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PubMed1986

Tumor-initiating activity of major in vivo metabolites of indeno[1,2,3-cd]pyrene on mouse skin.

Indeno[1,2,3-cd]pyrene is a ubiquitous environmental pollutant which is active as a tumor initiator and complete carcinogen on mouse skin and is carcinogenic in rat lung. The major metabolites of indeno[1,2,3-cd]pyrene as formed in vivo in mouse skin have been identified. 8-Hydroxyindeno[1,2,3-cd]pyrene is the most abundant metabolite identified. 9-Hydroxyindeno[1,2,3-cd]pyrene and trans-1,2-dihydro-1,2-dihydroxyindeno[1,2,3-cd]pyrene are also major in vivo metabolites in mouse skin. Several minor metabolites were also identified. Among these are trans-1,2-dihydro-1,2,8-trihydroxyindeno[1,2,3-cd]pyrene, trans-1,2-dihydro-1,2,9-trihydroxyindeno[1,2,3-cd]pyrene, indeno[1,2,3-cd]pyrene-1,2-dione, and 10-hydroxyindeno[1,2,3-cd]pyrene. The tumor-initiating activity of several of the major in vivo metabolites of indeno[1,2,3-cd]pyrene has been investigated on mouse skin. Trans-1,2-dihydro-1,2-dihydroxyindeno[1,2,3-cd]pyrene and 1,2-dihydro-1,2-epoxyindeno[1,2,3-cd]pyrene both produced an 80% incidence of tumor-bearing mice at a total initiating dose of 1.0 mg. The activity of this K-region dihydrodiol and K-region oxide was, however, less than that of the parent hydrocarbon. These data suggest that 1,2-dihydro-1,2-epoxyindeno[1,2,3-cd]pyrene, which is an ultimate mutagenic metabolite of indeno[1,2,3-cd]pyrene, is not the ultimate tumorigenic metabolite on mouse skin. 8-Hydroxyindeno[1,2,3-cd]pyrene, which is mutagenic when assayed in the presence of a microsomal activation system, exhibited only weak tumor-initiating activity. These results indicate that the principal metabolic activation pathways associated with the mutagenic activity of indeno[1,2,3-cd]pyrene are not related to its tumor-initiating activity on mouse skin.

Animals↗

PubMed2006

Study of biochemical pathways and enzymes involved in pyrene degradation by Mycobacterium sp. strain KMS.

Pyrene degradation is known in bacteria. In this study, Mycobacterium sp. strain KMS was used to study the metabolites produced during, and enzymes involved in, pyrene degradation. Several key metabolites, including pyrene-4,5-dione, cis-4,5-pyrene-dihydrodiol, phenanthrene-4,5-dicarboxylic acid, and 4-phenanthroic acid, were identified during pyrene degradation. Pyrene-4,5-dione, which accumulates as an end product in some gram-negative bacterial cultures, was further utilized and degraded by Mycobacterium sp. strain KMS. Enzymes involved in pyrene degradation by Mycobacterium sp. strain KMS were studied, using 2-D gel electrophoresis. The first protein in the catabolic pathway, aromatic-ring-hydroxylating dioxygenase, which oxidizes pyrene to cis-4,5-pyrene-dihydrodiol, was induced with the addition of pyrene and pyrene-4,5-dione to the cultures. The subcomponents of dioxygenase, including the alpha and beta subunits, 4Fe-4S ferredoxin, and the Rieske (2Fe-2S) region, were all induced. Other proteins responsible for further pyrene degradation, such as dihydrodiol dehydrogenase, oxidoreductase, and epoxide hydrolase, were also found to be significantly induced by the presence of pyrene and pyrene-4,5-dione. Several nonpathway-related proteins, including sterol-binding protein and cytochrome P450, were induced. A pyrene degradation pathway for Mycobacterium sp. strain KMS was proposed and confirmed by proteomic study by identifying almost all the enzymes required during the initial steps of pyrene degradation.

Bacterial Proteins↗

PubMed2004

Degradation of benzo[a]pyrene by Mycobacterium vanbaalenii PYR-1.

Metabolism of the environmental pollutant benzo[a]pyrene in the bacterium Mycobacterium vanbaalenii PYR-1 was examined. This organism initially oxidized benzo[a]pyrene with dioxygenases and monooxygenases at C-4,5, C-9,10, and C-11,12. The metabolites were separated by reversed-phase high-performance liquid chromatography (HPLC) and characterized by UV-visible, mass, nuclear magnetic resonance, and circular dichroism spectral analyses. The major intermediates of benzo[a]pyrene metabolism that had accumulated in the culture media after 96 h of incubation were cis-4,5-dihydro-4,5-dihydroxybenzo[a]pyrene (benzo[a]pyrene cis-4,5-dihydrodiol), cis-11,12-dihydro-11,12-dihydroxybenzo[a]pyrene (benzo[a]pyrene cis-11,12-dihydrodiol), trans-11,12-dihydro-11,12-dihydroxybenzo[a]pyrene (benzo[a]pyrene trans-11,12-dihydrodiol), 10-oxabenzo[def]chrysen-9-one, and hydroxymethoxy and dimethoxy derivatives of benzo[a]pyrene. The ortho-ring fission products 4-formylchrysene-5-carboxylic acid and 4,5-chrysene-dicarboxylic acid and a monocarboxylated chrysene product were formed when replacement culture experiments were conducted with benzo[a]pyrene cis-4,5-dihydrodiol. Chiral stationary-phase HPLC analysis of the dihydrodiols indicated that benzo[a]pyrene cis-4,5-dihydrodiol had 30% 4S,5R and 70% 4R,5S absolute stereochemistry. Benzo[a]pyrene cis-11,12-dihydrodiol adopted an 11S,12R conformation with 100% optical purity. The enantiomeric composition of benzo[a]pyrene trans-11,12-dihydrodiol was an equal mixture of 11S,12S and 11R,12R molecules. The results of this study, in conjunction with those of previously reported studies, extend the pathways proposed for the bacterial metabolism of benzo[a]pyrene. Our study also provides evidence of the stereo- and regioselectivity of the oxygenases that catalyze the metabolism of benzo[a]pyrene in M. vanbaalenii PYR-1.

Benzopyrenes↗

PubMed1995

Stereo-selectivity and regio-selectivity in the metabolism of 7,8-dihydrobenzo[a]pyrene by cytochrome P450, epoxide hydrolase and hepatic microsomes from 3-methylcholanthrene-treated rats.

The active site of cytochrome P450 1A1 has been probed with the substrate 7,8-dihydrobenzo[a]pyrene using a purified, reconstituted system composed of cytochrome P450 1A1, NADPH-cytochrome c reductase and lipid in the presence or absence of epoxide hydrolase. The turnover of the substrate was found to be 38 nmol/nmol of cytochrome P450/min. The metabolic products that were identified are: a phenolic 7,8-dihydrobenzo[a]pyrene (20-29%); 9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (17-28%); benzo[a]pyrene (12-19%); 7-hydroxy-7,8-dihydrobenzo[a]pyrene (13-16%); 8-hydroxy-7,8-dihydrobenzo[a]pyrene (7-15%); 3-hydroxybenzo[a]pyrene (7-15%); 4,5-epoxy-4,5,7,8-tetrahydrobenzo[a]pyrene (0-4%); and a triol of 7,8,9,10-tetrahydrobenzo[a]pyrene (0-4%). 9,10-Epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene undergoes rapid hydrolysis to cis- and trans-9,10-dihydroxy-dihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (2:1) by benzylic attack of water at C-10. Approximately 71% of the trans diols are derived from (+)-(9S,10R)-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, indicating that cytochrome P450 1A1 has more than a 2:1 preference for selective epoxidation of an enantiotopic face of 7,8-dihydrobenzo[a]pyrene. This stereo-selectivity agrees with the postulated stereo-selectivity predicted by a previously described active site model for cytochrome P450 1A1. Epoxide hydrolase in pure form or in hepatic microsomes catalyzes the hydrolysis of 9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, which is inhibited by 1,1,1-trichloropropane 2,3-oxide. The (+)-(9S,10R)-isomer of the epoxide is slightly preferred as a substrate over its enantiomer and is cleaved by benzylic and nonbenzylic attack. Only benzylic attack was found with (-)-(9R,10S)-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene.

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

PubMed2003

Pyrene biotransformation products as biomarkers of polycyclic aromatic hydrocarbon exposure in terrestrial Isopoda: concentration-response relationship, and field study in a contaminated forest.

In this study, biotransformation products of pyrene were measured in the hepatopancreas of terrestrial isopods as biomarkers of polycyclic aromatic hydrocarbon (PAH) exposure. These products--pyrene-1-glucoside, pyrene-1-sulfate, an unknown pyrene conjugate, and 1-hydroxypyrene--were quantitated using high-performance liquid chromatography (HPLC) with fluorescence detection. In a controlled exposure experiment, a linear relationship was established between pyrene exposure and pyrene metabolite concentrations in the hepatopancreas of Porcellio scaber Latr. To this end, isopods of the species P. scaber were exposed to a range of pyrene concentrations spiked to their food. A linear response was found for all pyrene conjugates in the range 0.67 to 67 microg/g of pyrene (dry wt). Hepatopancreatic pyrene metabolite concentrations were also measured in isopods (P. scaber and Oniscus asellus L.) from PAH-contaminated field sites. The sites and the inhabiting isopods were located in a gradient of atmospheric PAH deposition caused by a nearby blast furnace plant. The highest levels of conjugated 1-hydroxypyrene in the hepatopancreas were 3.8 pmol/g fresh weight (pyrene-1-glucoside) and 2.8 pmol/g fresh weight (pyrene-1-sulfate) (expressed on whole-body basis). The levels of the pyrene metabolites correlate with reported pyrene concentrations in spite of these sites. As pyrene is one of the most predominant PAHs, analysis of its metabolites provides a good tool for environmental risk assessment of ecosystems with regard to PAH exposure, bioavailability, and biotransformation.

Animals↗

PubMed1976

Kinetic processes in Escherichia coli membranes and cells. A laser photolysis study using derivatives of pyrene.

Pyrene and several derivatives of pyrene are used to investigate photo-induced kinetic processes in whole cells and membranes extracted from Escherichia coli. A mutant of E. coli was used which, under appropriate growth conditions, produced a complete or incomplete lipopolysaccharide in the outer membrane. The pyrene derivatives used were: pyrene sulfonic acid, pyrene butyric acid and the ester of pyrene butyric acid and 10-hydroxydecanoic acid. The pyrene chromophore was excited by the ultraviolet pulse from a Q switch, frequency-doubled, ruby laser. The lifetimes of the pyrene fluorescence in the presence of the quenchers O2, thallous ion (T1+), I-and CH3NO2 were measured and tabulated as second order rate constants. For the most part the quenching rate constants were much lower than the corresponding values observed in simple nonviscous solution, e.g. ethanol. This is interpreted as being due to the location of the probe within the membrane. The membrane inhibits the movement of the quenchers to the excited state. Cell membranes containing complete lipopolysaccharide showed significantly lower quenching rates for the probes pyrene and pyrene sulfonic acid than cell membranes with incomplete lipopolysaccharide. From an amalysis of the kinetic data it is suggested that pyrene and pyrene sulfonic acid are located near and under lipopolysaccharide and close to membrane proteins. On the other hand, no effect of lipopolysaccharide composition was observed for the probes pyrene butyric acid and pyrene butyroyl decanoic acid. This may suggest that these probes are located primarily in the lipid part of the membrane. A simple model for the outer membrane of E. coli is suggested that accounts for the observed laser-induced kinetic processes.

Biological Transport↗

PubMed2003

Pyrene-induced changes of glutathione-S-transferase activities in different microalgal species.

The glutathione-S-transferase (GST, EC 2.5.1.18) activities in different freshwater microalgal species, namely, Chlorella vulgaris, Scenedesmus quadricauda, Scenedesmus platydiscus and Selenastrum capricornutum under the control condition (without pyrene addition) and at different pyrene concentrations were compared. During 7-days incubation under the control condition (without pyrene addition), all microalgal species exhibited measurable GST activities but the activities varied significantly among species and the difference could be more than 100-fold. The addition of pyrene at concentrations ranged from 0.1 to 1.0 mg l(-1) to microalgal cultures led to changes in GST activities but the patterns of changes varied from species to species. Among the four species, remarkably decreases in GST activities were found in S. quadricauda, a species most sensitive to pyrene toxicity, at high pyrene concentrations. On the contrary, GST activities in S. platydiscus and Se. capricornutum increased significantly as pyrene concentrations increased. These two species were found to be more resistant to pyrene and had higher efficiencies in metabolising pyrene than other species. C. vulgaris did not show any significant change in their GST activities with the addition of pyrene, and pyrene was not metabolised by this species. These results suggest that pyrene-induced changes of GST activities in microalgae might be related to their resistance and their ability to metabolise pyrene. In general, the pyrene-induced changes of GST activities were higher at 4-days than at 1- and 7-days incubation in all microalgae.

Animals↗

PubMed2007

Differential utilization of pyrene as the sole source of carbon by Bacillus subtilis and Pseudomonas aeruginosa strains: role of biosurfactants in enhancing bioavailability.

AIMS: Our goal is to compare the efficiency of utilization of pyrene as the sole source of carbon for growth and energy by two nonactinomycetous groups of bacteria viz., Bacillus subtilis DM-04 and Pseudomonas aeruginosa mucoid (M) and nonmucoid (NM) strains, isolated from a petroleum-contaminated soil sample of north-east India. METHODS AND RESULTS: Bacillus subtilis DM-04 and P. aeruginosa M and NM bacterial strains were capable of secreting biosurfactant in the culture medium while growing on pyrene and their pyrene utilizing efficiency was demonstrated by correlating the bacterial growth in the presence of pyrene as the sole source of carbon along with a concomitant decrease in pyrene content from the culture medium with respect to time. The biosurfactant secreted by the respective bacterial strains enhanced the apparent solubility of pyrene by factors of 5-7 and influenced the bacterial cell surface hydrophobicity resulting in higher uptake and utilization of pyrene by bacteria. The growth of B. subtilis DM-04 and P. aeruginosa M and NM strains at the expense of pyrene after 96 h showed an assimilation of about 48.0 +/- 1.1% (mean +/- SD) and 32.0 +/- 0.6% (mean +/- SD) of pyrene carbon, respectively, showing differences in metabolism of pyrene by these bacterial strains. CONCLUSIONS: Bacillus subtilis DM-04 strain exhibited higher utilization and cellular assimilation of pyrene compared with P. aeruginosa M and NM strains. Further, the biosurfactants produced by the bacteria under study are capable of enhancing the solubility of pyrene in aqueous media and can influence the cell surface hydrophobicity of the biosurfactant-producing strains that results in a higher uptake of pyrene. SIGNIFICANCE AND IMPACT OF THE STUDY: It may be suggested that the bacteria used in this study are suitable candidates for practical field application for effective in situ bioremediation of pyrene-contaminated sites.

Bacillus subtilis↗

PubMed2000

Chemical characterization and bioactivity of polycyclic aromatic hydrocarbons from non-oxidative thermal treatment of pyrene-contaminated soil at 250-1,000 degrees C.

In this paper we report yields, identities, and mutagenicities of products from heating a polycyclic aromatic hydrocarbon (PAH)-contaminated, Superfund-related synthetic soil matrix without exogenous oxygen. We heated batch samples of soil pretreated with 5.08 wt% (by weight) pyrene in a tubular furnace under a constant flow of helium gas at 250, 500, 750, and 1,000 +/- 20 degrees C. Dichloromethane (DCM) extracts of cooled residues of heated soil and of volatiles condensed on a cold finger after 1 sec residence time at furnace temperature were assayed gravimetrically and analyzed for PAH by HPLC, HPLC coupled to mass spectrometry, and gas chromatography coupled to mass spectrometry. All four temperatures volatilized pyrene and generated other PAHs, including alkylated pyrenes. We detected bioactive PAHs in the product volatiles: cyclopenta[cd]pyrene (CPP) at 750 and 1,000 degrees C and benzo[a]pyrene (BaP) at 1,000 degrees C. We found a clean soil residue, i.e., no pyrene or other DCM extracts, only at 750 degrees C. Control experiments with uncontaminated soil, pyrene, and Ottawa sand plus 4.89 wt% pyrene revealed no CPP or BaP production from soil itself, but these experiments imply that pyrene interactions with soil, e.g., soil-bound silica, stimulate CPP and BaP production. We detected mutagenicity to human diploid lymphoblasts (in vitro) in volatiles from 1,000 degrees C heating of soil plus pyrene and sand plus pyrene, and in the residue from 500 degrees C heating of soil plus pyrene. Three plausible pathways for pyrene conversion to other PAHs are a) a reaction with light gas species, e.g., soil- or pyrene-derived acetylene; b) loss of C(2)-units followed by reaction with a PAH; and c) dimerization with further molecular weight growth via cyclodehydrogenation. This study shows that thermal treatment of PAH-polluted soil may generate toxic by-products that require further cleanup by oxidation or other measures.

Benzopyrenes↗

PubMed1984

Synthesis, spectral analysis, and mutagenicity of 1-, 3-, and 6-nitrobenzo[a]pyrene.

The mutagenic environmental pollutants 1-, 3-, and 6-nitrobenzo[a]pyrene were synthesized. Nitration of 7,8,9,10-tetrahydrobenzo[a]pyrene with sodium nitrate in trifluoroacetic acid and acetic anhydride at ambient temperature gave a mixture of 1-, 3-, and 6-nitro-7,8,9,10-tetrahydrobenzo[a]pyrene, which was separated by chromatography. Dehydrogenation of the isolated nitrotetrahydrobenzo[a]pyrenes with 2,3-dichloro-4,5-dicyano-1,6-benzoquinone produced 1-, 3-, and 6-nitrobenzo[a]pyrene in high yield. Comparison of the spectral data of these compounds with those obtained from direct nitration of benzo[a]pyrene confirmed that 1- and 3-nitrobenzo[a]pyrenes are indeed the minor products of the latter reaction. This confirmation also verifies that 1- and 3-nitrobenzo[a]pyrene were the minor nitrated products of benzo[a]pyrene formed in model air atmospheres. The 1-, 3-, and 6-nitrobenzo[a]pyrene were mutagenic in Salmonella typhimurium tester strains TA98 and TA100 in the presence of a mammalian microsomal (S9) activating system. Both 1- and 3-nitrobenzo[a]pyrene, but not 6-nitrobenzo[a]pyrene, were also direct-acting mutagens in these strains. However, only 6-nitrobenzo[a]pyrene exhibited weak mutagenic activity when tested in Chinese hamster ovary cells, while only 3-nitrobenzo[a]pyrene produced a concentration-dependent decrease in cellular survival.

Benzopyrenes↗

PubMed2005

Limited microbial degradation of pyrene metabolites from the estuarine polychaete Nereis diversicolor.

We compared microbial mineralization of [4,5,9,10-14C]pyrene and its eukaryotic [4,5,9,10-14C]pyrene metabolites in estuarine sediments. Metabolites were obtained by exposing the estuarine deposit-feeding polychaete Nereis diversicolor to sediment-associated 14C-pyrene, followed by homogenization of the worms and extraction of the pyrene-metabolites. In sediment from a pristine Danish Fjord only 2.6% of the added metabolite-label and 1.7% of the pyrene-label were mineralized to 14CO2 during 175 days incubation. Pre-exposure of the pristine sediment to unlabelled pyrene for 60 days increased the mineralization potential for 14C-pyrene substantially, as 81.2% was mineralized to 14CO2 during 95 days incubation, whereas 14C-pyrene metabolite label was unaffected by pre-exposure to pyrene. In comparison, naturally aged bunker-oil contaminated sediment did not show elevated potentials for mineralization of neither 14C-pyrene nor 14C-metabolites. Six bacterial strains of known pyrene degraders were tested for growth on crystalline 1-hydroxypyrene. 1-Hydroxypyrene is the only intermediate eucaryotic metabolite of pyrene. The results indicate that 1-hydroxypyrene was not utilized as a sole source of carbon and energy by any of them. In addition, respiration was depressed in all six strains when exposed to crystalline 1-Hydroxypyrene, demonstrating an acute toxic effect of 1-hydroxypyrene. The results presented here suggest that microbial degradation of pyrene is not enhanced by release of aqueous and polar metabolites by marine invertebrates.

Animals↗

PubMed2006

Fluorescence-based evidence for adsorptive binding of pyrene to effluent dissolved organic matter.

Using fluorescence intensity measurements, pyrene interactions with different types of effluent dissolved organic matter (EDOM) originated from treated municipal wastewater are examined. Multiple observations show that fluorescence intensity of pyrene-EDOM solutions is non-linearly related to pyrene concentration, with distinct concave-up dependence. Testing the effect of pyrene concentration on fluorescence intensity of pyrene-EDOM solutions provides a tool to examine whether binding of an organic compound to EDOM follows linear or non-linear isotherm. Possible coupling between static and dynamic quenching effects was addressed while analyzing fluorescence data. Limited number of EDOM binding sites results in a non-linear binding isotherm such that the concept of pyrene "partitioning" between aqueous phase and "bulky" EDOM organic phase is hardly relevant. Maximal EDOM capacity for pyrene binding is estimated approximately as 0.1% ww(-1). Examination of the differences between the total fluorescence intensity of pyrene-EDOM solution and the fluorescence intensities of separated constituents (pyrene and EDOM) was used to illustrate the accumulation of pyrene-EDOM complexes and saturation of some EDOM binding sites. Strong interactions between pyrene and EDOM binding sites may result in pyrene distribution coefficients differing at least by a factor 3.5-7 at varying pyrene concentrations.

Adsorption↗

PubMed2005

Pyrene is highly emissive when attached to the RNA duplex but not to the DNA duplex: the structural basis of this difference.

Through binding and fluorescence studies of oligonucleotides covalently attached to a pyrene group via one carbon linker at the sugar residue, we previously found that pyrene-modified RNA oligonucleotides do not emit well in the single-stranded form, yet the attached pyrene emits with a significantly high quantum yield upon binding to a complementary RNA strand. In sharp contrast, similarly modified pyrene-DNA probes exhibit very weak fluorescence both in the double-stranded and single-stranded forms. The pyrene-modified RNA oligonucleotides therefore provide a useful tool for monitoring RNA hybridization. The purpose of this paper is to present the structural basis for the different fluorescence properties of pyrene-modified RNA/RNA and pyrene-modified DNA/DNA duplexes. The results of absorption, fluorescence anisotropy and circular dichroism studies all consistently indicated that the pyrene attached to the RNA duplex is located outside of the duplex, whereas the pyrene incorporated into the DNA duplex intercalates into the double helix. (1)H NMR measurements unambiguously confirmed that the pyrene attached to the DNA duplex indeed intercalates between the base pairs of the duplex. Molecular dynamics simulations support these differences in the local structural elements around the pyrene between the pyrene-RNA/RNA and the pyrene-DNA/DNA duplexes.

Circular Dichroism↗

PubMed1983

Vitamin K as a regulator of benzo(a)pyrene metabolism, mutagenesis, and carcinogenesis. Studies with rat microsomes and tumorigenesis in mice.

Vitamin K3 inhibits the conversion of benzo(a)pyrene to its more polar metabolites in an in vitro rat liver microsomal system. Vitamin K3 also inhibits benzo(a)pyrene metabolism in rat liver fragments and reduces its mutagenicity in the Ames test. Higher concentrations of vitamin K3 are required to comparably reduce benzo(a)pyrene metabolism when the microsomal system has been induced with 3-methylcholanthrene. High pressure liquid chromatography analysis of the products of benzo(a)pyrene metabolism shows a uniform reduction of all the metabolic products. When tumors were induced in ICR/Ha female mice by the intraperitoneal injection of benzo(a)pyrene, those mice given vitamin K3 before or both before and after benzo(a)pyrene had a slower rate of tumor appearance and tumor death rate as compared with those receiving benzo(a)pyrene alone. However, vitamin K1 increased the rate of tumor death while vitamin K deprivation and warfarin decreased the rate of tumor appearance and death in benzo(a)pyrene-injected mice. These studies indicate that vitamin K3 is an inhibitor of aryl hydrocarbon hydroxylase and reduces the carcinogenic and mutagenic metabolites in vitro, and inhibits benzo(a)pyrene tumorigenesis in vivo. That vitamin K1 enhances the benzo(a)pyrene effect while warfarin and vitamin K deficiency inhibit benzo(a)pyrene tumorigenesis indicates that vitamin K1, vitamin K deprivation, or possibly blockade of its metabolic cycle also modulates benzo(a)pyrene metabolism in vivo but by a mechanism or at a site different from the vitamin K3 effect. The vitamin K series should be considered as capable of serving a regulatory function in the metabolism of benzo(a)pyrene and possibly other compounds metabolized through the mixed function oxidase system.

Aflatoxin B1↗

PubMed1980

Mutagenicity and tumor-initiating activity of cyclopenta(c,d)pyrene and structurally related compounds.

The biological activities of benzo(a)pyrene, cyclopenta(c,d)pyrene, and 12 other structurally related compounds were assessed by mutagenicity studies with bacterial and mammalian cells and/or skin tumorigenicity studies with mice. The ability of the parent hydrocarbons to be metabolically activated to mutagenic products was examined in strains TA98 and TA100 of Salmonella typhimurium, using 3 experimental protocols. In each case, cyclopenta(c,d)pyrene was metabolically activated to products mutagenic to the bacteria to a greater extent than was benzo(a)pyrene. However, 7,8-dihydrobenzo(a)pyrene and 0,10-dihydrobenzo(e)pyrene were the best substrates for metabolic activation to bacterial mutagens. Highly purified epoxide hydrase added to a purified and reconstituted monooxygenase system readily abolished the mutagenic activity observed in strain TA100 of S. typhimurium when cyclopenta(c,d)pyrene was the substrate, but not when benzo(a)pyrene was the substrate. Inherent mutagenicity of several epoxides of the hydrocarbons generally paralleled the ability of their potential metabolic precursors to be activated to mutagens. 1-Pyrenyloxirane and 10,11-dihydrocycloheptapyrene 8,9-oxide were highly mutagenic in strains TA98 and TA100 of S. typhimurium, and in the former strain these activities were comparable to that observed with 9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, 4-Pyrenyloxirane was significantly less mutagenic than was 1-pyrenyloxirane in both strains of bacteria and in mammalian cells. Benzo(a)pyrene was over 20 times more tumorigenic than was cyclopenta-(c,d)pyrene, and it was the most potent of the 11 compounds tested for tumor-initiating activity in 2-stage initiation-promotion experiments on the skin of mice. Cyclopenta(c,d)pyrene had tumor-initiating activity comparable to that of benzo-(a)anthracene, but it was significantly less active than chrysene. Thus, contrary to inferences made from its high mutagenic activity, cyclopenta(c,d)pyrene is a weak tumor initiator on mouse skin.

Animals↗

PubMed1976

Mutagenicity and cytotoxicity of benzo(a)pyrene arene oxides, phenols, quinones, and dihydrodiols in bacterial and mammalian cells.

Twenty-nine benzo(a)pyrene derivatives were tested for mutagenic acitivity without metabolic activation in Salmonella typhimurium strains TA98, TA100, and TA1538 and in Chinese hamster V79 cells. The compounds studied included 4 arene oxides, all 12 isomeric phenols, 5 quinones, and 8 dihydrodiols. Benzo(a)pyrene 4,5-oxide was the most mutagenic of the compounds tested in both the bacterial and mammalian systems. The other arene oxides [benzo(a)pyrene 7,8-, 9,10-, and 11,12-oxides] were only weakly mutagenic in the S. typhimurium strains. However, in Chinese hamster V79 cells benzo(a)pyrene 11,12-oxide. Among the phenols, 6-hydroxybenzo(a)pyrene and 12-hydroxybenzo(a)pyrene were moderately mutagenic in strain TA98 of S. typhimurium, and 6-hydroxybenzo(a)pyrene was moderately mutagenic in V79 cells. The other 10 phenols, 5 quinones [benzo(a)pyrene 1,6-, 3,6-, 4,5-, 6, 12-, and 11,12-quinones] and 8 dihydrodiols [benzo(a)pyrene cis-4,5,trans-4,5-, cis-7,8-, trans-7,8-, cis-9,10-, trans-9,10-, cis-11,12-, and trans-11, 12-dihydrodiols] were eitherinactive or only weekly mutagenic. 1-Hydroxybenzo(a)pyrene and 3-hydroxybenzo(a)pyrene were weakly mutagenic in strain TA98 of S. typhimurium, and benzo(a)pyrene 7,8-dihydrodiol was weakly mutagenic in V79 cells. Benzo(a)pyrene 11,12-quinone was extremely cytotoxic to the V79 cells but had no observable toxicity in the bacterial strains.

Animals↗

PubMed2002

The adaptation of two similar soils to pyrene catabolism.

The development of pyrene catabolic activity was assessed in two similar soils (pasture and woodland) amended with 100 mg pyrene kg(-1) In the pasture and woodland soils, significant mineralisation of 14C-pyrene was observed after 8 and 76 weeks soil-pyrene contact times, respectively. In both soils, there were significant decreases (P<0.05) in the lag times and significant increases (P <0.05) in the maximum rates and extents of 14C-pyrene mineralised with increasing soil-pyrene contact time. A microbial inoculum was added to the woodland soil to assess if the previously added, but undegraded 14C-pyrene was bioavailable at 16 and 24 weeks. This resulted in the immediate mineralisation of the previously added 14C-pyrene, indicating that it was bioavailable but that the microbial community in the woodland soil had not developed the ability to mineralise pyrene. The relative contributions of the indigenous microflora to 14C-pyrene mineralisation were assessed by the addition of celective inhibitors, with bacteria seeming to be responsible for the mineralisation of pyrene in both soils. It is suggested that the rate of pyrene-transfer from the soil to the microorganisms was lower in the woodland soil due to its higher organic matter content.

Adaptation, Physiological↗

PubMed2004

Solid-state NMR characterization of pyrene-cuticular matter interactions.

One- and two-dimensional nuclear magnetic resonance (NMR) experiments were performed on Agave americana cutan and tomato cutin to examine the interactions between a hydrophobic pollutant, pyrene, and cuticular material. Variable-temperature NMR experiments show that cutan, an acid- and base-resistant cuticular biopolymer, undergoes the characteristic melting behavior of "polyethylene-like" crystallites, while the tomato cutin does not. The melting point of A. americana cutan was found to be approximately 360 K, which is consistent with the thickness of the polyethylene crystallites of 30-40 methylene units. Sorption models predict that the sorption behavior of hydrophobic pollutants should depend on the phase of the cuticular material. 13C NMR experiments on labeled pyrene were performed. The 13C T1 of pyrene decreases significantly from that of crystalline pyrene upon sorption to both tomato fruit cutin and A. americana cutan, indicating that the pyrene is mobile upon sorption. Magic angle spinning experiments at low spinning frequencies (2-4 kHz) provided the chemical shift anisotropy (CSA) parameters delta, the anisotropy, and eta, the asymmetry parameter, for crystalline and sorbed pyrene. For crystalline pyrene, two types of crystallographically distinctive pyrenes were observed. The first had delta = -97.4+/-0.5 ppm and eta = 0.934+/-0.006, while the second had delta = -98.1+/-0.5 ppm and eta = 0.823+/-0.008. After sorption to cutan, these CSA parameters were found to be delta = -78.9+/-5.3 ppm and eta < 0.70 independent of the length of time since completion of the sorption procedure. In tomato cutin, the CSA parameters were found to be dependent upon the time since completion of the sorption procedure. One and one-half months after sorption, delta was found to have a value of -30.4 ppm < delta < 0.0 ppm and eta was undeterminable, while after 22 months these values become delta = -80.0 +/-3.3 ppm and eta< 0.42. These changes in the CSA parameters demonstrate that upon sorption of pyrene to cutan, the pyrene undergoes anisotropic motion, while in cutin pyrene initially can tumble isotropically, but after 22 months this motion also becomes anisotropic. 2D heteronuclear correlation experiments indicate that pyrene is in close proximity to aliphatic cuticular materials after sorption. This work is directly relevant toward understanding the physical and chemical mechanisms of pollutant sorption to soil organic matter and, thus, help develop improved sorption models and pollution remediation techniques.

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