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 1,441 records · Page 80Linked to original sources
PubMed2005

Effect of experimental desynchronosis on immunotoxicity of benz(a)pyrene in (CBAxC57Bl)F1 mice.

Experiments on (CBA x C57Bl)F1 mice showed that constant (day and night) illumination for 2 weeks led to the development of internal desynchronosis, which significantly modulated the reaction of the immune system to benz(a)pyrene compared to those in intact animals. Presumably, the differences were associated with changed circadian rhythms of the immune parameters in experimental animals determining different ratios and, presumably, functions of immunocompetent cells during benz(a)pyrene exposure in intact controls and animals with desynchronosis.

Animals↗
PubMed2005

Effect of benzo[a]pyrene on the immune status of mice with anxious-depressive syndrome.

We studied the effect of benzo[a]pyrene on cells of lymphoid organs, energy metabolism of blood lymphocytes, and immunological reactivity in mice with anxious depressive syndrome produced by social stress. Benzo[a]pyrene exhibited a more pronounced immunotoxic activity in anxious-depressive animals, which was more than a simple sum of the effects produced by adverse ecological and psychic factors.

Animals↗
PubMed2005

Chemopreventive effect of piperine on mitochondrial TCA cycle and phase-I and glutathione-metabolizing enzymes in benzo(a)pyrene induced lung carcinogenesis in Swiss albino mice.

Piperine is a major component of black (Piper nigrum Linn) and long pepper (Piper longum Linn) used widely in various systems of traditional medicine. We have evaluated the effect of piperine on mitochondrial tricarboxylic acid cycle and phase I and glutathione-metabolizing enzymes in Benzo(a)pyrene induced experimental lung carcinogenesis in swiss albino mice. Lung cancer bearing mice showed a significant decrease in the activities of mitochondrial enzymes-isocitrate dehydrogenase (ICDH), -ketoglutarate dehydrogenase (KDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH) and significantly increased NADPH-Cytochorome reductase (NADPH-C reductase), cytochrome P450 (cyt-p450) and cytochrome b5(cyt-b5). The activities of glutathione-metabolizing enzymes glutathione peroxidase(GPx), glutathione reductase (GR) and glucose-6-phospho dehydrogenase(G6PDH) were significantly lowered in lung-cancer bearing mice when compared with control mice. Piperine supplementation to tumour-induced animals significantly lowered the phase-I enzymes (NADPH-C reductase, cyt-p450 and cyt-b5)) and there was a rise in glutathione-metabolizing enzymes (GPx, GR and G6PDH), which indicated an antitumour and anti-cancer effect. Comparison of normal control mice and mice administered piperine only as drug control showed no significant variations in enzyme activities. Piprine administration to benzo(a)pyrene induced animals significantly increased the activities of mitochondrial enzymes, thereby suggesting its role in mitochondrial energy production.

Alkaloids↗
PubMed1986

Quantifying adductive modification of hemoglobin from mice exposed to benzo[a]pyrene.

The present work describes a method for the detection of minute amounts of benzo[a]pyrene, as the diolepoxide metabolite, bound covalently to the hemoglobin of erythrocytes isolated from mice previously exposed to the carcinogen. The technique consists of the acid-induced removal of the pyrenyl moiety from the hemoglobin as the strongly fluorescent free tetrols and their isolation by bonded-phase extraction methods and subsequent quantitation by fluorescence/HPLC. With this procedure as little as 5 pg of tetrol can be detected. The assay was used to determine the amount of benzo[a]pyrene-hemoglobin adduct formation in mice bearing a carcinogen-induced fibrosarcoma.

Animals↗
PubMed1983

Differential metabolism of acetanilide versus ethoxycoumarin and benzo[a]pyrene by two 3-methylcholanthrene-inducible forms of rat liver cytochrome P-450.

The present study compares the catalytic activities of two 3-methylcholanthrene (3-MC) inducible forms of cytochrome P-450. These isozymes (P-448HCB and P-448MC) were isolated from liver microsomes of rats treated with 3,4,5,3',4',5'-hexachlorobiphenyl (HCB) and 3-MC, respectively. Catalytic activities of the isozymes were compared in a reconstituted system and by antibody inhibition studies in microsomes. In a reconstituted system, P-448HCB had very little catalytic activity toward benzo[a]pyrene or ethoxycoumarin (substrates metabolized preferentially by P-448MC). In contrast, both isozymes had high turnover numbers for aniline and acetanilide. However, catalytic activities of the purified isozymes were affected dramatically by Emulgen 911, a nonionic detergent. Since nonionic detergents used in the purification of P-450 isozymes cannot be completely removed after purification, residual amounts of detergent probably affect turnover numbers in a reconstituted system. Therefore, specific antibodies to cytochromes P-448MC and P-448HCB were used to examine the contribution of these isozymes to microsomal metabolism. Antibody inhibition studies confirmed that the majority of benzo[a]pyrene and ethoxycoumarin metabolism in 3-MC-induced microsomes was catalyzed by cytochrome P-448MC. In contrast, P-448HCB accounted for the majority of the acetanilide hydroxylase activity in 3-MC- and HCB-induced microsomes. Neither isozyme contributed appreciably to metabolism of these substrates in control microsomes.

Acetanilides↗
PubMed1989

Synthesis of pyrene derivatives of cerebroside sulfate and their use for determining arylsulfatase A activity.

Two fluorescent derivatives of cerebroside sulfate ('sulfatide') have been synthesized and used as substrates for determining arylsulfatase A activity. These were 12-(1-pyrene)dodecanoyl cerebroside sulfate (P12-sulfatide) and 12(1-pyrenesulfonylamido)dodecanoyl cerebroside sulfate (PSA12-sulfatide). When incubated at pH 5.0 in the presence of 5 mM MnCl2 and 5.5 mM of taurodeoxycholate, either substrate was hydrolyzed by arylsulfatase A of human leukocytes. The rate of hydrolysis was proportional to the incubation time and concentration of enzyme; Michaelis-Menten type kinetics were observed with increasing concentrations of substrate. For determining the rate of hydrolysis, each of the two products (i.e., P12- and PSA12-cerebrosides) were separated from the bulk of respective unreacted sulfatide on small columns of DEAE-Sephadex A-25 and their fluorescence intensities read at 343-378 and 350-380 nm for the excitation and emission wavelengths for P12- and PSA12-cerebrosides, respectively. When extracts of skin fibroblasts derived from normal individuals and patients with Maroteaux-Lamy (lacking arylsulfatase B) or metachromatic leukodystrophy (lacking arylsulfatase A) were used as source of enzyme, P12-sulfatide was hydrolyzed by the former two but not by the latter cell extract. Several derivatives of cerebroside sulfate were also synthesized and found to inhibit the hydrolysis of pyrenesulfatide by leukocyte arylsulfatase A. The results demonstrate that these two pyrene containing sulfatides can be effectively used as specific substrates for the determination of arylsulfatase A activity in extract of cells and most probably also of tissues.

Animals↗
PubMed1976

Fluorescence study of N-(3-pyrene)maleimide conjugated to rabbit skeletal F-actin and plasmodium actin polymers.

A fluorescent probe N-(3-pyrene)maleimide was conjugated to rabbit skeletal F-actin at the site of most reactive sulfhydryl group (Cys-373). Its fluorescence anisotropy decay showed a single correlation time of 560 ns at 25 degrees C, which is in a very good agreement with the correlation time of the dansyl-L-cysteine group conjugated to the same site of F-actin reported very recently [Wahl, Ph., Mihashi, K, and Auchet, J-C. (1975) FEBS Lett. 8, 164-167]. Actin from plasmodia of myxomycates, Physarum polycepharum, was also conjugated with N-(3-pyrene) maleimide and the fluorescence anisotropy was compared with rabbit skeletal F-actin using the classical steady excitation method. It was found that the internal mobility of the magnesium polymer of plasmodium actin is remarkably larger than both plasmodium F-actin and rabbit skeletal F-actin.

Actins↗
PubMed1983

Liposomal uptake of microcrystalline benzo(a)pyrene studied with synchronous fluorescence.

Synchronous fluorescence spectrometry is employed for kinetic studies of benzo(a)pyrene uptake by phospholipid bilayers. It provides several advantages over the conventional mode. These include less background interferences, higher sensitivity, and relatively independent of dynamic quenching by paramagnetic ions. The rate limiting step in benzo(a)pyrene uptake appears to be a first order process not controlled by diffusion. Signal enhancement upon successive increments of liposomes decreases as if it is dependent on the number of free microcrystals in solution.

Benzo(a)pyrene↗
PubMed1984

Conformations of adducts and kinetics of binding to DNA of the optically pure enantiomers of anti-benzo(a)pyrene diol epoxide.

Kinetic flow dichroism studies indicate that the (+) enantiomer of 7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene physically bound at intercalative-type sites in double-stranded DNA undergoes covalent binding reactions to form adducts at external binding sites. The conformation of the non-covalent complex derived from the (-) stereoisomer is also intercalative in nature, but the conformations of the covalent adducts are heterogeneous and are characterized by both intercalative-type and external conformations. It is suggested that the distinctly higher biological activity of the (+) enantiomer relative to the activity of the (-) enantiomer may be related to the preponderance of 7,8,9-triol benzo(a)pyrene residues covalently linked to deoxyguanine and located at external binding sites in the DNA adducts.

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

Involvement of cytochrome b5 in the hepatic microsomal metabolism of benzo(a)pyrene.

Ethanol consumption decreased the specific content of microsomal cytochrome b5 in both chow-and liquid diet-fed hamsters while cytochrome P450 levels were unchanged in chow-fed animals and increased in liquid diet-fed animals. Microsomes from animals receiving ethanol in their drinking water exhibited decreased rates of microsomal aryl hydrocarbon hydroxylase activity and postmitochondrial supernatant mediated mutagenicity of benzo(a)pyrene. In contrast, microsomes from hamsters receiving ethanol in liquid diets showed no changes in either of these two activities. When the observed rates of 7,8 and 9,10 diol formation per nmole P450 for chow-fed animals are plotted vs. the b5/P450 ratio a positive correlation was observed suggesting that cytochrome b5 participates directly in the microsomal metabolism of benzo(a)pyrene.

Alcoholism↗
PubMed1986

Resorufin inhibits the in vitro metabolism and mutagenesis of benzo(a)pyrene.

7-Hydroxyphenoxazin-3-one, commonly known as resorufin, strongly inhibits benzo(a)pyrene-induced mutation in the Ames bacterial reversion assay. The antimutagenic mechanism is due in part to redox cycling of resorufin with the concommitant transfer of reducing equivalents from NADPH to molecular oxygen. The diversion of electrons from cytochrome P-450 enzymes results in a large decrease in the percent of benzo(a)pyrene metabolized by rat liver microsomes as measured by HPLC. Resorufin stimulated a non-stoichiometric consumption of NADPH and was reduced in S-9 or microsomal solutions. These processes were sensitive to dicumarol and NADP inhibition to different degrees in each liver fraction. This suggests two pathways are involved in resorufin redox cycling, one involving DT-diaphorase and the other with NADPH cytochrome P-450 reductase. Oxygen was shown to be an electron acceptor for S-9 mediated resorufin redox cycling, but was not consumed by a microsomal solution in the presence of resorufin and NADPH.

Animals↗
PubMed1990

Evidence for nonintercalative complexes formed from the reversible binding of benzo[a]pyrene metabolites to closed-circular, single-stranded M13mp19 DNA.

The fluorescence excitation spectrum of complexes formed from the reversible binding of the proximate carcinogen, trans-7,8-dihydroxy-7,8-dihydro-benzo[a]pyrene (BP78D) to closed-circular, single-stranded, viral M13mp19 DNA (SS M13 DNA) exhibits a red-shift of 5 nm compared to the spectrum of BP78D measured without DNA or with native, calf thymus DNA. In SS M13 DNA which is 0.10 mM in PO4-, the fluorescence intensity of BP78D is 2.3 times smaller than the intensity measured without DNA; however, the fluorescence lifetime (42.7 nsec) of BP78D with SS M13 DNA is 1.7-1.8 times larger than the lifetimes of BP78D measured without DNA or with calf thymus DNA. These results are consistent with the conclusion that, in addition to binding sites which cause fluorescence quenching, SS M13 DNA contains sites which permit formation of BP78D inclusion complexes that have weaker interactions with nucleotide bases than those occurring in intercalated complexes. The association constant (1.45 +/- 0.01 x 10(5) M-1) for the binding of BP78D to SS M13 DNA is more than 9.0 times larger than that for binding to calf thymus DNA. It is 7.1 times larger than that for the binding of the less genotoxic metabolite, trans-4,5-dihydroxy-4,5-dihydrobenzo[a]pyrene (BP45D) to SS M13 DNA. UV Photoelectron data and results from ab initio molecular orbital calculations suggest that a difference in polarizability contributes to the greater SS M13 DNA binding of BP78D compared to that of BP45D.

Animals↗
PubMed1985

Benzo[a]pyrene metabolism and DNA adduct formation mediated by English sole liver enzymes.

Tritiated benzo[a]pyrene (BaP) and (+/-)-7,8-dihydroBaP (BaP 7,8-dihydrodiol) were incubated with English sole liver microsomes in the presence of salmon testes DNA. The modified deoxynucleosides were isolated by Sephadex LH-20 column chromatography and analyzed by reverse-phase high-pressure liquid chromatography (HPLC). A single, major adduct (60-68% of the total modified deoxynucleosides) was formed when either BaP or BaP 7,8-dihydrodiol was incubated with sole liver microsomes and DNA. Although other minor BaP-DNA adducts were formed, none represented greater than 3% of the total adducts. The major adduct had a retention time on HPLC identical to that of the N2-[10 beta (7 beta, 8 alpha, 9 alpha-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene)yl]-deoxy-guanosine (7R-anti-BPDE/trans-dG) adduct formed when anti-BPDE, the ultimate carcinogen of BaP in mammals, was incubated with DNA. Analysis of the Bay region tetrols showed that only the 7 alpha, 8 beta, 9 beta, 10 alpha-tetrahydroxy-7,8,9,10-tetrahydroBaP, a hydrolysis product of the anti-BPDE, was formed when BaP was incubated with sole liver microsomes. When BaP 7,8-dihydrodiol was used as the substrate, the 7 alpha, 8 beta, 9 beta, 10 alpha-, 7 alpha, 8 beta, 9 alpha, 10 beta-, and 7 alpha, 8 beta, 9 alpha, 10 alpha-tetrahydroxy-7,8,9,10-tetrahydroBaP's were formed, indicating the formation of both anti- and syn-BPDE. The ratio of tetrols of anti-BPDE/syn-BPDE was 2; however, the ratio of adducts of anti-BPDE/syn-BPDE was 20. Thus, the findings show that hepatic microsomes of English sole, a fish species having a high incidence of liver neoplasia in chemically contaminated estuaries, metabolized BaP and BaP 7,8-dihydrodiol stereoselectively to form predominantly the 7R-anti-BPDE/trans-dG adduct.

Animals↗
PubMed1985

Benzo[a]pyrene metabolism in mouse liver. Association of both 7,8-epoxidation and covalent binding of a metabolite of the 7,8-diol with the Ah locus.

The 7,8-epoxidation of benzo[a]pyrene, and the 9,10-epoxidation of benzo[a]-pyrene trans-7,8-dihydrodiol coupled with covalent binding of the highly reactive diol-epoxide, are two key P-450-mediated reactions believed to be important in cancer initiation, mutagenesis and teratogenesis. New assays for these two reactions were developed with mouse liver microsomes. These two activities have apparent Km values (approximately 6 microM) similar to that of aryl hydrocarbon hydroxylase activity. Twenty-six individual 3-methylcholanthrene-treated Ahb/Ahd and Ahd/Ahd progeny of the (C57BL/6N)(DBA/2N) F1 X DBA/2N backcross were studied. Both of the newly described activities appear to represent P-450 protein(s) that are responsible for aryl hydrocarbon hydroxylase activity and that are coordinately controlled by the Ahb allele.

Animals↗
PubMed1988

Radical cations in the horseradish peroxidase and prostaglandin H synthase mediated metabolism and binding of benzo[a]pyrene to deoxyribonucleic acid.

Metabolism and DNA binding studies are used to investigate mechanisms of activation for carcinogens. In this paper we describe metabolism of benzo[a]pyrene (BP) and 6-fluorobenzo[a]pyrene (6-FBP) by two peroxidases, horseradish peroxidase (HRP) and prostaglandin H synthase (PHS), which are known to catalyze one-electron oxidation. In addition, binding of BP and BP quinones to DNA was compared in the two enzyme systems. The only metabolites formed from BP or 6-FBP by either enzyme were the quinones, BP 1,6-, 3,6- and 6,12-dione. HRP metabolized BP and 6-FBP to the same extent and produced the same proportion of each dione from both compounds, approximately 40% each of BP 1,6- and 3,6-dione and 20% BP 6,12-dione. PHS formed twice as much quinones from BP as from 6-FBP and produced relatively more BP 3,6-dione from 6-FBP (46%) compared to BP (30%) and relatively less BP 6,12-dione from 6-FBP (16%) compared to BP (33%). Removal of the fluoro substituent in the metabolism of 6-FBP is consistent only with an initial one-electron oxidation of the substrate. Since BP quinones were the only products formed in HRP- and PHS-catalyzed activation of BP, their possible binding to DNA was compared to that of BP. No significant binding of BP quinones to DNA occurred with either HRP or PHS. These results, coupled with those from other chemical and biochemical experiments, demonstrate that HRP- and PHS-catalyzed one-electron oxidation of BP to its radical cation is the mechanism of formation of quinones and binding of BP to DNA.

Benzo(a)pyrene↗
PubMed1989

Intracellular lipoproteins as carriers for 2,3,7,8-tetrachlorodibenzo-p-dioxin and benzo(a)pyrene in rat and mouse liver.

The possible role of hepatic lipoproteins as intracellular carriers in the transport of 2,3,7,8-tetrachlorodibenzo-p-dioxin and benzo(a)pyrene was assessed by in vitro and in vivo studies. Following administration of [3H]2,3,7,8-tetrachlorodibenzo-p-dioxin or unlabelled 2,3,7,8-tetrachlorodibenzofuran to C57 BL/6 mice or Sprague-Dawley rats these compounds were bound to lipoproteins which subsequently underwent rapid and pronounced degradative processing, possibly catalysed by lipoprotein lipase, to heavier entities. At the highest doses of xenobiotics administered, an almost complete disappearance of lipoprotein particles was observed. The in vitro incubation of [3H]2,3,7,8-tetrachlorodibenzo-p-dioxin-lipoprotein and [3H]benzo(a)pyrene-lipoprotein complexes with separated Ah receptor and 4S protein, respectively, demonstrated that a passive transfer occurred; the latter was likely dependent on both the relative affinities of the ligands towards the different cellular binding components as well as on their quantitative binding capacity. Taken together, these findings support the idea of a carrier-role for lipoproteins in the intracellular transport of hydrophobic xenobiotics and it may be asked whether the widespread modulators of lipoprotein level such as fibrates or others affect drug transfer or action.

Animals↗
PubMed1981

Benzo[a]pyrene metabolism in organ cultures of human endometrium.

Twenty-six specimens of normal human endometrium were obtained for studies of [3H]benzo[alpha]pyrene metabolism in short-term organ culture. The tissues were capable of converting benzo[alpha]pyrene (BP) to oxygenated derivatives which co-chromatographed with dihydrodiols, quinones and monohydroxy derivatives of BP. A sulfate conjugate of a monohydroxy BP was also found among the acetone/ethyl acetate soluble products. When the acetone/ethyl acetate soluble metabolites were analyzed using high-pressure liquid chromatography (HPLC), the proportion of metabolites were found to vary greatly from specimen to specimen. Eight women smoked cigarettes but the BP metabolite profiles from organ cultures of endometrial tissue from these women did not differ from those who did not smoke. The average value for sulfate conjugates of monohydroxy BP was significantly lower in endometrial tissue from three postmenopausal women (ages 49, 57 and 58) than among premenopausal women. Specimens from premenopausal women which had been in organ culture for 2 weeks prior to the addition of [3H] BP produced metabolite profiles similar to those of specimens from postmenopausal women with a greatly reduced proportion of BP-phenol sulfate conjugates. These data suggest that the absence of hormonal stimulus (i.e., advanced age or conditions of organ culture) may affect the metabolism of BP in human endometrial tissue.

Adult↗