Planar Aromatic Compounds Research Articles

Xenobiotic-inducible expression of murine glutathione S-transferase Ya subunit gene is controlled by an electrophile-responsive element.

Glutathione S-transferase (GST) Ya subunit gene expression is induced in mammalian tissues by two types of chemical agents: (i) planar aromatic compounds (e.g., 3-methylcholanthrene, beta-naphthoflavone, and 2,3,7,8-tetrachlorodibenzo-p- dioxin) and (ii) electrophiles (e.g., trans-4-phenyl-3-buten-2-one and dimethyl fumarate) or compounds easily oxidized to electrophiles (e.g., tert-butylhydroquinone). To study the mechanism of this induction, we have introduced deletions in the 5' flanking region of a mouse GST Ya subunit gene, fused it to the coding sequence for chloramphenicol acetyltransferase (CAT) activity, and transfected the Ya-CAT genes for expression into hepatoma cells. We show that a single cis-regulatory element, between nucleotides -754 and -713 from the start of transcription, is responsible for the induction by both planar aromatic and electrophilic compounds. Using murine hepatoma cell mutants defective in either the Ah-encoded aryl hydrocarbon receptor (BPrc1 mutant) or in cytochrome P1-450 gene (c1 mutant), we show that induction by planar aromatic but not by electrophilic inducers requires a functional Ah receptor and cytochrome P1-450 activity. From this it is concluded that Ya gene activation by planar aromatic compounds involves metabolism of these inducers by the phase I xenobiotic-metabolizing cytochrome P1-450 system into electrophilic compounds, which is consistent with a recently proposed model [Prochaska, H. J. & Talalay, P. (1988) Cancer Res. 48, 4776-4782]. Therefore, the regulatory sequence of the Ya gene should be considered an electrophile-responsive element (EpRE) activated exclusively by inducers containing an electrophilic center. An EpRE-containing 41-bp oligonucleotide ligated at the -187 site of the Ya gene promoter confers upon it an increase in basal activity and xenobiotic inducibility. The basal activity augments with the number of EpRE copies. DNase I protection patterns show the protection of the EpRE domain by a nuclear factor(s) that becomes more abundant upon exposure of Hepa 1c1c7 cells to tert-butylhydroquinone.

Transcriptional regulation of the rat glutathione S-transferase Ya subunit gene. Characterization of a xenobiotic-responsive element controlling inducible expression by phenolic antioxidants.

We have identified previously a xenobiotic-responsive element, which we termed the beta-naphthoflavone-responsive element, between nucleotide -722 and -682 in the 5'-flanking region of the rat glutathione S-transferase Ya subunit gene (Rushmore, T.H., King, R.G., Paulson, K.E., and Pickett, C.B. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 3826-3830). The beta-naphthoflavone-responsive element is responsible for part of the transcriptional activation of the Ya subunit gene by planar aromatic compounds but has a sequence distinct from the xenobiotic-responsive element found in multiple copies in the cytochrome P-450 IA1 gene and as a single copy in the Ya subunit gene. In the present study, we demonstrate that the beta-naphthoflavone-responsive element is required for the transcriptional activation of the Ya subunit gene by phenolic antioxidants such as t-butylhydroquinone through a mechanism that does not require functional Ah receptors. Furthermore, we present evidence that planar aromatic compounds must be metabolized before they transcriptionally activate the Ya subunit gene through the beta-naphthoflavone-responsive element. The transcriptional activation of the Ya subunit gene by planar aromatic compounds requires a functional Ah receptor. These data provide evidence that transcriptional activation of the glutathione S-transferase Ya subunit gene can be mediated by a novel xenobiotic-responsive element which is directly responsive to phenolic antioxidants such as t-butylhydroquinone. Hence we have named this new xenobiotic-responsive element the antioxidant-responsive element or ARE.

Regulation of glutathione S-transferase Ya subunit gene expression: identification of a unique xenobiotic-responsive element controlling inducible expression by planar aromatic compounds.

We have identified a region in the 5' flanking sequence of the glutathione S-transferase (RX:glutathione R-transferase, EC 2.5.1.18) Ya subunit gene that contains a unique xenobiotic-responsive element (XRE). The regulatory region spans nucleotides -722 to -682 of the 5' flanking sequence and is responsible for part of the basal level as well as inducible expression of the Ya subunit gene by planar aromatic compounds such as beta-naphthoflavone (beta-NF) and 3-methyl-cholanthrene. The DNA sequence of this region (beta-NF-responsive element) is distinct from the DNA sequence of the XRE found in the cytochrome P-450 IA1 gene. In addition to the region containing the beta-NF-responsive element, two other regulatory regions of the Ya subunit gene have been identified. One region spans nucleotides -867 to -857 and has a DNA sequence with identity to the hepatocyte nuclear factor 1 recognition motif found in several liver-specific genes. The second region spans nucleotides -908 to -899 and contains a DNA sequence with identity to the XRE found in the cytochrome P-450 IA1 gene. The XRE sequence also contributes to part of the responsiveness of the Ya subunit gene to planar aromatic compounds. Our data suggest that regulation of gene expression by planar aromatic compounds can be mediated by a DNA sequence that is distinct from the XRE sequence.

Rat liver NAD(P)H: Quinone reductase: Regulation of quinone reductase gene expression by planar aromatic compounds and determination of the exon structure of the quinone reductase structural gene

Abstract We have determined the effect of beta-naphthoflavone and the azo dye, sudan III, on the level of quinone reductase mRNA in a responsive rat hepatoma cell line. Our data indicate that both of these planar aromatic compounds produce a 4-5-fold elevation in quinone reductase mRNA. The induction of quinone reductase mRNA can be blocked by cycloheximide, suggesting a requirement for ongoing protein synthesis in the induction process. We have determined the exon structure of the quinone reductase structural gene. The gene is separated into six exons by five introns. A TATA box is located 29 base pairs upstream from the transcription initiation site. A CCAAT sequence is found at position -129, and an inverted GC box is located at position -78. Quinone reductase promoter-chlor-amphenicol acetyltransferase fusion genes containing different lengths of the 5'-flanking region were transfected into rat and human hepatoma cells. Treatment of the transfected cells with beta-naphthoflavone or sudan III resulted in a 4-5-fold elevation in chloramphenicol acetyltransferase activity. These data suggest the presence of a cis-acting regulatory element(s) in the 5'-flanking region of the quinone reductase structural gene which regulates inducible expression.

Crystal chemistry of some (alkoxyphenyl)propiolic acids. The role of oxygen and hydrogen atoms in determining stack structures of planar aromatic compounds

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCrystal chemistry of some (alkoxyphenyl)propiolic acids. The role of oxygen and hydrogen atoms in determining stack structures of planar aromatic compoundsGautam R. Desiraju and K. V. Radha KishanCite this: J. Am. Chem. Soc. 1989, 111, 13, 4838–4843Publication Date (Print):June 1, 1989Publication History Published online1 May 2002Published inissue 1 June 1989https://doi.org/10.1021/ja00195a040RIGHTS & PERMISSIONSArticle Views325Altmetric-Citations23LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (753 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Determination of tetrachlorobiphenylenes (TeCBPs) in flyash extracts containing planar aromatic compounds

A method has been developed for the separation of TeCBPs in extracts containing planar aromatic compounds. Our results indicate that extreme care should be taken in their separation and determination, since interfering compounds are likely to give overestimations regarding their levels. This method has been used successfully in analysing TeCBPs, TeCANs, TeCDDs and TeCDFs in flyash from municipal incinerators in Japan. The major planar aromatic compounds in flyash seem to be TeCDDs followed by TeCDFs > TeCANs > TeCBPs. We did not find 2367-TCBP in flyash from municipal incinerators.

Liquid chromatographic determination of planar aromatic sulphur compounds in crude oil

Oxydation des dibenzothiophenes en sulfones et analyse par chromatographie liquide haute performance

Toxic significance of planar aromatic compounds in Baltic ecosystem — New studies on extremely toxic coplanar PCBs

Baltic salmon and white-tailed eagle samples have been analyzed for organochlorine compounds including polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, polychlorinated naphtalenes and toxic coplanar PCBs. In salmon, PCB and DDT residue contents were 0.2-0.3 ug/g in fresh muscle. Chlordanes, toxaphene, hexachlorobenzene, α-hexachlorocyclohexane and γ-hexachlorcyclohexane were found at 1 – 10 ng/g levels. Significant dioxin type of toxins found were only 2,3,7,8-tetrachlorodibenzofuran (45–81 pg/g) and 3,3′,4,4′-tetrachlorobiphenyl (638–1120 pg/g). Polychloronaphtalene contents in all salmon and eagle samples were of the same order of magnitude ranging from 4 to 85 ng/g. The highest chlorohydrocarbon contents in eagle samples were for PCB 462 ug/g, sum of the DDT residues 42 ug/g, chlordanes 5.7 ug/g and HCB 1.6 ug/g. In contrary, toxaphene, α-hexachlorocyclohexane and γ-hexachlorocyclohexane were not detected in eagles. Levels of polychlorodibenzo-p-dioxins, polychlorodibenzofurans and coplanar PCBs were highest ever reported in wildlife in adult eagle samples, in liver of a juvenile eagle and in eagle egg from South Finland ranging from 1 to 13 ng/g for PCDD/Fs and from 18 to 229 ng/g for coplanar PCBs. Calculation of the TCDD-equivalents of the contents gave that dioxin toxicity load comes in great excess from the coplanar PCBs, especially from 3,3′,4,4′,5-pentachlorobiphenyl.

Glutathione S-transferase Ya subunit gene: identification of regulatory elements required for basal level and inducible expression.

The function of the 5'-flanking region of a rat glutathione S-transferase Ya subunit structural gene has been examined in homologous and heterologous cells. By using the 5'-flanking region of the Ya subunit gene fused to the structural gene encoding chloramphenicol acetyltransferase, we have identified two cis-acting regulatory elements in the upstream region of the Ya gene. One element is required for maximum basal level expression in homologous cells, whereas maximum basal level expression in homologous cells, whereas the second element is required for inducible expression of the Ya gene by planar aromatic compounds such as beta-naphthoflavone. The cis-acting element required for inducible expression of the Ya gene by beta-naphthoflavone is functional only in cells with normal dioxin receptors.

Study of the lumiescence properties of a new series of quinolizinium salts and their interaction with DNA

The spectrofluorimetric characteristic of a new group of benzo- and methyl- quinolizinium salts at room temperature and 77 LK are reported. At room temperature, linear calibration is wide; 10 -9 M 9-cyanobenzo [a] phenathro [9,10-g] quinolizinium chloride can be detected in methanolic solution and 10 -7 M in aqueous solution. The polynuclear compounds show the most intense luminescence bands, and a significant hypsochromic shift of the fluorenscence emission maximum was observed at 77 K compared with room temperature. For the 2,3-diphenyl derivatives, the presence of a methoxy substituent produces a marked Stoke's shift, because it causes a decrease in the planarity of the molecule. The benzo compounds are similar in structure to the alkaloid coralyne, which has significant antileuikemic activity. The fused planar aromatic compounds are shown to bind with DNA.

Etude MNDO des composes conjugues enneagonaux

AbstractWe present MNDO calculations of a series of nine‐membered conjugated compounds. The geometries have been fully optimized. Cyclononatetraenyl and benzocyclononatetraenyl anions, nonapyrrol, and nonathiophene appear to be planar aromatic compounds. Following MNDO, nonafulvene has a planar prefered conformation, but a polyenic structure, while nonafuran and cyclononatetraene are gauche molecules. The Universal Huckel Method (UHM), a simple all valence electron empirical technique which describes σ systems using localized MO, gives, qualitatively, the same results as the MNDO method. The quantum calculation carried out with MNDO and UHM have been used to describe the physicochemical properties of ninememberedring conjugated compounds under consideration. To our knowledge, we present here the first theoretical study dealing with nine‐membered conjugated molecules.

Effect of alkyl chain length of the stationary phase on retention and selectivity in reversed-phase liquid chromatography : Participation of solvent molecules in the stationary phase

The retention behaviour of various hydrocarbons, including n-alkanes, polynuclear aromatic hydrocarbons (PAHs) and alicyclic compounds, were examined on alkylsilylated stationary phases with trimthylsilyl (C 1), octyldimethylsilyl (C 8) and octadecyldimethylsilyl (C 18) functionality. In general, a longer alkyl chain in the stationary phase provided a longer retention time. Although the retention of rigid planar aromatic hydrocarbons relative to non-polar aromatic compounds and alkanes was much larger on the C 18 phase than on the C 8 and C 1 phases in a methanolic mobile phase, the effect of chain length was much smaller in a mobile phase containing acetonitrile. A change in the organic solvent in the mobile phase from methanol to acetonitrile resulted in grossly different selectivities between aromatic hydrocarbons and the saturated hydrocarbons regardless of the rigidity or planarity in structure of the C 18 phase, in contrast with minor changes on the C 1 and C 8 phases. The increase of organic solvent content in the mobile phase resulted in much larger retention of rigid planar aromatic compounds relative to other aromatic compounds on the C 18 phase, whereas on the C 1 and C 8 phases this effect was smaller. The retention characteristics of the C 8 phase for the hydrocarbons were found to be relatively close to those of the C 1 phase. The results suggest that the effect of chain length is influenced by both the molecular structure of the solutes and the type of organic solvents used in the mobile phase.

Phosphorescence polarisation of aromatic compounds oriented in stretched polyethylene films

Phosphorescence polarisation measurements are reported for a number of planar aromatic compounds in stretched polyethylene. The phosphorescence is to about 80% polarised perpendicular to the molecular plane. In the in-plane intensity second order Herzberg-Teller coupling terms may be at least competitive with three-center ππ spin-orbit integrals, in agreement with suggestions of Friedrich, Metz and Dörr.

The formation of graphitizing carbons from the liquid phase

The formation of graphitizing low-temperature carbons by solidification from a liquid phase proceeds via the separation of a mesophase having properties similar to those of liquid crystals. Initially, the mesophase, consisting of planar aromatic compounds of high molecular weight, separates in the isotropic liquid as spherical droplets having a considerable degree of molecular order, with the aromatic sheets stacked in parallel array. The sheets are arranged perpendicularly along one diameter of a sphere, but are curved so that they are normal to the surface. On prolonged heating the spheres coalesce and extended regions of uniform orientation may be formed; eventually a solid semi-coke is obtained. It is the generally lamellar arrangement of the molecular structure in these regions which favours the formation of graphite carbon at high temperatures. When isolated spheres are heated to graphitizing temperatures contraction occurs in the direction perpendicular to the preferred orientation. The bodies become elliptical in section and each is converted to a mass of small graphite crystals.