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PubMed1977

Carcinogenicity of benzo-ring derivatives of benzo(a)pyrene on mouse skin.

Benzo(a)pyrene (BP) and several benzo-ring derivatives of BP were tested for carcinogenic activity in mice by topical application of each compound once every 2 weeks for 60 weeks. Chronic treatment of C57BL/6J mice with (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (0.025 to 0.10 micronmole/application) indicated that the dihydrodiol was slightly more active as a complete carcinogen than the parent hydrocarbon BP. 7,8-Dihydroxy-7,8,9,10-tetrahydro-benzo(a)pyrene, a compound related to (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene but which lacks the double bond at position 9,10, was inactive as a carcinogen on mouse skin. These results indicate the importance of the double bond at position 9,10 for the carcinogenic activity of (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene. Chronic treatment of mice with -.4 micronmole of the highly mutagenic (+/-)-7,beta,8alpha-dihydroxy-9alpha, 10alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, (+/-)-7beta,8alpha-dihydroxy-9beta, 10beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, or 9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene every 2 weeks for 60 weeks resulted in tumor incidences of 0, 8, and 4%, respectively, whereas BP at this dose caused a 100% tumor incidence. The high reactivity of the three epoxides may account for their inactivity or their weak carcinogenic activity on mouse skin.

Animals↗
PubMed1992

Distribution to the fetus and major organs of the rat following inhalation exposure to pyrene.

Concentrations of pyrene and total metabolites were determined for individual fetuses and selected maternal organs and tissues immediately and 6 h following a 95-min head-only exposure of pregnant Wistar rats, on gestation day 17, to five levels of pyrene over the range 200-800 mg m-3 as a microcondensation aerosol. The influence of uterine horn, side and position, on distribution to the fetus was assessed. The concentration of both pyrene and its metabolites increased more over the exposure range (eightfold) than did those in the fetus. Concentrations of pyrene or its metabolites in fetal tissues were not found to be related to its position on the uterine horn. There was an unexplained and significant (P less than 0.01) higher concentration of pyrene in fetuses on the right side relative to the left side of the uterine horn for the animals killed immediately following exposure. A comparison of the levels in maternal tissues measured immediately following the exposure and 6 h later showed that there was some redistribution of pyrene and its metabolites to the fat tissues, i.e. levels in the fat increased over the 6 h period following the exposure. Levels in the other tissues diminished during this period. In general, concentrations of pyrene and its metabolites were lowest in the fetal tissues relative to those in the sampled maternal organs and tissues.

Administration, Inhalation↗
PubMed1990

Diethylstilbestrol potentiates and testosterone antagonizes the action of 3-methylcholanthrene on benzo(a)pyrene metabolism in Hep G2 cells.

We have used the human hepatoma cell line, Hep G2, to examine the ability of hormones and xenobiotics to modulate the hepatic induction of benzo(a)pyrene hydroxylase and epoxide hydrolase. Hep G2 cells were cultured in Eagle's Minimum Essential Medium supplemented with 10% fetal calf serum. 3-Methylcholanthrene, diethylstilbestrol, testosterone propionate, and combinations of 3-methylcholanthrene, and each of the hormones were added directly to the culture media. We subsequently studied the metabolism of benzo(a)pyrene using cell lysates of the Hep G2 cells. Metabolites were quantitated by high-performance liquid chromatography (HPLC) using fluorodetection. Exposure to 3-methylcholanthrene alone resulted in an eightfold increase in total benzo(a)pyrene metabolites with a change of the predominant metabolite from the 3-hydroxybenzo(a)pyrene to the carcinogenic pathway of the benzo(a)pyrene-7,8-diol. Diethylstilbestrol and testosterone propionate resulted in small, but significant, decreases in metabolism of benzo(a)pyrene. When exposed in combination with 3-methylcholanthrene, testosterone propionate antagonized and diethylstilbestrol potentiated the metabolism of benzo(a)pyrene. 3-Methylcholanthrene, diethylstilbestrol, and combinations of 3-methylcholanthrene and diethylstilbestrol or testosterone propionate resulted in increased epoxide hydrolase activity as compared to controls. These results, carried out in a human hepatoma cell line, lend support to a concern for potentiated toxicity and carcinogenicity following exposure to complex chemical mixtures.

Benzo(a)pyrene↗
PubMed1992

Modulation of aortic protein phosphorylation by benzo(a)pyrene: implications in PAH-induced atherogenesis.

The toxicity of polycyclic aromatic hydrocarbons such as benzo(a)pyrene, 7,12-dimethylbenz(a)anthracene, and 3-methylcholanthrene has been associated with alterations in the proliferation of vascular smooth muscle cells and the development of lesions of mesenchymal origin. Because phosphorylation of endogenous substrates plays a central role in the regulation of smooth muscle cell growth, the present studies were conducted to evaluate the phosphorylation pattern of medial aortic protein upon repeated in vivo exposure of Japanese quail to benzo(a)pyrene (BaP). Medial aortic homogenates from quail treated for 10 weeks with 10 mg/kg benzo(a)pyrene or vehicle were processed for in vitro measurements of protein phosphorylation. In vitro phosphorylation of endogenous or exogenous proteins stimulated in vitro by phorbol myristate acetate/phosphatidylserine or cyclic AMP, known activators of protein kinase C and cyclic AMP-dependent protein kinase, respectively, was examined in the cytosolic and particulate fractions of homogenates from control and treated animals. Benzo(a)pyrene treatment significantly enhanced the basal phosphorylation of M(r) 113, 35, and 23 kDa proteins in the cytosolic fraction. Modest increases in the phosphorylation of M(r) 71, 52, and 38 kDa were also observed under basal conditions. No changes in the basal phosphorylation of particulate proteins were observed. Phosphorylation of endogenous protein substrates by protein kinase C in the cytosolic fraction was not altered by benzo(a)pyrene treatment. In contrast, inhibition of C-kinase-mediated phosphorylation of endogenous M(r) 272, 72, and 45 kDa proteins was observed in the particulate fraction of aortic homogenates from benzo(a)pyrene-treated quail relative to controls. Exogenous histone phosphorylation by PKC in the particulate, but not cytosolic fraction, was decreased by benzo(a)pyrene treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1999

Effects of solvent on DNA adduct formation in skin and lung of CD1 mice exposed cutaneously to benzo(a)pyrene.

The effect of solvent polarity and lipophilicity on DNA adduct formation by polycyclic aromatic hydrocarbons in skin and lung has been studied in CD1 mice exposed cutaneously in vivo to benzo(a)pyrene ( approximately 0.01-7.0 microg/animal) in either tetrahydrofuran or n-dodecane. The nature and amounts of DNA adducts, measured as 7R,8S, 9R-trihydroxy-10S-(N(2)-deoxyguanosyl-3'-phosphate)-7,8,9, 10-tetrahydrobenzo(a)pyrene, in relation to exposure dose and treatment regime was determined by (32)P-postlabelling. In skin DNA there was a linear relationship between exposure dose and adduct formation with both solvents, though the amount of adduct formed was significantly lower from treatment with benzo(a)pyrene in n-dodecane than in tetrahydrofuran. The amounts of adducts measured in skin DNA ranged from 67 amol adducts/microg DNA at the lowest exposure dose of benzo(a)pyrene in n-dodecane to 3.5 fmol adducts/microg DNA (1 adduct in 5 x 10(7) nucleotides to 1 adduct in 9 x 10(5) nucleotides) at the highest dose. In tetrahydrofuran the corresponding levels were 89 amol adducts/microg DNA (1 adduct in 3 x 10(7) nucleotides) to 16.9 fmol adducts/microg DNA (1 adduct in 2 x 10(5) nucleotides). DNA adducts could not be detected in lung tissue following cutaneous treatment of animals with benzo(a)pyrene in n-dodecane. Cutaneous treatment of animals with benzo(a)pyrene in tetrahydrofuran, however, resulted in adducts in lung DNA at a level of 88 amol/microg DNA from exposures only at the highest dose (6.72 microg/animal). The difference in octanol-water partition coefficient, log P(ow) between n-dodecane compared to tetrahydrofuran is considered to be the most likely reason for the reduction in the bioavailability of benzo(a)pyrene and/or its metabolites and hence the degree of genotoxicity in tissues. The results suggest that other paraffinic hydrocarbon solvents may moderate the genotoxicity of polycyclic aromatic hydrocarbons in vivo. The assessment of the genotoxicity in vivo of mixtures of compounds should be carried out on complete mixtures of substances of interest in order to take account of these possible antagonistic or synergistic effects.

Administration, Topical↗
PubMed2002

Effect of pyrene on hepatic cytochrome P450 1A (CYP1A) expression in Nile Tilapia (Oreochromis niloticus).

The effect of pyrene on the regulation of the gene expression of cytochrome P4501A ( CYP1A) was studied in tilapia (Oreochromis niloticus), a tropical fish of great ecological and economical importance. To evaluate CYP1A mRNA, tilapia CYP1A cDNA was cloned, sequenced, and compared with those CYP1A reported sequences in the GeneBank DNA database. The top seven matches corresponded to CYP1A from other teleosts. Hepatic CYP1A mRNA levels showed a significant increase at day 1 after pyrene injection (20 mg kg(-1) body weight [BW]), and this CYP1A mRNA levels did not return to basal levels for up to 5 days. The immunoblot analysis of CYP1A protein levels using polyclonal rabbit-anti-trout antibodies in the liver of pyrene-treated (20 mg kg(-1) BW) tilapias showed a 1.9-fold increase at day 3 after injection. Ethoxyresorufin- O-deethylase (EROD) activity increased 18-fold with respect to control fish at day 3 after injection. CYP1A protein and EROD activity remained increased for 5 days after a single pyrene IP administration. Similarly, the highest concentration of 1-hydroxypyrene (1-OH pyrene) in bile was observed in fish sacrificed at day 3 after injection. EROD activity and 1-OH pyrene concentration showed a statistically significant correlation (r = 0.85) according to the Spearman test, suggesting the participation of this cytochrome in the biotransformation of pyrene.

Amino Acid Sequence↗
PubMed1996

Two-step degradation of pyrene by white-rot fungi and soil microorganisms.

The effect of soil microorganisms on mineralization of 14C-labelled pyrene by white-rot fungi in solid-state fermentation was investigated. Two strains of white-rot fungi, Dichomitus squalens and a Pleurotus sp., were tested. The fungi were incubated on milled wheat straw contaminated with [14C]pyrene for 15 weeks. CO2 and 14CO2 liberated from the cultures were determined weekly. To study the effect of soil microorganisms on respiration and [14C]pyrene mineralization in different periods of fungal development, the fungal substrate was covered with soil at different times of incubation (after 0, 1, 3, 5, 7, 9 or 11 weeks). The two fungi showed contrasting ecological behaviour in competition with the soil microflora. Pleurotus sp. was highly resistant to microbial attack and had the ability to penetrate the soil. D. squalens was less competitive and did not colonize the soil. The resistance of the fungus was dependent on the duration of fungal preincubation. Mineralization of [14C]pyrene by mixed cultures of D. squalens and soil microorganisms was higher than by the fungus or the soil microflora alone when soil was added after 3 weeks of incubation or later. With Pleurotus sp., the mineralization of [14C]pyrene was enhanced by the soil microflora irrespective of the time of soil application. With D. squalens, which in pure culture mineralized less [14C]pyrene than did Pleurotus sp., the increase of [14C]pyrene mineralization caused by soil application was higher than with Pleurotus sp.

Antibiosis↗
PubMed2001

Pyrene degradation by two fungi in a freshwater sediment and evaluation of fungal biomass by ergosterol content.

Mucor racemosus var. sphaerosporus and Phialophora alba were investigated for their abilities to degrade pyrene in a freshwater sediment, with or without glucose supply as nutrient or carbon source, during 90 days. The ergosterol contents in sediment were quantified to estimate fungal biomass and to assess the correlation between fungal activity and biodegradation of pyrene. Results showed that, in an heterogeneous environment, these fungi presented different abilities to degrade pyrene. P. alba increased the degree of pyrene degradation by 9%, compared to the native micro-organisms, but a supply of glucose acted as an inhibitor to pyrene disappearance. M. racemosus var. sphaerosporus was not efficient at sediment bioremediation (with or without glucose added), because it reduced the rate of pyrene degradation by the native microflora. In any case, there was no increase of ergosterol in boxes during bioremediation experiments. In our experimental conditions, ergosterol content could not be correlated to pyrene degradation.

Biodegradation, Environmental↗
PubMed1988

Fluorescence from pyrene-labeled native and reconstituted chicken gizzard tropomyosins.

Sulfhydryl groups at Cys-36 on the beta chain and at Cys-190 on the gamma chain of chicken gizzard tropomyosin were reacted with the pyrene-containing sulfhydryl-specific reagents N-(1-pyrenyl)iodoacetamide and N-(1-pyrenyl)maleimide. Tropomyosin prepared and labeled under nondenaturing conditions displayed significant pyrene monomer emission but low levels of pyrene excimer fluorescence. In contrast, tropomyosin subjected to denaturation and renaturation prior to labeling, or labeled in the denatured state prior to renaturation, displayed considerable excimer emission. Furthermore, labeling of isolated beta or gamma chains in denaturant, followed by reconstitution, gave separate samples of beta beta- and gamma gamma-tropomyosin that exhibited even greater pyrene excimer to monomer emission ratios. As pyrene excimers can form only when an excited pyrene is immediately adjacent to a ground state pyrene, i.e., when the labeled Cys residues on the two chains in a tropomyosin coiled coil share the same cross section, these results support conclusions based upon chemical crosslinking studies [C. Sanders, L. D. Burtnick, and L. B. Smillie (1986) J. Biol. Chem. 261, 12774-12778] that native gizzard tropomyosin exists predominantly as a beta gamma-heterodimer. In addition, the low degree of labeling of native gizzard tropomyosin and the differences in degrees of labeling of beta beta- and gamma gamma-tropomyosins in the absence of denaturants reflect on the accessibilities of the sulfhydryl groups in these tropomyosin isoforms. Circular dichroism measurements indicate that the labeled proteins form stable coiled coil structures that have thermal stabilities comparable to that of the native protein.

Affinity Labels↗
PubMed1986

Evidence that pyrene excimer formation in membranes is not diffusion-controlled.

Kinetic and steady-state measurements of pyrene fluorescence in a variety of model membranes are evaluated in terms of the theory of collisional excimer formation. In the region of 10(-3)-0.1 M pyrene, molecular fluorescence decay in membranes is biphasic and the two component lifetimes do not depend on the pyrene concentration. The lifetime data are consistent with the rate constant for collisional excimer formation being of the order 10(6) M-1 X s-1 or less. The concentration dependence of the component amplitudes is inconsistent with the theory of collisional excimer formation and suggests that pyrene exists in two forms in membranes: a slowly diffusing monomeric form and an aggregated form. The component of molecular fluorescence decay associated with aggregated pyrene is highly correlated with steady-state excimer fluorescence, suggesting that excimer fluorescence in membranes arises from aggregated pyrene in which excimers are formed by a static rather than a collisional mechanism. It is suggested that the concentration dependence of excimer to molecular fluorescence intensity ratios in membranes is related to the equilibrium constant for exchange between monomeric and aggregated pyrene forms rather than to the collisional excimer formation rate constant.

Chloroplasts↗
PubMed1991

Pyrene derivatives as markers of transbilayer effect of lipid peroxidation on neuronal membranes.

Two different pyrene derivatives, namely 12-(1-pyrene)dodecanoic acid (P12-FA) and N-(12-(1-pyrene)dodecanoyl)-galactosylsphingosine I3-sulfate (P12-CS) have been used to follow lipid peroxidation both in model and natural membranes. The malondialdehyde (MDA) production in small unilamellar vesicles of dipalmitoylphosphatidylcholine/arachidonic acid (80:20, molar ratio), symmetrically labelled with both probes determined a progressive decrease of pyrene fluorescence due to an involvement of pyrene in the peroxidative reaction. Nervous membranes are particularly sensitive to lipid oxidation which differentially acts on the two layers of the membrane determining a greater rigidity of the exofacial one. Thus, we consider the possibility to asymmetrically introduce the pyrene ring, as P12-FA or P12-CS, in synaptosomes for monitoring lipid peroxidation in each layer of the membrane. The amount of the two probes incorporated in the membrane was 20 +/- 3 and 10 +/- 2 nmol/mg of protein for P12-FA and P12-CS, respectively. P12-FA was symmetrically distributed in the two layers, whereas 95% of P12-CS was incorporated in the exofacial layer of the membrane as determined by TNBS measurements. The decrease in fluorescence of synaptosome associated pyrene was, in the early stages of lipid peroxidation, greater for P12-CS than for P12-FA labelled membranes, indicating a greater susceptibility of the exofacial layer to iron-induced peroxidation.

Animals↗
PubMed1991

Administration of pyrene lipids by receptor-mediated endocytosis and their degradation in skin fibroblasts.

Sphingomyelin and seven glycosphingolipids were labeled with the fluorescent probe pyrene and administered into cultured fibroblasts by receptor-mediated endocytosis. For this purpose pyrene sphingomyelin or mixtures of pyrene glycolipid and unlabeled sphingomyelin were dispersed as small, unilamellar liposomes. Apolipoprotein E was then added and the receptor for this ligand on the cell surface was utilized for uptake of the liposomes and their transport to the lysosomes, where the respective pyrene lipids were degraded. Following incubation with each of the respective pyrene lipids, only the administered compound and the pyrene ceramide were present; intermediate hydrolysis products were not detected. This indicated that, in skin fibroblasts, the lysosomal ceramidase was limiting and controlled the rate of total degradation of the pyrene sphingolipids.

Apolipoproteins E↗
PubMed1985

Toxicity of polycyclic aromatic hydrocarbons. I. Effect of phenanthrene, pyrene, and their ozonized products on blood chemistry in rats.

Male Sprague-Dawley rats were treated with a single ip injection of physiological saline (3.0 ml/kg), dimethyl sulfoxide (DMSO, 3.0 ml/kg), phenanthrene (150 mg/kg), ozonized products of phenanthrene (150 mg/kg), pyrene (150 mg/kg), or ozonized products of pyrene (150 mg/kg). Phenanthrene, pyrene, and their ozonized products were dissolved in DMSO (50 mg/ml). Serum aspartate aminotransferase (AST) activity was increased significantly 24 hr after ip administration of DMSO when compared with physiological saline. Phenanthrene produced a significant elevation of serum AST and gamma-glutamyl transpeptidase (GGTP) levels related to physiological saline and DMSO-injected rats 24 hr after injection. However, GGTP levels for groups treated with DMSO or phenanthrene were not significantly increased when compared with saline groups 72 hr after injection. Ozonized products of phenanthrene produced a significant elevation of serum AST, alanine aminotransferase (ALT), GGTP, and bilirubin levels when compared with groups treated with physiological saline, DMSO, and phenanthrene 24 or 72 hr after injections. The ozonized products of phenanthrene also produced significant elevation of serum creatinine levels compared with physiological saline, DMSO, and phenanthrene groups at 24 hr after treatment and of blood urea nitrogen (BUN) levels at 24 and 72 hr. Although pyrene caused a small but significant increase in the serum AST and bilirubin levels 24 hr after treatment, no significant change in the serum AST, ALT, GGTP, BUN, and creatine levels were observed with the ozonized products of pyrene at 24 or 72 hr. This study demonstrates significant alterations in serum chemistry induced by reaction products of ozone with phenanthrene. No such effect was observed when the products of pyrene ozonation were administered. Although the ozonation products of pyrene were not toxic under the conditions of this study, phenanthrene products were more hepatotoxic than was phenanthrene itself. Nephrotoxicity was also an apparent effect of ozonized phenanthrene. Since ozone-polycyclic aromatic hydrocarbon (PAH) reactions may occur in the atmosphere, these reactions might produce compounds that are more toxic than either ozone or the PAH alone.

Alanine Transaminase↗
PubMed1992

Mutagenicity of nitro-azabenzo[a]pyrene and its related compounds.

The mutagenicity of nitrated benzo[a]pyrene (BP) and the related compounds, 1- and 3-nitrobenzo[a]pyrene (NBP), 1- and 3-nitro-6-cyanobenzo[a]pyrene (N-6-CBP), 1- and 3-nitro-6-azabenzo[a]-pyrene (N-6-ABP), 1- and 3-nitro-6-azabenzo[a]-pyrene-N-oxide (N-6-ABPO) and 1,6- and 3,6-dinitrobenzo[a]-pyrene (DNBP), was investigated. The mutagenic activities of 3-N-6-CBP and 3-N-6-ABP were 117 and 76 times, respectively, that of 3-NBP. In addition, 3,6-DNBP was more mutagenic than 1,6-DNBP. It is suggested that the mutagenic activation differs with the position of NO2 substitution in the chemical structure. A nitro derivative with NO2 substitution at the 3 position of the aromatic ring of BP was more mutagenic than that with the substitution at the 1 or 6 position. The reducibility of DNBPs was then determined by detecting 1- or 3-amino-6-nitrobenzo[a]pyrene (A-6-NBP), a metabolite of DNBP; 3,6- and 1,6-DNBP were reduced to 3- and 1-A-6-NBP at frequencies of 958 +/- 26 and 79 +/- 8, respectively, pmole per mg of protein, when the compound was incubated anaerobically with rat liver S9 mix at 37 degrees C for 15 min. NO2 substituted at the 3 position of the aromatic ring of BP was readily reduced by a microsome enzyme to form an amino derivative. The result suggests that these compounds have a structure-activity relationship between mutagenicity and NO2 substitution of BP.

Animals↗
PubMed1983

Cross-linking and fluorescence of pyrene-labeled collagen.

The pyrene-labeling of acid-soluble (type I) and acid-insoluble collagens from young and old rat tail tendon has been investigated. The pyrene excimer fluorescence is associated with stabilized pyrene labels bound to two adjacent aldehydes in monomeric young collagens. Polymeric young collagens, as well as monomeric and polymeric old collagens, tend to lose this specific arrangement. This is shown by salt and new chromatographic fractionation of monomeric and polymeric collagens. During denaturation, pyrene labels are released from saturated aldehydes in both alpha 1 and alpha 2 chains. This unstable pyrene-labeling is stabilized by NaBH4 reduction of the hydrazone bonds between aldehyde groups and pyrene-containing hydrazines. This stabilization reveals that alpha 1 contains more aldehyde groups than does alpha 2 in young collagen. Pepsin-solubilized, acid-insoluble collagens are partly cross-linked and, like acid-soluble collagens, exhibit the fluorescence of pyrene aggregates probably located at unidentified cross-links, different from unsaturated aldehyde-containing cross-links in acid-soluble collagens.

Aging↗
PubMed1985

Pulmonary retention of [14C]benzo[a]pyrene in rats as influenced by the amount instilled.

Studies on the pulmonary retention of benzo[a]pyrene after inhalation have shown that clearance is biphasic, with one component clearing with a half-time greater than 1 day and another with a half-time less than 1 day. In the work reported here we demonstrated that the amount of benzo[a]pyrene instilled in the lungs can affect the rate at which the benzo[a]pyrene is cleared into the blood. Fischer-344 rats were given 16, 90 or 6400 ng of [14C]benzo[a]-pyrene/rat by intratracheal instillation. Rats were sacrificed at various times up to 7 days after instillation. Individual lung lobes and trachea were removed, digested, and analyzed by liquid scintillation spectrometry. At 24 h after instillation the amount of 14C covalently bound to lung macromolecules was determined in some rats. Benzo[a]pyrene equivalents remaining in the lungs was expressed as a percentage of the instilled dose as a function of time. A two-component negative exponential function was fit to the data. With increasing dose (16-6400 ng/rat), an increasing percent (89-99.76%) was cleared with a half-time less than 1 day and a decreasing percent (11.3-0.24%) was cleared with a half-time greater than 1 day, suggesting that the mechanism by which the slower clearances occurred had been saturated at higher doses. At 24 h after instillation, from 1 to 2 pmol of [14C]benzo[a]-pyrene equivalents/lung were covalently bound to lung macromolecules. There was no difference in the amount of covalently bound 14C over the range of instillation doses used, suggesting that a small amount of benzo[a]-pyrene equivalents was bound in the lungs regardless of the amount instilled. These results suggested that linear extrapolation from high dose studies to environmental concentrations might underestimate lung burdens of benzo[a]pyrene.

Animals↗
PubMed1995

Spin relaxation studies of pyrene by 13C nuclear magnetic resonance spectroscopy.

The effect of the repetition and contact times on the intensity of the magic-angle spinning (MAS) spectra of pyrene has been studied. Pyrene, like a great number of fused polyaromatic compounds, has a very large 13C longitudinal relaxation time (T1Z). When using the cross-polarization (CP) MAS technique, the optimum repetition time is 800 s. The simulation of the central line of the pyrene CP-MAS spectra allowed us to determine the chemical shift of each carbon in the solid state. As the T1Z (13C of the total spectrum) of pyrene was observed to be 1780 s, attempts have been made to relax it by the addition of chromium(III) acetylacetonate or by supporting it on a carrier of gamma-Al2O3: the mixing of chromium(III) acetylacetonate to pyrene by solid mixing, or solution mixing followed by evaporation of the solvent, has no effect on its relaxation time; the Haldor Topsøe TK551 catalyst, a gamma-alumina supported Ni-Mo-P catalyst, has been found to be a very efficient spin relaxation agent for the products adsorbed on it. For example, at 25 degrees C, the 10 wt.-% pyrene-TK551 catalyst is 3 x 10(4) times more relaxed than pure pyrene.

Adsorption↗
PubMed1995

Time-resolved microfluorometric study of the binding sites of lipophilic cationic pyrene probes in mitochondria of living HeLa cells.

Lipophilic dye cations specifically bind to the mitochondria of living cells. Using fluorescent dyes, the mitochondria can easily be observed with a fluorescence microscope. Electron microscopy has shown that the dyes are bound to the inner mitochondrial membranes and the cristae. Using time-resolved fluorescence microscopy we have investigated, whether the dye molecules are preferentially accumulated at the strongly hydrophobic protein complexes of energy metabolism or at the lipids of the inner membrane system. In order to use our nanosecond-pulsed laser fluorometer we synthesized specially designed lipophilic pyrene cations with S1 lifetimes in the nanosecond domain, which specifically stain mitochondria in living HeLa cells. Model experiments with artificial membranes such as liposomes, proteoliposomes and also protein complexes have shown that the fluorescence is strongly quenched by oxygen if the pyrene probes are bound to lipids. Binding to proteins causes a much smaller quenching effect. In artificial systems, all decays were single exponential. This is in contrast with incubated HeLa cells, which showed double-exponential fluorescence decays. Comparing these with the artificial systems we came to the conclusion that in HeLa cells the long-lived species 1 are pyrene probes preferentially bound to the proteins of the inner mitochondrial membranes. The short-lived species 2 is caused by fluorescence resonance energy transfer from the pyrene probes as donors to cytochromes of the inner membranes as acceptors. From our decay data we estimated a mean distance between donor and acceptor of about 40 A. This is the same order of magnitude as the mean diameters of several mitochondrial protein complexes. Therefore we assumed that species 2 are pyrene probes bound either to mitochondrial proteins with cytochromes as constituents or to the interface between these proteins and the phospholipids of the membranes. Thus both species 1 and species 2 are spatially related to mitochrondrial proteins. This agrees with the observation that respiration of HeLa cells as well as cytochrome c oxidase vesicles (COVs) are inhibited with increasing concentration of pyrene probes. Finally, we studied the photodynamic effect on irradiation of HeLa cells and of COVs after incubation with lipophilic pyrene and porphyrine cations.

Binding Sites↗