedure described here may provide a rapid in vivo method for assessing the potential of natural products to inhibit the carcinogenic process.

Animals↗
PubMed1991

Alterations of pulmonary benzo[a]pyrene metabolism by reactive oxygen metabolites.

Superoxide anion radical and hydrogen peroxide (H2O2) are reactive oxygen metabolites which are thought to be involved in oxidant-induced lung injuries. Therefore, we studied their effects on the pulmonary metabolism of benzo[a]pyrene (BP) in rat lung microsomes. The microsomes were incubated with xanthine and xanthine oxidase to generate superoxide anion (effects verified with superoxide dismutase) or H2O2 and then the products formed during the metabolism of BP were measured. Both oxygen metabolites inhibit BP hydroxylase activity, i.e., the production of 3- and 9-hydroxybenzo[a]pyrene (phenols) in a concentration-dependent manner. The phenols account for approximately 75% of metabolite formation and are the major products of BP metabolism. Two components of the monooxygenase system responsible for BP metabolism, cytochrome P-450 and NADPH-cytochrome P-450 reductase, are also inhibited by the two oxygen metabolites in a similar manner. Superoxide anion is more effective than H2O2 in the inhibition of both BP hydroxylase and the monooxygenase components. Neither oxygen metabolite has any effect on the formation of minor metabolites of benzo[a]pyrene, i.e., BP-quinones and BP-dihydrodiols. These are the BP metabolites thought to produce toxic effects and which may lead to the formation of carcinogens and/or mutagens. The results of all these experiments suggest that exposure of lung microsomes to oxygen metabolites can lead to a slowing of overall BP metabolism and the increased accumulation of potentially toxic BP metabolites.

Animals↗
PubMed1982

Fluorescence spectroscopic studies of pyrene-actin adducts.

Reaction kinetic studies of the sulfhydryl-directed fluorescent probes N-(1-pyrene)maleimide (PM) and N-(1-pyrenyl)iodoacetamide with actin from rabbit skeletal muscle showed that there were three accessible sulfhydryl groups in actin. Fluorescence spectral studies showed energy transfer from aromatic amino acid residues to fluorophore reacted at Cys-373, as well as weak excimer fluorescence probably due to doubly labeled molecules at Cys-10 and Cys-373. These results provide further evidence that trytophan and tyrosine residues are located near the probe attached to Cys-373 or Cys-10 and the latter two thiols are in close proximity. In age PM-labeled F-actin, the succinimido ring of PM underwent intramolecular aminolysis, resulting in large emission spectral changes and increased excimer fluorescence. Solvent perturbation studies indicate that the probes were located in a hydrophobic environment; their quantum yield and spectrum properties were very sensitive to changes in the microenvironment. Nanosecond-pulse fluorimetry studies revealed complex fluorescence emission decays with three intrinsic lifetimes in adducts with low molecular weight thiols as well as in labeled proteins. Fluorescence lifetimes were 17, 48 and 111 ns for the pyrenemaleimide adduct of actin, and 3, 14 and 60 ns for the pyrenyliodoacetamide adduct. Supporting evidence is given for the argument that multiple fluorescence lifetimes are an intrinsic property of the pyrene derivatives and are not due to the presence of impurity or heterogeneity in the protein reaction sites. Because of their high sensitivity and long lifetimes, pyrene derivatives are extremely useful.

Actins↗
PubMed1993

The interaction of pyrene labeled diacylglycerol with protein kinase C in mixed micelles.

The binding of protein kinase C (PKC) to pyrene-labeled diacylglycerol (pDG) has been studied in a mixed micellar system by monitoring resonance energy transfer from excited tryptophans to pyrene with time-correlated single photon counting. The average lifetime of the excited state of the tryptophans in PKC showed a clear dependence on the mole percentage pDG in micelles in contrast with pyrene-labeled phosphatidylcholine (pPC). The binding data has been analyzed to a simple model which encompasses the size of the micelles and the binding constant of the pDG-PKC complex. From our data, though, these quantities cannot be determined independently. If we have no size information on the micelles we can determine a lower boundary of this quantity compatible with the data. When the micellar size is known, a binding constant for the DG-PKC complex can be extracted. The presented analytical approach can be applied to other systems in which lipid-protein interactions must be quantified.

Animals↗
PubMed1981

Removal of benzo[a]pyrene from cells by various components of medium.

Benzo[a]pyrene is removed from cells in culture by various additions to the medium. During post-treatment incubation, WI-38 fibroblasts were incubated with a low density, very low density and high density lipoproteins, delipidated or complete serum or plasma, or serum albumin. The time course of removal was followed. Increasing concentrations of lipoproteins resulted in increasing percentages of removal of benzo[a]pyrene from cell membranes. The most efficient addition was 10% complete human plasma. These results indicate that benzo[a]pyrene remains at or close to the plasma membrane for at least several hours and readily redistributes to medium components.

Benzo(a)pyrene↗
PubMed1984

Enzyme immunoassay of benzo[a]pyrene conjugated to DNA, RNA and microsomal proteins using a monoclonal antibody.

An enzyme immunoassay for the detection of benzo[a]pyrene covalently conjugated to macromolecules has been developed. The monoclonal antibody, raised through in vitro immunization reacted with benzo[a]pyrene metabolites bound to DNA, RNA and proteins. The lower detection limit for the assay was 1 pmol for benzo[a]pyrene bound to DNA or RNA, and 5 pmol when bound to protein.

Animals↗