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Sample records for benzoapyrene diol epoxide-oligonucleotide

  1. Benzo(a)pyrene diol epoxides as intermediates in nucleic acid binding in vivo and in vitro

    DEFF Research Database (Denmark)

    Weinstein, I.B.; Jeffrey, A.M.; Jennette, K.W.; Blobstein, S.H.; Harvey, R.G.; Harris, C.; Autrup, Herman; Kasai, H.; Nakanishi, K.

    1976-01-01

    Evidence has been obtained that a specific isomer of a diol epoxide derivative of benzo(a)pyrene, (+/-)-7 beta,8alpha-dihydroxy-9alpha, 10alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, is an intermediate in the binding of benzo(a)pyrene to RNA in cultured bovine bronchial mucosa. An adduct is...

  2. Gene-specific repair of benzo[a]pyrene diol epoxide DNA damage in human cells

    International Nuclear Information System (INIS)

    Gene-specific preferential repair of UV damage has been well documented in a variety of organisms. Less is known about many other types of critical DNA lesions, the data available being not numerous and contradictory. To date, the majority of observations with UV were obtained by using T4 endonuclease V system. Recent report questions the applicability of UvrABC nuclease incision method for detecting gene-specific repair. This has stimulated our search for simple and sensitive approach based on a different principle. We have employed the idea of detection by the Southern hybridization of restriction cleavage inhibition at rare sites and developed a method for the analysis of benzo[a]pyrene diol epoxide (anti-BPDE) DNA damage in human H-ras proto-oncogene. Damage-dependent induction of individual facultative bands resulting from cleavage inhibition was observed in in vitro modified (4-50 adducts/103kb) p220-ras plasmid DNA digested with EcoRI/NotI, Xhol/Xbal/PstI, and SstI/XbaI/Pst/I. In vivo lesion formation and removal was monitored at several PstI sites distributed along the 6.4 kb single copy ras sequence. Rapid gene-specific repair was seen in primary culture of normal human fibroblasts and in SV40 transformed GM00637 cells. Surprisingly, SV40 transformed XP12BE (complementation group A) GM4429 fibroblasts also repaired anti-BPDE DNA damage at comparable levels. All investigated sites within ras sequence were repaired faster than the genome overall. The results show the utility of the above approach for fine mapping of anti-BPDE DNA lesions. Data suggests that the xeroderma pigmentosum (group A) fibroblasts have a capacity of removing these bulky adducts at least from the active genes

  3. Role of diaxial versus diequatorial hydroxyl groups in the tumorigenic activity of a benzo[a]pyrene bay-region diol epoxide.

    OpenAIRE

    Chang, R L; Wood, A.W.; Conney, A H; Yagi, H.; Sayer, J M; Thakker, D R; Jerina, D M; Levin, W

    1987-01-01

    Tumorigenic activities of the (7R,8S,9S,10R)-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro derivatives of benzo[a]pyrene [(+)-B[a]P diol epoxide-2] and 6-fluorobenzo[a]pyrene (6-FB[a]P diol epoxide-2) were evaluated in newborn CD-1 mice. A total dose of 14 nmol of either diol epoxide was administered to preweanling mice, and tumorigenic activity was determined when the mice were 32 to 36 weeks old. At the termination of the study, 13% of solvent-treated control mice had developed lung tumors w...

  4. Myeloperoxidase - 463A variant reduces benzo(a)pyrene diol epoxide DNA adducts in skin of coal tar treated patients

    Energy Technology Data Exchange (ETDEWEB)

    Rojas, M.; Godschalk, R.; Alexandrov, K.; Cascorbi, I.; Kriek, E.; Ostertag, J.; Van Schooten, F.J.; Bartsch, H. [German Cancer Research Center, Heidelberg (Germany). Div. of Toxicology & Cancer Risk Factors

    2001-07-01

    The skin of atopic dermatitis patients provides an excellent model to study the role of inflammation in benzo(a)pyrene (BaP) activation, since these individuals are often topically treated with ointments containing high concentrations of BaP. The authors determined, by HPLC with fluorescence detection, the BaP diol epoxide (BPDE)-DNA adduct levels in human skin after topical treatment with coal tar and their modulation by the -453G into A myeloperoxidase (MPO) polymorphism, which reduces MPO mRNA expression. The data show for the first time: (i) the in vivo formation of BPDE-DNA adducts in human skin treated with coal tar; (ii) that the MPO-463AA/AG genotype reduced BPDE-DNA adduct levels in human skin.

  5. BENZO(A)PYRENE DIOL EPOXIDE I BINDS TO DNA AT REPLICATION FORKS (JOURNAL VERSION)

    Science.gov (United States)

    The distribution in replication forks of DNA lesions caused by the treatment of S phase calls with benzo(a)pyrene-diol-epoxide-1 (BPDE-1) was studied in synchronized C3H10T1/2 cells. Sites of carcinogen modification of DNA were identified by polyclonal rabbit antibodies that were...

  6. Mechanism of the inhibition of mutagenicity of a benzo[a]pyrene 7,8-diol 9,10-epoxide by riboflavin 5'-phosphate.

    OpenAIRE

    Wood, A.W.; Sayer, J M; Newmark, H L; Yagi, H.; Michaud, D P; Jerina, D M; Conney, A H

    1982-01-01

    Riboflavin 5'-phosphate (flavin mononucleotide; FMN) inhibits the mutagenicity of (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P diol epoxide), the only known ultimate carcinogenic metabolite of benzo[a]pyrene. Coincubation of 10, 25, and 50 nmol of FMN with strain TA100 of histidine-dependent Salmonella typhimurium inhibits the mutagenicity of 0.05 nmol of the diol epoxide by 50, 70, and 90%, respectively. Ribose 5-phosphate and riboflavin sh...

  7. Illegitimate recombination induced by benzo[a]pyrene diol epoxide in Escherichia coli

    International Nuclear Information System (INIS)

    Duplex DNA oligomer constructs (32 base pairs) were paired that contained a single benzo[a]pyrene (BP) adduct at a specific deoxyadenosine or deoxyguanosine site in either one or both strands. These constructs were inserted into M13 replicative form viral DNA, and the DNA from progeny virus generated by transfection of Escherichia coli was examined by sequence analysis at the site of oligomer insertion. With nonalkylated constructs, and with constructs containing only one BP adduct, no sequence alterations were found in progeny viral DNAs. With constructs containing two BP adducts, one in each strand and closely spaced, some progeny DNAs showed the original oligomer sequence, whereas others exhibited large deletions and illegitimate (non-homologous) recombination, both of which removed the damage construct. Increasing the distance between BP adducts in the construct reduced the frequency of recombinant events. These sequence alterations occurred in both recA+ and recA- host cells. The authors speculate that the closely spaced adducts in opposite construct strands cause a rare distortion in DNA structure, which activates the recombinant machinery, and that mutagenic and carcinogenic agents other than polycyclic aromatic hydrocarbons may cause similar DNA distortions, which induce illegitimate recombination

  8. BENZO[A]PYRENE AND ITS K-REGION DIOL INDUCE DNA DAMAGE IN C3H10T1/2C18 CELLS AS MEASURED BY THE ALKALINE SINGLE CELL GEL (COMET) ASSAY

    Science.gov (United States)

    160. Benzo[a]pyrene and its K-region diol induce DNA damage in C3HlOTl/2Cl8 cells as measured by the alkaline single cell gel (Comet) assay In a continuing series of studies on the genotoxicity ofK-region dihydrodiols of polycyclic aromatic hydrocarbons, we have repo...

  9. DNA polymerase eta participates in the mutagenic bypass of adducts induced by benzo[a]pyrene diol epoxide in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Alden C Klarer

    Full Text Available Y-family DNA-polymerases have larger active sites that can accommodate bulky DNA adducts allowing them to bypass these lesions during replication. One member, polymerase eta (pol eta, is specialized for the bypass of UV-induced thymidine-thymidine dimers, correctly inserting two adenines. Loss of pol eta function is the molecular basis for xeroderma pigmentosum (XP variant where the accumulation of mutations results in a dramatic increase in UV-induced skin cancers. Less is known about the role of pol eta in the bypass of other DNA adducts. A commonly encountered DNA adduct is that caused by benzo[a]pyrene diol epoxide (BPDE, the ultimate carcinogenic metabolite of the environmental chemical benzo[a]pyrene. Here, treatment of pol eta-deficient fibroblasts from humans and mice with BPDE resulted in a significant decrease in Hprt gene mutations. These studies in mammalian cells support a number of in vitro reports that purified pol eta has error-prone activity on plasmids with site-directed BPDE adducts. Sequencing the Hprt gene from this work shows that the majority of mutations are G>T transversions. These data suggest that pol eta has error-prone activity when bypassing BPDE-adducts. Understanding the basis of environmental carcinogen-derived mutations may enable prevention strategies to reduce such mutations with the intent to reduce the number of environmentally relevant cancers.

  10. Serum Level of Antibody against Benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA Adducts in People Dermally Exposed to PAHs

    Directory of Open Access Journals (Sweden)

    Lenka Borska

    2014-01-01

    Full Text Available Some specific antibodies indicate the presence of antigenic structures on DNA (DNA adducts that can play an important role in the process of mutagenesis and/or carcinogenesis. They indicate the presence of increased genotoxic potential (hazard prior to the formation of disease (primary prevention. The present study was focused on the serum level of benzo[a]pyrene 7,8-diol-9,10-epoxide-DNA adducts antibodies (anti-BPDE-DNA in psoriatic patients (n=55 dermally exposed to different levels of polycyclic aromatic hydrocarbons (PAHs. The general goal of the study was to contribute to better understanding of the value of the assumed biomarker (anti-BPDE-DNA for evaluation of the organism's answer to genotoxic exposure to PAHs. Elevated level of exposure to PAHs resulted in the increased level of anti-BPDE-DNA. However, almost all levels of anti-BPDE-DNA ranged within the field of low values. Both variants of GT (CCT-3% and CCT-5% induced higher expression of anti-BPDE-DNA in the group of nonsmokers. Significant relations between the level of anti-BPDE-DNA and PASI score, total duration of the therapy, or time of UVR exposure were not found. Further studies are needed to reduce interpretation uncertainty of this promising bioindicator.

  11. Preferential binding of benzo[a]pyrene diol epoxide to the linker DNA of human foreskin fibroblasts in S phase in the presence of benzamide.

    OpenAIRE

    Kurian, P.; Jeffrey, A M; Milo, G E

    1985-01-01

    Addition of benzamide (BZ) at the onset of S phase inhibited expression of the neoplastic phenotype in human foreskin fibroblasts treated in vitro with (+/-)-7 alpha,8 beta-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P diol epoxide) in early S phase. Analysis of the specific B[a]P diol epoxide-DNA adducts revealed that ca. 65% of the total adducts in BZ and non-BZ carcinogen-treated cells was the B[a]P diol epoxide-deoxyguanine adduct. Limited micrococcal nuclease di...

  12. Preferential binding of benzo[a]pyrene diol epoxide to linker DNA of human foreskin fibroblasts in S phase in the presence of benzamide

    International Nuclear Information System (INIS)

    Addition of benzamide (BZ) at the onset of S phase inhibited expression of the neoplastic phenotype of human foreskin fibroblasts treated in vitro with (+/-)-7α,8β-dihydroxy-9β,10β-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P diol epoxide) in early S phase. Analysis of the specific B[a]P diol epoxide-DNA adducts revealed that ca. 65% of the total adducts in BZ and non-BZ carcinogen-treated cells was the B[a]P diol epoxide-deoxyguanine adduct. Limited micrococcal nuclease digestion of the early S phase nuclei from cells treated with B[a]P diol epoxide indicated that the carcinogen binds equally to linker and core DNA. However, when the cells were predominantly in S phase, in the presence of BZ, there was ca. three times more binding of B[a]P diol epoxide to the linker DNA compared to the core region. These data indicate that pretreatment of the cells with BZ at the onset of S phase established a preferential binding pattern in the linker DNA similar to that observed in the cells treated with B[a]P diol epoxide in G1 arrest

  13. The role of hRev7, the accessory subunit of hPolζ, in translesion synthesis past DNA damage induced by benzo[a]pyrene diol epoxide (BPDE

    Directory of Open Access Journals (Sweden)

    Maher Veronica M

    2010-12-01

    Full Text Available Abstract Background DNA polymerase zeta (Polζ is a specialized DNA polymerase that, unlike classical replicative polymerases, is capable of replicating past DNA lesions, i.e. of performing translesion synthesis (TLS. The catalytic subunit of hPolζ, hRev3, has been shown to play a critical role in DNA damage-induced mutagenesis in human cells, but less is known about the role of hRev7, the accessory subunit of hPolζ, in such mutagenesis. To address this question, we recently generated human fibroblasts with very significantly reduced levels of hRev7 protein and demonstrated that hRev7 is required to protect cells from ultraviolet(254 nm (UV radiation-induced cytotoxicity and mutagenesis (McNally et al., DNA Repair 7 (2008 597-604. The goal of the present study was to determine whether hRev7 is similarly involved in the tolerance of DNA damage induced by benzo[a]pyrene diol epoxide (BPDE, the reactive form of the widespread environmental carcinogen benzo[a]pyrene. Methods To determine whether hRev7 also plays a role in protecting human cells from the cytotoxicity and mutagenesis induced by benzo[a]pyrene diol epoxide (BPDE, cell strains with reduced hRev7 were compared to their parental strain and a vector control strain for the effect of BPDE on cell survival, induction of mutations, and the ability to progress through the cell cycle. Results The results show that cell strains with reduced hRev7 are more sensitive to the cytotoxic effect of BPDE than the control strains, and progress through S-phase at a slower rate than the control cells following BPDE treatment, indicating that hRev7, and likely hPolζ, is required for efficient bypass of BPDE-induced DNA lesions. However, neither the frequency nor kinds of mutations induced by BPDE in cells with reduced hRev7 differ significantly from those induced in the control strains, suggesting that hPolζ is not essential for inserting nucleotides opposite BPDE-induced DNA damage. Conclusions Taken

  14. BENZO[A]PYRENE AND BENZO[C]PHENANTHRENE: THE EFFECT OF STRUCTURE ON THE BINDING OF WATER MOLECULES TO THE DIOL EPOXIDES

    Science.gov (United States)

    ABSTRACTThe interaction with water of the diol epoxides (DEs) of both a planar and a non-planar PAH have been examined using molecular dynamics. To determine probable water locations around the DE for later use in the study of DE protonation, molecular dynamics simulations u...

  15. Detection of benzo[a]pyrene diol epoxide-DNA adducts in peripheral blood lymphocytes and antibodies to the adducts in serum from coke oven workers.

    OpenAIRE

    Harris, C. C.; Vahakangas, K.; Newman, M J; Trivers, G E; Shamsuddin, A; Sinopoli, N; Mann, D L; Wright, W. E.

    1985-01-01

    Coke oven workers are exposed to high levels of carcinogenic polycyclic aromatic hydrocarbons, including benzo[a]pyrene (B[a]P), and are at increased risk of lung cancer. Since B[a]P is enzymatically activated to 7 beta,8 alpha-dihydroxy(9 alpha, 10 alpha)epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]PDE) that forms adducts with DNA, the presence of these adducts was measured in DNA from peripheral blood lymphocytes by synchronous fluorescence spectrophotometry and enzyme radioimmunoassay. App...

  16. Epigallocatechin-3-gallate reduces DNA damage induced by benzo[a]pyrene diol epoxide and cigarette smoke condensate in human mucosa tissue cultures.

    Science.gov (United States)

    Baumeister, Philipp; Reiter, Maximilian; Kleinsasser, Norbert; Matthias, Christoph; Harréus, Ulrich

    2009-06-01

    Although epidemiological studies indicate cancer preventive effects of diets rich in fruit and vegetables, large clinical intervention studies conducted to evaluate dietary supplementation with micronutrients, mostly vitamins, showed disappointing results in large parts. In contrast, there is encouraging epidemiologic data indicating great chemopreventive potential of a large group of phytochemicals, namely polyphenols. This study shows the DNA protective effect epigallocatechin-3-gallate, a tea catechin, and one of the best-studied substances within this group, on carcinogen-induced DNA fragmentation in upper aerodigestive tract cells. Cell cultures from fresh oropharyngeal mucosa biopsies were preincubated with epigallocatechin-3-gallate in different concentrations before DNA damage was introduced with the metabolically activated carcinogen benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide or cigarette smoke condensate. Effects on resulting DNA fragmentation were measured using the alkaline single-cell microgel electrophoresis (comet assay). Epigallocatechin-3-gallate significantly reduced benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-induced DNA damage by up to 51% (Pculture model. PMID:19491610

  17. Benzo[a]pyrene diol epoxide suppresses retinoic acid receptor-β2 expression by recruiting DNA (cytosine-5--methyltransferase 3A

    Directory of Open Access Journals (Sweden)

    Xu Xiao-Chun

    2010-04-01

    Full Text Available Abstract Tobacco smoke is an important risk factor for various human cancers, including esophageal cancer. How benzo [a]pyrene diol epoxide (BPDE, a carcinogen present in tobacco smoke as well as in environmental pollution, induces esophageal carcinogenesis has yet to be defined. In this study, we investigated the molecular mechanism responsible for BPDE-suppressed expression of retinoic acid receptor-beta2 (RAR-β2 in esophageal cancer cells. We treated esophageal cancer cells with BPDE before performing methylation-specific polymerase chain reaction (MSP to find that BPDE induced methylation of the RAR-β2 gene promoter. We then performed chromatin immunoprecipitation (ChIP assays to find that BPDE recruited genes of the methylation machinery into the RAR-β2 gene promoter. We found that BPDE recruited DNA (cytosine-5--methyltransferase 3 alpha (DNMT3A, but not beta (DNMT3B, in a time-dependent manner to methylate the RAR-β2 gene promoter, which we confirmed by reverse transcription-polymerase chain reaction (RT-PCR analysis of the reduced RAR-β2 expression in these BPDE-treated esophageal cancer cell lines. However, BPDE did not significantly change DNMT3A expression, but it slightly reduced DNMT3B expression. DNA methylase inhibitor 5-aza-2'-deoxycytidine (5-Aza and DNMT3A small hairpin RNA (shRNA vector antagonized the effects of BPDE on RAR-β2 expressions. Transient transfection of the DNMT3A shRNA vector also antagonized BPDE's effects on expression of RAR-β2, c-Jun, phosphorylated extracellular signal-regulated protein kinases 1/2 (ERK1/2, and cyclooxygenase-2 (COX-2, suggesting a possible therapeutic effect. The results of this study form the link between the esophageal cancer risk factor BPDE and the reduced RAR-β2 expression.

  18. Metabolic activation and DNA binding of benzo(a)pyrene in cultured human bronchus

    DEFF Research Database (Denmark)

    1977-01-01

    predominant metabolite formed by human bronchus from the (-)-trans-7,8-diol is found by high-pressure liquid chromatographic analysis to be the diol-epoxide r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahy-drobenzo(a)pyrene. The results suggest that this diol-epoxide is the major benzo(a)pyrene metabolite bound...

  19. Flow cytometric measurement of the metabolism of benzo[a]pyrene by mouse liver cells in culture

    International Nuclear Information System (INIS)

    The metabolism of benzo[a]pyrene in individual cells was monitored by flow cytometry. The measurements are based on the alterations that occur in the fluorescence emission spectrum of benzo[a]pyrene when it is converted to various metabolites. Using present instrumentation the technique could easily detect 1x106 molecules per cells of benzo[a]pyrene and 1x107 molecules per cell of the diol epoxide. The analysis of C3H IOT 1/2 mouse fibroblasts growing in culture indicated that there was heterogeneity in the conversion of the parent compound into diol epoxide derivatives suggesting that some variation in sensitivity to transformation by benzo[a]pyrene may be due to differences in cellular metabolism. The technique allows sensitive detection of metabolites in viable cells, and provides a new approach to the study of factors that influence both metabolism and transformation. (orig.)

  20. Preferential Formation of Benzo[a]pyrene Adducts at Lung Cancer Mutational Hotspots in P53

    Science.gov (United States)

    Denissenko, Mikhail F.; Pao, Annie; Tang, Moon-Shong; Pfeifer, Gerd P.

    1996-10-01

    Cigarette smoke carcinogens such as benzo[a]pyrene are implicated in the development of lung cancer. The distribution of benzo[a]pyrene diol epoxide (BPDE) adducts along exons of the P53 gene in BPDE-treated HeLa cells and bronchial epithelial cells was mapped at nucleotide resolution. Strong and selective adduct formation occurred at guanine positions in codons 157, 248, and 273. These same positions are the major mutational hotspots in human lung cancers. Thus, targeted adduct formation rather than phenotypic selection appears to shape the P53 mutational spectrum in lung cancer. These results provide a direct etiological link between a defined chemical carcinogen and human cancer.

  1. Benzo(a)pyrene diolepoxide-DNA adducts detected by synchronous fluorescence spectrophotometry.

    OpenAIRE

    Vahakangas, K.; Trivers, G; Rowe, M.; Harris, C. C.

    1985-01-01

    Using benzo(a)pyrene (BP) as a model carcinogen we are currently applying a fluorescence technique to detect the very low levels of carcinogen-DNA adducts in human populations due to environmental exposure. In synchronous fluorescence spectrophotometry for detection of BP-diol epoxide-DNA, excitation and emission wavelengths are scanned simultaneously with a fixed wavelength difference (delta lambda) of 34 nm. Compared to conventional fluorescence methods only one peak emerges because excitat...

  2. Rapid synthesis of macrocycles from diol precursors

    DEFF Research Database (Denmark)

    Wingstrand, Magnus; Madsen, Charlotte Marie; Clausen, Mads Hartvig

    2009-01-01

    A method for the formation of synthetic macrocycles with different ring sizes from diols is presented. Reacting a simple diol precursor with electrophilic reagents leads to a cyclic carbonate, sulfite or phosphate in a single step in 25-60% yield. Converting the cyclization precursor to a bis...

  3. Direct Copolymerization of CO2 and Diols

    Science.gov (United States)

    Tamura, Masazumi; Ito, Kazuki; Honda, Masayoshi; Nakagawa, Yoshinao; Sugimoto, Hiroshi; Tomishige, Keiichi

    2016-04-01

    Direct polymerization of CO2 and diols is promising as a simple and environmental-benign method in place of conventional processes using high-cost and/or hazardous reagents such as phosgene, carbon monoxide and epoxides, however, there are no reports on the direct method due to the inertness of CO2 and severe equilibrium limitation of the reaction. Herein, we firstly substantiate the direct copolymerization of CO2 and diols using CeO2 catalyst and 2-cyanopyridine promotor, providing the alternating cooligomers in high diol-based yield (up to 99%) and selectivity (up to >99%). This catalyst system is applicable to various diols including linear C4-C10 α,ω-diols to provide high yields of the corresponding cooligomers, which cannot be obtained by well-known methods such as copolymerization of CO2 and cyclic ethers and ring-opening polymerization of cyclic carbonates. This process provides us a facile synthesis method for versatile polycarbonates from various diols and CO2 owing to simplicity of diols modification.

  4. Uptake of 7,12-dimethylbenz(a)anthracene and benzo(a)pyrene in melanin-containing tissues

    Energy Technology Data Exchange (ETDEWEB)

    Roberto, A.; Larsson, B.S. [Uppsala Univ., Dept. of Pharmaceutical Biosciences, Div. of Toxicology, Uppsala (Sweden); Tjaelve, H. [The Swedish Univ. of Agricultural Sciences, Dept. of Pharmacology and Toxicology, Uppsala (Sweden)

    1996-08-01

    It is widely accepted that UV exposure is the main etiological factor for malignant melanoma. Epidemiologic studies, however, have indicated that also chemical carcinogens may be a risk factor for the disease. Polycyclic aromatic hydrocarbons such as 7,12-dimethylbenz(a)anthracene and benzo(a)pyrene represent an important class of carcinogenic chemicals. It is known that 7,12-dimethylbenz(a)anthracene can induce melanotic tumours in various animal species, and human melanocytes in culture have been found to be capable of metabolizing benzo(a)pyrene to its proximate carcinogen benzo(a)pyrene-7,8-diol. In the present study the disposition of {sup 14}C- and {sup 3}H-7,12-dimethylbenz(a)anthracene and {sup 14}C-benzo(a)pyrene was studied in pigmented and albino mice and Syrian golden hamsters by whole-body autoradiography. The results showed pronounced retention of label in the melanin-containing structures of the eyes and the hair follicles in the pigmented animals. The labelling of the corresponding structures in the albino animals was low. Additional experiments showed that 7,12-dimethylbenz(a)anthracene and benzo(a)pyrene as well as some of their metabolites are bound to melanin in vitro. The specific localization of the polycyclic aromatic hydrocarbons in pigmented tissues due to melanin affinity, combined with bioactivating capacity of melanocytes, suggest that these substances may play a role in the induction of malignant melanoma. (au).

  5. Evaluation of adjuvants for a candidate conjugate vaccine against benzo[a]pyrene.

    Science.gov (United States)

    Schellenberger, Mario T; Farinelle, Sophie; Willième, Stéphanie; Muller, Claude P

    2011-01-01

    We have recently developed an experimental vaccine based on benzo[a]pyrene (B[a]P) conjugated to tetanus toxoid as a carrier protein. In combination with Freund adjuvant, this vaccine induces high levels of B[a]P-specific antibodies to protect against detrimental effects of this carcinogen. Here we evaluate this conjugate vaccine by replacing Freund adjuvant by adjuvants that are potentially compatible with their use in humans. We showed that all adjuvants tested induced specific antibodies against B[a]P and 7,8-diol-B[a]P, its carcinogenic metabolite. The best antibody levels were obtained with Quil A, MF-59 and Alum. Biological activity in terms of enhanced retention of B[a]P was confirmed in mice immunised with Quil A, Montanide, Alum and MF-59. Our findings demonstrate that a vaccination against B[a]P is feasible in combination with adjuvants licensed in humans. PMID:21245662

  6. Mutagenicity of algal metabolites of benzo(a)pyrene for Salmonella typhimurium

    International Nuclear Information System (INIS)

    The metabolism and growth effects of benzo(a)pyrene (BaP) were studied using a freshwater green alga, Selenastrum capricornutum. Algal cultures were incubated under gold light with BaP added at concentrations of 40, 160, 400, and 1200 μg/liter for the periods of 1-4 days. The metabolites and BaP were identified and quantified from ethyl acetate extracts of both algal cells and incubation medium. The ethyl acetate extracts were evaluated for genotoxicity using a micro-volume Salmonella typhimurium forward mutation assay with resistance to 8-azaguanine for selection. This assay detected the presence of small quantities of BaP and was particularly sensitive to the mutagenicity of BaP diols. Of those extracts prepared from algae and medium from cultures exposed to 400 μg BaP/liter (10 μg/25 ml culture), only algal cell extracts from one day's growth were mutagenic. In cultures exposed to 1200 μg BaP/liter (30 μg/25 ml culture), mutagenic materials were produced or persisted in both algae and media throughout the 4-day incubation. The observed mutagenic response can be attributed in part to the presence of unmetabolized BaP or to BaP diols

  7. Induction and inhibition of benzo(a)pyrene metabolism in human epidermal keratinocytes and dermal fibroblasts

    International Nuclear Information System (INIS)

    The effects of different growth conditions and various cytochrome P-450 inducers and inhibitors were examined on the benzo(a)pyrene (BP) metabolism of human skin cells in vitro. First, three different populations of neonatal foreskin fibroblasts were treated with 0.98 μM [G-3H]-BP at 9.6 Ci/mmole for 24 hours and the organic-extractable metabolites in the extracellular, the cytoplasmic, and the nuclear fractions were analyzed by high-pressure liquid chromatography (HPLC). Confluent cultures (contact-inhibited cells), which were nontransformable, metabolized BP to a much greater extent than the transformable populations, randomly-proliferating cultures (cells in logarithmic growth) and synchronized cultures (cells treated in S phase). The major extracellular BP metabolites detected were the 9,10-diol, the 7,8-diol, and the phenols, including all four tetrols observed only in the confluent cells. From this data, the state of confluency (i.e. the model for the in vivo state of skin cells) induced enzymes which catalyze primarily the detoxification pathways leading to the formation of metabolites which are readily excreted whereas cells which are actively dividing or synchronized induced the formation of metabolites from activation pathways that led to transformation. Next, the effects of four inducers (3-methylcholanthrene (3-MCA), phenobarbital (PB), isosafrole, and Arochlor 1254) and an inhibitor (butylated hydroxyanisole (BHA)) on the BP metabolism of human epidermal keratinocytes were evaluated

  8. Rhenium-Catalyzed Deoxydehydration of Diols and Polyols

    DEFF Research Database (Denmark)

    Dethlefsen, Johannes Rytter; Fristrup, Peter

    2015-01-01

    heniumcatalyzeddeoxydehydration (DODH) of a vicinal diol into analkene; this is a model system for abundant polyols like glyceroland sugar alcohols. The present contribution includesa review of early investigations of stoichiometric reactions involvingrhenium, diols, and alkenes followed by a discussion ofthe various catalytic...... systems that have been developed withemphasis on the nature of the reductant, the substrate scope,and mechanistic investigations....

  9. Synthesis and complexation characteristics of phenanthroline and bipyridine diols

    NARCIS (Netherlands)

    Koning, B.; Boer, J.W. de; Meetsma, A.; Kellogg, R.M.

    2004-01-01

    Neocuproine (2,9-dimethyl-1,10-phenanthroline) 1 was converted to achiral and chiral tetradentate phenanthroline diols 3a-c by addition to benzophenone, adamantanone and camphor, respectively. Analogously 6,6'-dimethyl-2,2'-bipyridine 2 was converted to diol 7a on base-induced addition to benzopheno

  10. Gene expression profiles and genetic damage in benzo(a)pyrene diol epoxide-exposed TK6 cells

    International Nuclear Information System (INIS)

    Microarray analysis is a powerful tool to identify the biological effects of drugs or chemicals on cellular gene expression. In this study, we compare the relationships between traditional measures of genetic toxicology and mutagen-induced alterations in gene expression profiles. TK6 cells were incubated with 0.01, 0.1, or 1.0 μM ±anti-benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide (BPDE) for 4 h and then cultured for an additional 20 h. Aliquots of the exposed cells were removed at 4 and 24 h in order to quantify DNA adduct levels by 32P post-labeling and measure cell viability by cloning efficiency and flow cytometry. Gene expression profiles were developed by extracting total RNA from the control and exposed cells at 4 and 24 h, labeling with Cy3 or Cy5 and hybridizing to a human 350 gene array. Mutant frequencies in the Thymidine Kinase and Hypoxanthine Phosphoribosyl Transferase genes were also determined. The 10α-(deoxyguanosin-N2-yl)-7α,8β,9β-trihydroxy-7,8,9,10-tetrahydrobenzo(a) pyrene (dG-N2-BPDE) adduct increased as a function of dose and was the only adduct identified. A dose-related decrease in cell viability was evident at 24 h, but not at 4 h. Cell death occurred by apoptosis. At 4 h, analysis of the gene expression profiles revealed that Glutathione Peroxidase and Gadd45 were consistently upregulated (greater than 1.5-fold and significantly (P<0.001) greater than the control in two experiments) in response to 1.0 μM BPDE exposure. Fifteen genes were consistently down-regulated (less than 0.67-fold and significantly (P<0.001) lower than the control in two experiments) at 4 h in cultures exposed to 1.0 μM BPDE. Genes with altered expression at 4 h included genes important in the progression of the cell-cycle and those that inhibit apoptosis. At 24 h post-exposure, 16 genes, involved in cell-cycle control, detoxification, and apoptosis were consistently upregulated; 10 genes were repressed in cultures exposed to the high dose of BPDE. Real-time quantitative PCR confirmed the differential expression of selected genes. These data suggest that changes in gene expression will help to identify effects of drugs and chemicals on molecular pathways in cells, and will provide useful information about the molecular responses associated with DNA damage. Of the endpoints evaluated, DNA adduct formation was the most sensitive indicator of DNA damage. DNA adduct formation was clearly evident at low doses, but the number of genes with significantly altered expression (P<0.001) was minimal. Alterations in gene expression were more robust at doses associated with cellular toxicity and induction of mutations.

  11. Effect of heavy metals on the metabolism of benzo(a)pyrene in rats

    Energy Technology Data Exchange (ETDEWEB)

    Honey, S.A.; Yuan, Zhi-Xin; Kumar, S.; Sikka, H.C. [State Univ. of New York College, Buffalo, NY (United States)

    1996-12-31

    In order to investigate the interaction of heavy metals and PAHs, we have examined the effect of methylmercuric chloride and cadmium chloride on the oxidative metabolism by rats of benzo(a)pyrene [BaP], a model carcinogenic PAR Treatment of male rats with 2.5 or 5.0 mg/kg methylmercury (ip) reduced the rate of metabolism of BaP by liver microsomes by 38.7 and 62.2%, respectively. Cadmium was more potent than methylmercury, decreasing the rate of metabolism of BaP by 28.4, 52.2, and 69.7% by liver microsomes of rats treated with 0.5, 1.0, and 1.5 mg/kg of cadmium, respectively. The liver microsomes from animals treated with methylmercury or cadmium produced a greater proportion of BP-phenols and a lower portion of BP-diols than did the microsomes from untreated animals, suggesting that both metals also inhibit the activity of epoxide hydrase. Neither methylmercury nor cadmium had an effect on the proportion of BP-quinones formed by liver microsomes. Treatment of rats with methylmercury or cadmium did not inhibit the metabolism of BaP by liver microsomes from animals treated with 3-methylcholanthrene (3-MC) prior to metal administration, suggesting that 3-MC treatment protects against the effect of methylmercury or cadmium on the oxidative metabolism of BaP.

  12. Free radicals of benzo(a)pyrene and derivatives.

    OpenAIRE

    Sullivan, P D

    1985-01-01

    The evidence for biological involvement, the spectroscopic properties (especially EPR), and the reactions, of free radicals derived from benzo(a)pyrene and its methylated, hydroxylated, and fluorinated derivatives are reviewed.

  13. DFT Study of the Molybdenum-Catalyzed Deoxydehydration of Vicinal Diols

    DEFF Research Database (Denmark)

    Lupp, Daniel; Christensen, Niels Johan; Dethlefsen, Johannes Rytter; Fristrup, Peter

    2015-01-01

    The mechanism of the molybdenum-catalyzed deoxydehydration (DODH) of vicinal diols has been investigated using density functional theory. The proposed catalytic cycle involves condensation of the diol with an MoVI oxo complex, oxidative cleavage of the diol resulting in an MoIV complex, and extru...

  14. Peroxidatic oxidation of benzo(a)pyrene and prostaglandin biosynthesis

    International Nuclear Information System (INIS)

    The arachidonic acid dependent oxidation of benzo[a]pyrene to a mixture of 3,6-, 1,6-, and 6,12-quinones has been studied by using enzyme preparations from sheep seminal vesicles. Maximal oxidation is observed at 100 μM benzo[a]pyrene and 150 μM arachiodinic acid. The arachidonic acid dependent oxidation is peroxidatic and utilizes prostaglandin G2 (PGG2), generated in situ from arachidonate, as the hydroperoxide substrate. 15-Hydroperoxy-5,8,11,13-eicosatetraenoic acid is equivalent to PGG2 as a hydroperoxide substrate, but hydrogen peroxide, cumene hydroperoxide, and tert-butyl hydroperoxide are much poorer substrates. Arachidonic acid dependent benzo[a]pyrene oxidation by microsomal and solubilized enzyme preparations is markedly stimulated by a variety of hemes and heme proteins. This is not due to the previously reported heme stimulation of prostaglandin biosynthesis [Yoshimoto, A., Ito, H., and Tomita, K. (1970) J. Biochem. (Tokyo) 68, 487-499]. Instead, the hemes function directly as peroxidases utilizing fatty acids hydroperoxides as substrates. The incubation of PGG2 with commercial methemoglobin in the absence of any other protein gives rise to significant benzo[a]pyrene oxidation to quinones. The widespread occurrence of heme proteins in animal tissue suggests that the peroxidatic oxidation of benzo[a]pyrene will be significant in any tissue that makes appreciable concentrations of fatty acid hydroperoxides

  15. Alterations in the metabolism of benzo(a)pyrene in syrian hamster embryo (SHE) cells pretreated with phenolic antioxidants

    Energy Technology Data Exchange (ETDEWEB)

    Strniste, G.F.; Okinaka, R.T.; Chen, D.J.

    1983-01-01

    Inhibition of chemical- or raddiation-induced neoplasia has been observed in animals whose diets were supplemented with antioxidants commonly used as food additives. Inhibition of the carcinogenicity of benzo(a)pyrene (BaP) or of 7,12-dimenthylbenz(a)anthracene (DMBA) - in rats has been achieved by the addition of the phenolic antioxidants butylated hydroxyanisole (BHA) or butylated hydroxytoluene (BHT) to the diet. Our data suggest that in SHE cells antioxidants inhibit the overall metabolism of BaP to its various oxidized moieties including 7,8-diol- and 7,8,9,10-tetrol-BaP. A plausible explanation for our results with SHE cells is that the antioxidants interact directly with AHH, thus inhibiting AHH metabolic capacity. From analysis of nuclear material from SHE cells (+- antioxidants) incubated for 36 hours with BaP at 1 ..mu..g/ml, it is calculated that 4.6, 2.4 and 2.9 pmol BaP are bound to the DNA isolated from 10/sup 7/ nuclei of control, BHA-(20 ..mu..g/ml) and p-MP-(10 ..mu..g/ml) treated cultures, respectively.

  16. Metabolism and macromolecular binding of benzo(a)pyrene and its noncarcinogenic isomer benzo(e)pyrene in cell culture

    Energy Technology Data Exchange (ETDEWEB)

    Selkirk, J.K.; MacLeod, M.C.

    1978-01-01

    The carcinogenicity of the polycyclic aromatic hydrocarbon benzo(a)pyrene (B(a)P) is thought to result from the metabolic formation of a highly reactive intermediate, 7,8-dihydrodiol-9,10-oxy-B(a)P which subsequently interacts with cellular macromolecules to produce neoplasia. Evidence has been presented implicating similar bay-region diol-epoxides as the ultimate carcinogenic forms of benz(a)anthracene, 7-methyl-benz(a)anthracene, dibenz(a,h)anthracene, and chrysene. Benzo(e)pyrene (B(e)P), on the other hand, is relatively inert when tested for carcinogenicity on mouse skin and rat trachea and when tested for mutagenicity in a mammalian system. This B(e)P molecule contains two (equivalent) bay regions and quantum mechanical model calculations suggest that 9,10-dihydrodiol-11,12-oxy-B(e)P can easily form a reactive bay-region-adjacent carbonium ion. In order to explain the noncarcinogenicity of B(e)P in the context of the bay region theory, we have studied the metabolism of B(e)P by rat liver microsomes and by cultured hamster embryo fibroblasts. In both systems, the major metabolic pathways involve the K-region of B(e)P, with little or no attack on the isolated benzo ring. These results suggest that the lack of carcinogenicity of B(e)P may reflect its preferred mode of interaction with the cellular metabolic machinery.

  17. A xanthanolide diol and a dimeric xanthanolide from Xanthium species.

    Science.gov (United States)

    Ahmed, A A; Mahmoud, A A; El-Gamal, A A

    1999-06-01

    Extracts of the aerial parts of Xanthium strumarium and fruit of X. pungens afforded a new Xanthanolide diol derivative, 11alpha,13-dihydroxyxanthatin and a new dimeric xanthanolide sesquiterpene lactone, pungiolide C, in addition to some known compounds. The structures of the new compounds were determined by spectroscopic methods particularly high resolution (1)H-, (13)C-NMR and 2D (1)H- (1)H and (1)H- (13)C COSY NMR analysis. PMID:17260271

  18. The ERβ ligand 5α-androstane, 3β,17β-diol (3β-diol) regulates hypothalamic oxytocin (Oxt) gene expression.

    Science.gov (United States)

    Sharma, Dharmendra; Handa, Robert J; Uht, Rosalie M

    2012-05-01

    The endocrine component of the stress response is regulated by glucocorticoids and sex steroids. Testosterone down-regulates hypothalamic-pituitary-adrenal (HPA) axis activity; however, the mechanisms by which it does so are poorly understood. A candidate testosterone target is the oxytocin gene (Oxt), given that it too inhibits HPA activity. Within the paraventricular nucleus of the hypothalamus, oxytocinergic neurons involved in regulating the stress response do not express androgen receptors but do express estrogen receptor-β (ERβ), which binds the dihydrotestosterone metabolite 3β,17β-diol (3β-diol). Testosterone regulation of the HPA axis thus appears to involve the conversion to the ERβ-selective ligand 5α-androstane, 3β-diol. To study mechanisms by which 3β-diol could regulate Oxt expression, we used a hypothalamic neuronal cell line derived from embryonic mice that expresses Oxt constitutively and compared 3β-diol with estradiol (E2) effects. E2 and 3β-diol elicited a phasic response in Oxt mRNA levels. In the presence of either ligand, Oxt mRNA levels were increased for at least 60 min and returned to baseline by 2 h. ERβ occupancy preceded an increase in Oxt mRNA levels in the presence of 3β-diol but not E2. In tandem with ERβ occupancy, 3β-diol increased occupancy of the Oxt promoter by cAMP response element-binding protein and steroid receptor coactivator-1 at 30 min. At the same time, 3β-diol led to the increased acetylation of histone H4 but not H3. Taken together, the data suggest that in the presence of 3β-diol, ERβ associates with cAMP response element-binding protein and steroid receptor coactivator-1 to form a functional complex that drives Oxt gene expression. PMID:22434086

  19. Kinetics and mechanism of the oxidation of some diols by benzyltrimethylammonium tribromide

    Indian Academy of Sciences (India)

    Garima Goswami; Seema Kothari; Kalyan K Banerji

    2001-02-01

    The kinetics of oxidation of five vicinal and four non-vicinal diols, and two of their monoethers by benzyltrimethylammonium tribromide (BTMAB) have been studied in 3:7 (/) acetic acid-water mixture. The vicinal diols yield the carbonyl compounds arising out of the glycol bond fission while the other diols give the hydroxycarbonyl compounds. The reaction is first-order with respect to BTMAB. Michaelis-Menten type kinetics is observed with respect to diol. Addition of benzyltrimethylammonium chloride does not affect the rate. Tribromide ion is postulated to be the reactive oxidizing species. Oxidation of [1,1,2,2-2H4] ethanediol shows the absence of a kinetic isotope effect. The reaction exhibits substantial solvent isotope effect. A mechanism involving a glycol-bond fission has been proposed for the oxidation of the vicinal diols. The other diols are oxidized by a hydride ion transfer to the oxidant, as are the monohydric alcohols.

  20. Synthesis and characterizations of degradable aliphatic-aromatic copolyesters from lactic acid, dimethyl terephthalate and diol: Effects of diol type and monomer feed ratio

    Directory of Open Access Journals (Sweden)

    2010-07-01

    Full Text Available Lactic acid-based aliphatic/aromatic copolyesters are synthesized to incorporate the degradability of polylactic acid and good mechanical properties of aromatic species by using polycondensation of lactic acid (LA, dimethyl terephthalate (DMT, and various diols. Effects of diol lengths and comonomer feed ratios on structure and properties of the resulting copolymers are investigated. Three types of diols with different methylene lengths are employed, i.e., ethylene glycol (EG, 1,3-propanediol (PD and 1,4-butanediol (BD. LA/DMT/diol feed ratios of 2:1:2, 1:1:2, and 1:2:4 are used in each diol system. It is found that types of the diols play an important role in the properties of the copolyester, where an increase in diol length results in an increase in the copolymers molecular weight, and a decrease in Tg, Tm and crystallinity, when a constant monomer feed ratio is employed. Monomer feed ratio also has a significant effect on properties of the copolymers, where an increase in the aromatic content leads to formation of copolymers with higher molecular weight, longer aromatic block sequence and high aromatic to aliphatic ratio in the chain structure. These, in turn, lead to an increase in Tg, Tm, crystallinity and thermal stability of the copolymer samples, and a reduction in their solubility.

  1. Influence of cell cycle on responses of MCF-7 cells to benzo[a]pyrene

    Directory of Open Access Journals (Sweden)

    Giddings Ian

    2011-06-01

    Full Text Available Abstract Background Benzo[a]pyrene (BaP is a widespread environmental genotoxic carcinogen that damages DNA by forming adducts. This damage along with activation of the aryl hydrocarbon receptor (AHR induces complex transcriptional responses in cells. To investigate whether human cells are more susceptible to BaP in a particular phase of the cell cycle, synchronised breast carcinoma MCF-7 cells were exposed to BaP. Cell cycle progression was analysed by flow cytometry, DNA adduct formation was assessed by 32P-postlabeling analysis, microarrays of 44K human genome-wide oligos and RT-PCR were used to detect gene expression (mRNA changes and Western blotting was performed to determine the expression of some proteins, including cytochrome P450 (CYP 1A1 and CYP1B1, which are involved in BaP metabolism. Results Following BaP exposure, cells evaded G1 arrest and accumulated in S-phase. Higher levels of DNA damage occurred in S- and G2/M- compared with G0/G1-enriched cultures. Genes that were found to have altered expression included those involved in xenobiotic metabolism, apoptosis, cell cycle regulation and DNA repair. Gene ontology and pathway analysis showed the involvement of various signalling pathways in response to BaP exposure, such as the Catenin/Wnt pathway in G1, the ERK pathway in G1 and S, the Nrf2 pathway in S and G2/M and the Akt pathway in G2/M. An important finding was that higher levels of DNA damage in S- and G2/M-enriched cultures correlated with higher levels of CYP1A1 and CYP1B1 mRNA and proteins. Moreover, exposure of synchronised MCF-7 cells to BaP-7,8-diol-9,10-epoxide (BPDE, the ultimate carcinogenic metabolite of BaP, did not result in significant changes in DNA adduct levels at different phases of the cell cycle. Conclusions This study characterised the complex gene response to BaP in MCF-7 cells and revealed a strong correlation between the varying efficiency of BaP metabolism and DNA damage in different phases of the cell

  2. COMPARATIVE STUDIES OF THE EFFECT OF POLYCYCLIC AROMATIC HYDROCARBON GEOMETRY ON THE HYDROLYSIS OF DIOL EPOXIDES

    Science.gov (United States)

    Comparative studies of the effect of polycyclic aromatic hydrocarbon geometry on the hydrolysis of diol epoxides The interaction of the diol epoxides (DEs) of both planar and non-planar PAHs with water have been examined using quantum mechanical and molecular dynamics. Th...

  3. Alternating polyesteramides based on 1,4-butylene terephthalamide: 2. alternating polyesteramides based on a single, linear diol (4NTm)

    NARCIS (Netherlands)

    Serrano, P.J.M.; Thuss, E.H.L.; Gaymans, R.J.

    1997-01-01

    Strictly alternating polyesteramides consisting of 1,4-butylene terephthalamide and aliphatic diols have been synthesized in the melt in the presence of a titanium catalyst. The influence of diol length on the thermal and mechanical properties was studied. Depending on its structure, the diol took p

  4. Interindividual variation in binding of benzo[a]pyrene to DNA in cultured human Bronchi

    DEFF Research Database (Denmark)

    Harris, C.C.; Autrup, Herman; Connor, R.;

    1976-01-01

    The binding of benzo[a]pyrene to DNA in cultured human bronchus was measured in specimens from 37 patients. The binding values ranged from 2 to 151 picomoles of benzo[a]pyrene per milligram of DNA with an overall mean +/- standard error of 34.2 +/- 5.2. This 75-fold interindividual variation in t...

  5. Specificity in interaction of benzo[a]pyrene with nuclear macromolecules: implication of derivatives of two dihydrodiols in protein binding

    International Nuclear Information System (INIS)

    Benzo[a]pyrene (B[a]P), 7,8-dihydroxy-7,8-dihydro-B[a]P, and 9,10-dihydroxy-9,10-dihydro-B[a]P are metabolized by hamster embryo cells to derivatives that bind to nuclear macromolecules. The selectivity for different classes of macromolecules varies depending on the compound analyzed. The ratio of DNA specific activity to protein specific activity (pmol bound/mg of macromolecules) is high (1.51) for 7,8-dihydroxy-7,8-dihydro-B[a]P, extremely low (0.03) for 9,10-dihydroxy-9,10-dihydro-B[a]P, and intermediate (0.26) for B[a]P. Histones H3 and H2A are the major targets of 7,8-dihydroxy-7,8-dihydro-B[a]P; a protein(s) with a mobility similar to that of histone H1 is heavily labeled by 9,10 dihydroxy-9,10-dihydro-B[a]P, with minor labeling of other (nonhistone) bands. The labeling pattern seen with B[a]P is a combination of the patterns seen with the two dihydrodiol metabolites studied. Analysis of the ethyl acetate-soluble metabolites suggests that hamster embryo cells produce 9,10-dihydroxy-7,8-oxy-7,8,9,10-tetrahydro-B[a]P from 9,10-dihydroxy-9,10-dihydro-B[a]P and raise the possibility that this vicinal diol epoxide is an intermediate in the binding of 9,10-dihydroxy-9,10-dihydro-B[a]P to nuclear proteins. The differences seen suggest that factors other than the intrinsic chemical reactivity of the epoxide group are extremely important in the ineraction of potential ultimate carcinogens with biological systems

  6. Inhibition of benzopyrene-diol-epoxide (BPDE)-induced bax and caspase-9 by cadmium: Role of mitogen activated protein kinase

    International Nuclear Information System (INIS)

    Cadmium, a major metal constituent of tobacco smoke, elicits synergistic enhancement of cell transformation when combined with benzo[a]pyrene (BP) or other polynuclear aromatic hydrocarbons (PAHs). The mechanism underlying this synergism is not clearly understood. Present study demonstrates that (+/-)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), an ultimate carcinogen of BP, induces apoptosis in human leukemic HL-60 cells and others, and cadmium at non-cytotoxic concentration inhibits BPDE-induced apoptosis. We observed that BPDE treatment also activates all three MAP kinases e.g. ERK1/2, p38 and JNK in HL-60 cells, and inhibition of BPDE-induced apoptosis by cadmium is associated with down-regulation of pro-apoptotic bax induction/caspase-9 activation and up-regulation of ERK phosphorylation, whereas p38 MAP kinase and c-Jun phosphorylation (indicative of JNK activation) remain unaffected. Inhibition of ERKs by prior treatment of cells with 10 μM U0126 relieves cadmium-mediated inhibition of apoptosis/bax induction/caspase-9 activation. Our results suggest that cadmium inhibits BPDE-induced apoptosis by modulating apoptotic signaling through up-regulation of ERK, which is known to promote cell survival

  7. Synthesis, stability constants and electronic spectral studies of ternary complexes of Pr(III) with histidine and diols

    International Nuclear Information System (INIS)

    The mixed ligand complexes of the type MAB, MA2B and MaB2 where M = Pr(III), A = histidine and B = ethanediol, prop-1,2-diol, 2-butene-1, 4-diol, but-2,3-diol, pent-1,5-diol and hex-1,6-diol have been investigated by alkalimetric titrations. The overall stability constants have been evaluated at 30+1degC (μ = 0.2MKNO3). The absorption spectra of some praseodymium(III) ternary complexes in solution have been used to calculate energy interaction and intensity parameters. The low intensity of the pseudohypersensitive transition suggests higher coordination number. (author)

  8. 1-(3-Phenylisoxazol-5-ylcyclohexane-1,2-diol

    Directory of Open Access Journals (Sweden)

    Luis Astudillo

    2009-07-01

    Full Text Available In the title compound, C15H17NO3, there are two molecules in the asymmetric unit wherein the isoxazole rings make dihedral angles of 16.16 (15 and 16.79 (13° with the benzene rings, and the cyclohexane rings adopt chair conformations. In both molecules, the hydroxyl groups of the diol fragments are cis oriented, the O—C—C—O torsion angles being 60.76 (12 and −55.86 (11°. The two molecules are linked by a strong O—H...N hydrogen bond and the crystal packing is stabilized by one O—H...N and two O—H...O hydrogen bonds. An intramolecular O—H...O hydrogen bond is observed in one of the molecules.

  9. hREV3 is essential for error-prone translesion synthesis past UV or benzo[a]pyrene diol epoxide-induced DNA lesions in human fibroblasts

    International Nuclear Information System (INIS)

    In S. cerevisiae, the REV3 gene, encoding the catalytic subunit of polymerase zeta, is involved in translesion synthesis and required for the production of mutations induced by ultraviolet radiation (UV) photoproducts and other DNA fork-blocking lesions, and for the majority of spontaneous mutations. To determine whether hREV3, the human homolog of yeast REV3, is similarly involved in error-prone translesion synthesis past UV photoproducts and other lesions that block DNA replication, an hREV3 antisense construct under the control of the TetP promoter was transfected into an infinite life span human fibroblast cell strain that expresses a high level of tTAk, the activator of that promoter. Three transfectant strains expressing high levels of hREV3 antisense RNA were identified and compared with their parental cell strain for sensitivity to the cytotoxic and mutagenic effects of UV. The three hREV3 antisense-expressing cell strains were not more sensitive than the parental strain to the cytotoxic effect of UV, but the frequency of mutants induced by UV in their HPRT gene was significantly reduced, i.e. to 14% that of the parent. Two of these hREV3 antisense-expressing cell strains were compared with the parental strain for sensitivity to (±)-7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE). They were not more sensitive than the parent strain to the cytotoxic effect of BPDE, but the frequency of mutants induced was significantly reduced, i.e. in one strain, to 17% that of the parent, and in the other, to 24%. DNA sequencing showed that the kinds of mutations induced by BPDE in the parental and the derivative strains did not differ and were similar to those found previously with finite life span human fibroblasts. The data strongly support the hypothesis that hRev3 plays a critical role in the induction of mutations by UV or BPDE. Because the level of hRev3 protein in human fibroblasts is below the level of antibody detection, it was not possible to demonstrate that the decrease in mutagenesis reflected decreased hRev3 protein. However, the conclusion is supported by the fact that in a similar study with a strain expressing a high level of antisense hREV1, a very similar result was obtained, i.e. UV or BPDE mutagenesis was virtually eliminated.

  10. The roles of diol epoxide and o-quinone pathways in mouse lung tumorigenesis induced by benzo(a)pyrene: relevance to human lung carcinogenesis

    Science.gov (United States)

    There is sufficient epidemiological evidence supported by experimental data that some PAH-containing complex environmental mixtures pose risks to human health by increasing lung cancer incidence. The International Agency for Research on Cancer has determined that human respirator...

  11. Regioselective Acylation of Diols and Triols: The Cyanide Effect.

    Science.gov (United States)

    Peng, Peng; Linseis, Michael; Winter, Rainer F; Schmidt, Richard R

    2016-05-11

    Central topics of carbohydrate chemistry embrace structural modifications of carbohydrates and oligosaccharide synthesis. Both require regioselectively protected building blocks that are mainly available via indirect multistep procedures. Hence, direct protection methods targeting a specific hydroxy group are demanded. Dual hydrogen bonding will eventually differentiate between differently positioned hydroxy groups. As cyanide is capable of various kinds of hydrogen bonding and as it is a quite strong sterically nondemanding base, regioselective O-acylations should be possible at low temperatures even at sterically congested positions, thus permitting formation and also isolation of the kinetic product. Indeed, 1,2-cis-diols, having an equatorial and an axial hydroxy group, benzoyl cyanide or acetyl cyanide as an acylating agent, and DMAP as a catalyst yield at -78 °C the thermodynamically unfavorable axial O-acylation product; acyl migration is not observed under these conditions. This phenomenon was substantiated with 3,4-O-unproteced galacto- and fucopyranosides and 2,3-O-unprotected mannopyranosides. Even for 3,4,6-O-unprotected galactopyranosides as triols, axial 4-O-acylation is appreciably faster than O-acylation of the primary 6-hydroxy group. The importance of hydrogen bonding for this unusual regioselectivity could be confirmed by NMR studies and DFT calculations, which indicate favorable hydrogen bonding of cyanide to the most acidic axial hydroxy group supported by hydrogen bonding of the equatorial hydroxy group to the axial oxygen. Thus, the "cyanide effect" is due to dual hydrogen bonding of the axial hydroxy group which enhances the nucleophilicity of the respective oxygen atom, permitting an even faster reaction for diols than for mono-ols. In contrast, fluoride as a counterion favors dual hydrogen bonding to both hydroxy groups leading to equatorial O-acylation. PMID:27104625

  12. Studies on the analysis of benzo(a)pyrene and its metabolites in biological samples by using high performance liquid chromatography/fluorescence detection and gas chromatography/mass spectrometry

    International Nuclear Information System (INIS)

    An analytical method the determination of benzo(a)pyrene (BaP) and its hydroxylated metabolites, 1-hydroxybenzo(a)pyrene (1-OHBaP), 3-hydroxybenzo(a)pyrene (3-OHBaP), benzo(a)pyrene-4,5-dihydrodial(4,5-diolBaP) and benzo(a)pyrene-7,8-dihydrodiol (7,8-diolBaP), in rat urine and plasma has been developed by HPLC/FLD and GC/MS. The derivatization with alkyl iodide was employed to improve the resolution and the detection of two mono hydroxylated metabolites, 1-OHBaP and 3-OHBaP, in LC and GC. BaP and its four metabolites in spiked urine were successfully separated by gradient elution on reverse phase ODS C18 column (4.6 mm I.D., 100 mm length, particle size 5μm) using a binary mixture of MeOH/H2O (85/15, v/v) as mobile phase after ethylation at 90 .deg. C for 10 min. The extraction recoveries of BaP and its metabolites in spiked samples with liquid-liquid extraction, which was better than solid phase extraction, were in the range of 90.3-101.6% in n-hexane for urine and 95.7-106.3% in acetone for plasma, respectively. The calibration curves has shown good linearity with the correlation coefficients (R2) varying from 0.992 to 1.000 for urine and from 0.996 to 1.000 for plasma, respectively. The detection limits of all analytes were obtained in the range of 0.01-0.1 ng/mL for urine and 0.1-0.4ng/mL for plasma, respectively. The metabolites of BaP were excreted as mono hydroxy and dihydrodiol forms after intraperitoneal infection of 20 mg/kg of BaP to rats. The total amounts of BaP and four metabolites excreted in dosed rat urine were 3.79 ng over the 0 - 96 hr period from administration and the excretional recovery was less than 0.065% of the injection amounts of BaP. The proposed method was successfully applied to the determination of BaP and its hydroxylated metabolites in rat urine and plasma for the pharmacokinetic studies

  13. A screen for Benzo(apyrene in Fish Samples From Crude Oil Polluted Environments

    Directory of Open Access Journals (Sweden)

    C. Anyakora

    2008-01-01

    Full Text Available Several studies have shown that exposure to Benzo(apyrene increases the risk of cancer. In this study several fish samples from Niger the Delta region of Nigeria were screened for the presence of Benzo(apyrene. The study was carried out using Gas chromatograph coupled to a mass spectrometry detector. Benzo(apyrenes in the samples were identified through both retention time match with authentic standards and simultaneous maximization of several major ions from GC/MS data. Perylene-d12 was used as the internal standard for quantitation. Concentration of benzo(apyrene in the samples ranged from 1.47 to 10.53 µg/kg which is more than WHO recommended maximum allowable concentration. Therefore this study concludes that the population is at an elevated risk of cancer of occurrence.

  14. BENZO(A)PYRENE CONCENTRATIONS IN SOMATIC AND GONAD TISSUES OF BAY MUSSELS, 'MYTILUS EDULIS'

    Science.gov (United States)

    The purposes of the present study were to measure benzo(a)pyrene concentrations in the somatic and gonadal tissues of mytilus edulis and determine whether or not variations in those two tissue compartments could be related to seasonal fluctuations.

  15. Synthesis of an Antitumoral Diarylheptanoid Containing 1,3-Diol Functionality%Synthesis of an Antitumoral Diarylheptanoid Containing 1,3-Diol Functionality

    Institute of Scientific and Technical Information of China (English)

    张少敏; 伍贻康

    2011-01-01

    A bioactive derivative of a natural diarylheptanoid containing a 1,3-anti diol motif was synthesized with the oxygen-carrying stereogenic centers taken from an enantiopure epoxy chiral building block derived from inexpensive and readily available D-glucolactone.

  16. Toxicokinetic of benzo[a]pyrene and fipronil in female green frogs (Pelophylax kl. esculentus)

    International Nuclear Information System (INIS)

    A general consensus that an increased logKow led to an increase in xenobiotic uptake and bioaccumulation is accepted. In this study we compared the toxicokinetics of two chemically different xenobiotics, i.e. benzo[a]pyrene and fipronil in female green frogs. Surprisingly, the uptake rates and the bioconcentration factors (BCF) of the two contaminants were not predicted by their logKow. The uptake rates obtained were of the same order of magnitude for the two contaminants and the BCFs measured for fipronil were about 3-fold higher than those obtained for benzo[a]pyrene. Fipronil appeared to be more recalcitrant than benzo[a]pyrene to detoxification processes leading to the accumulation of sulfone-fipronil especially in the ovaries. This phenomenon may explain reproductive influence of this contaminant described in other studies. Detoxification processes, including metabolism and the excretion of pollutants, are of importance when considering their persistence in aquatic organisms and trying to quantify their risks. Highlights: ► The uptake of benzo[a]pyrene is 1.5–3 times higher than for fipronil. ► Fipronil was more recalcitrant than benzo[a]pyrene to detoxification processes. ► This lead to increased-bioaccumulation factors except in excretion organs. ► Amphibians can be used as biomonitors for persistent pollutants. - Fipronil is more recalcitrant than benzo[a]pyrene to detoxification processes in frog.

  17. A role for the androgen metabolite, 5alpha androstane 3beta, 17beta diol (3β-diol) in the regulation of the hypothalamo-pituitary-adrenal axis.

    Science.gov (United States)

    Handa, Robert J; Sharma, Dharmendra; Uht, Rosalie

    2011-01-01

    Activation of the hypothalamo-pituitary-adrenal (HPA) axis is a basic reaction of animals to environmental perturbations that threaten homeostasis. These responses are ultimately regulated by neurons residing within the paraventricular nucleus (PVN) of the hypothalamus. Within the PVN, corticotrophin-releasing hormone (CRH), vasopressin (AVP), and oxytocin (OT) expressing neurons are critical as they can regulate both neuroendocrine and autonomic responses. Estradiol (E2) and testosterone (T) are well known reproductive hormones; however, they have also been shown to modulate stress reactivity. In rodent models, evidence shows that under some conditions E2 enhances stress activated adrenocorticotropic hormone (ACTH) and corticosterone secretion. In contrast, T decreases the gain of the HPA axis. The modulatory role of testosterone was originally thought to be via 5 alpha reduction to the potent androgen dihydrotestosterone (DHT) and its subsequent binding to the androgen receptor, whereas E2 effects were thought to be mediated by estrogen receptors alpha (ERalpha) and beta (ERbeta). However, DHT has been shown to be metabolized to the ERbeta agonist, 5α- androstane 3β, 17β Diol (3β-Diol). The actions of 3β-Diol on the HPA axis are mediated by ERbeta which inhibits the PVN response to stressors. In gonadectomized rats, ERbeta agonists reduce CORT and ACTH responses to restraint stress, an effect that is also present in wild-type but not ERbeta-knockout mice. The neurobiological mechanisms underlying the ability of ERbeta to alter HPA reactivity are not currently known. CRH, AVP, and OT have all been shown to be regulated by estradiol and recent studies indicate an important role of ERbeta in these regulatory processes. Moreover, activation of the CRH and AVP promoters has been shown to occur by 3β-Diol binding to ERbeta and this is thought to occur through alternate pathways of gene regulation. Based on available data, a novel and important role of 3β-Diol in

  18. A Role for the Androgen Metabolite, 5alpha androstane, 3beta, 17beta Diol (3b-DIol in the regulation of the hypothalamo-pituitary-adrenal axis.

    Directory of Open Access Journals (Sweden)

    Robert James Handa

    2011-11-01

    Full Text Available Activation of the hypothalamo-pituitary-adrenal (HPA axis is a basic reaction of animals to environmental perturbations that threaten homeostasis. These responses are ultimately regulated by neurons residing within the paraventricular nucleus of the hypothalamus (PVN. Within the PVN, corticotropin-releasing hormone (CRH, vasopressin (AVP and oxytocin (OT expressing neurons are critical as they can regulate both neuroendocrine and autonomic responses. Estradiol (E2 and testosterone (T are well known reproductive hormones, however, they have also been shown to modulate stress reactivity. In rodent models, evidence shows that under some conditions E2 enhances stress activated ACTH and corticosterone secretion. In contrast, T decreases the gain of the HPA axis. The modulatory role of testosterone was originally thought to be via 5 alpha reduction to the potent androgen, dihydrotestosterone, whereas E2 effects were thought to be mediated by both estrogen receptors alpha (ERα and beta (ERβ. However, DHT has been shown to be metabolized to the ERβ agonist, 5alpha- androstane 3beta,17beta diol (3b-Diol. The actions of 3β-Diol on the HPA axis are mediated by ERbeta which inhibits the PVN response to stressors. In gonadectomized rats, ERbeta agonists reduce CORT and ACTH responses to restraint stress, an effect that is also present in wild-type but not ERbeta knockout mice. The neurobiological mechanisms underlying the actions of ERbeta to alter HPA reactivity are not currently known. CRH, AVP and OT have all been shown to be regulated by estradiol and recent studies indicate an important role of ERbeta in these regulatory processes. Moreover, activation of the CRH and AVP promoters have been shown by 3β-Diol binding to ERbeta and this is thought to be through alternate pathways of gene regulation. Based on available data, a novel and important role for 3beta Diol in the regulation of the HPA axis is suggested.

  19. A Role for the Androgen Metabolite, 5alpha Androstane 3beta, 17beta Diol (3β-Diol) in the Regulation of the Hypothalamo-Pituitary–Adrenal Axis

    Science.gov (United States)

    Handa, Robert J.; Sharma, Dharmendra; Uht, Rosalie

    2011-01-01

    Activation of the hypothalamo-pituitary–adrenal (HPA) axis is a basic reaction of animals to environmental perturbations that threaten homeostasis. These responses are ultimately regulated by neurons residing within the paraventricular nucleus (PVN) of the hypothalamus. Within the PVN, corticotrophin-releasing hormone (CRH), vasopressin (AVP), and oxytocin (OT) expressing neurons are critical as they can regulate both neuroendocrine and autonomic responses. Estradiol (E2) and testosterone (T) are well known reproductive hormones; however, they have also been shown to modulate stress reactivity. In rodent models, evidence shows that under some conditions E2 enhances stress activated adrenocorticotropic hormone (ACTH) and corticosterone secretion. In contrast, T decreases the gain of the HPA axis. The modulatory role of testosterone was originally thought to be via 5 alpha reduction to the potent androgen dihydrotestosterone (DHT) and its subsequent binding to the androgen receptor, whereas E2 effects were thought to be mediated by estrogen receptors alpha (ERalpha) and beta (ERbeta). However, DHT has been shown to be metabolized to the ERbeta agonist, 5α- androstane 3β, 17β Diol (3β-Diol). The actions of 3β-Diol on the HPA axis are mediated by ERbeta which inhibits the PVN response to stressors. In gonadectomized rats, ERbeta agonists reduce CORT and ACTH responses to restraint stress, an effect that is also present in wild-type but not ERbeta-knockout mice. The neurobiological mechanisms underlying the ability of ERbeta to alter HPA reactivity are not currently known. CRH, AVP, and OT have all been shown to be regulated by estradiol and recent studies indicate an important role of ERbeta in these regulatory processes. Moreover, activation of the CRH and AVP promoters has been shown to occur by 3β-Diol binding to ERbeta and this is thought to occur through alternate pathways of gene regulation. Based on available data, a novel and important role of 3β-Diol

  20. Experimental and DFT study of cyclodehydration and acetylation of ferrocenyl diols

    Science.gov (United States)

    Lapić, Jasmina; Višnjevac, Aleksandar; Cetina, Mario; Djaković, Senka; Vrček, Valerije; Rapić, Vladimir

    2012-07-01

    Racemic ferrocenyl diols, i.e. ferrocenyl(2-hydroxymethylphenyl)methanol (2), ferrocenyl-2-(2-hydroxymethylphenyl)ethanol (7), and ferrocenyl(2-(2-hydroxyethyl)phenyl)methanol (9) have been prepared by reduction of corresponding ketoesters using NaBH4 in a mixture EtOH and Et2O. In the course of these reactions new cyclic ethers 1-ferrocenyl-2-oxaindane (3), 3-ferrocenylisochromane (8), and 1-ferrocenylisochromane (10) have been isolated as side-products. Intramolecular cyclizations of ferrocenyl diols occur in both acidic and neutral medium. Density functional theory (BP86) calculations were used to explain the mechanism of these cyclodehydrations. Acid catalyzed reaction follows the classical SN1 mechanism, whereas the cyclodehydration in neutral medium is described as an SN2 reaction. X-ray diffraction analysis of new cyclic ether products has been performed. Monoacetates 11, 13 and 15 have been obtained in the reaction of ferrocenyl diols 2, 7, and 9, respectively, and acetic anhydride. Stereoselective acylation of racemic diols by vinyl acetate have been catalyzed by various lipases, and the best stereoselectivity has been observed for the diol 2 in the presence of Penicillium camembertii lipase.

  1. Benzo[a]pyrene and glycine N-methyltransferse Interactions: Gene expression profiles of the liver detoxification pathway

    International Nuclear Information System (INIS)

    Benzo[a]pyrene (BaP) is one of many polycyclic aromatic hydrocarbons that have been identified as major risk factors for developing various cancers. We previously demonstrated that the liver cancer susceptibility gene glycine N-methyltransferase (GNMT) is capable of binding with BaP and protecting cells from BaP-7,8-diol 9,10-epoxide-DNA adduct formation. In this study, we used a cytotoxicity assay to demonstrate that the higher expression level of GNMT, the lower cytotoxicity occurred in the cells treated with BaP. In addition, a cDNA microarray containing 7,597 human genes was used to examine gene expression patterns in BaP-treated HepG2 (a liver cancer cell line that expresses very low levels of GNMT) and SCG2-1-1 (a stable HepG2 clone that expresses high levels of GNMT) cells. The results showed that among 6,018 readable HepG2 genes, 359 (6.0%) were up-regulated more than 1.5-fold and 768 (12.8%) were down-regulated. Overexpression of GNMT in SCG2-1-1 cells resulted in the down-regulation of genes related to the detoxification, kinase/phosphatase pathways, and oncogenes. Furthermore, real-time PCR was used to validate microarray data from 21 genes belonging to the detoxification pathway. Combining both microarray and real-time PCR data, the results showed that among 89 detoxification pathway genes analyzed, 22 (24.7%) were up-regulated and 6 (6.7%) were down-regulated in BaP-treated HepG2 cells, while in the BaP-treated SCG2-1-1 cells, 12 (13.5%) were up-regulated and 26 (29.2%) were down-regulated (P < 0.001). Therefore, GNMT sequesters BaP, diminishes BaP's effects to the liver detoxification pathway and prevents subsequent cytotoxicity

  2. Persistence of urinary excretion products of benzo(a)pyrene

    International Nuclear Information System (INIS)

    Persistence of DNA-adducts has been observed in a variety of experimental circumstances and has been suggested as one potential mechanism for explaining the long-term delay before expression of proliferative disease. In this concept, a stable DNA-adduct, which is a remnant of a prior exposure in a nondividing cell, would not express the genotoxic effect until the cells were stimulated to divide, and thus explain the long-term delay in expression of cancer. An alternative view of the observation of persistent DNA-adducts, described in this communication, is the continuing replenishment of DNA adducts by formation and turnover of these adducts from exposure to a constant supply of the ultimate carcinogenic species derived from a prior exposure. It is of interest to note that virtually all experiments where ''persistent'' adducts have been observed have been high dose exposures. During the course of experiments designed to develop improved methods for detection of DNA adducts and related derivatives derived from polynuclear aromatic hydrocarbons (PAH), we observed that there was a continuous excretion of urinary derivatives of the injected benzo(a)pyrene (BaP) beyond the initial burst of detoxification. This report describes the time dependent distribution of those derivatives in blood, urine, feces, and at the site of injection. 11 refs., 5 figs., 4 tabs

  3. [Benzo(a)pyrene contamination of vegetable oils].

    Science.gov (United States)

    Jedra, Małgorzata; Starski, Andrzej; Gawarska, Halina; Sawilska-Rautenstrauch, Dorota

    2008-01-01

    Benzo(a)pyrene (B(a)P) analysis was carried out with glass chromatographic column with alumina followed by reverse phase high-performance liquid chromatography (HPLC) and spectrofluorometric detection. B(a)P level in 40 vegetable oils were as follow: from 0.11 to 0.38 microg/kg in olive; from 0.92 to 3.74 microg/kg in rape seed oils; from 0.11 to 2.25 microg/kg in sunflower oils and from 0.33 to 1.26 microg/kg in soya oils. In another investigated oils: arachide (peanut) corn, safflower, linen, hempen, sesame, pumpkin seeds, grape seeds---values from 0.10 to 1.44 microg/kg and 3.83 microg/kg in sea buckthorn oil were detected. B(a)P concentration in 4 from 40 investigated oils exceed the 2 ppb limit proposed by the European Commission. Heating of sample of oils: olive, rape, soya, linen, corn, sesame, peanut, in temp. 240 degrees C for 30 min. has not influence on decreased of B(a)P level. PMID:18807910

  4. Ruthenium(salen)-catalyzed aerobic oxidative desymmetrization of meso-diols and its kinetics.

    Science.gov (United States)

    Shimizu, Hideki; Onitsuka, Satoaki; Egami, Hiromichi; Katsuki, Tsutomu

    2005-04-20

    Chiral (nitrosyl)ruthenium(salen) complexes were found to be efficient catalysts for aerobic oxidative desymmetrization of meso-diols under photoirradiation to give optically active lactols. The scope of the applicability of this reaction ranges widely from acyclic diols to mono-cyclic diols, although fine ligand-tuning of the ruthenium(salen) complexes was required to attain high enantioselectivity (up to 93% ee). In particular, the nature of the apical ligand was found to affect not only enantioselectivity but also kinetics of the desymmetrization reaction. Spectroscopic analysis of the oxidation disclosed that irradiation of visible light is indispensable not only for dissociation of the nitrosyl ligand but also for single electron transfer from the alcohol-bound ruthenium ion to dioxygen. PMID:15826178

  5. An ab initio study of three (ethane-1,2 diol/water) complexes

    Science.gov (United States)

    Manivet, Philippe; Masella, Michel

    1998-05-01

    Three (ethane-1,2 diol/water) complexes have been studied using ab initio calculations at the MP2 level. In two complexes, the ethane-1,2 diol structure is close to its gas phase experimental structure (presence of an intramolecular hydrogen bond HB and the O-C-C-O dihedral angle is gauche) while the intramolecular HB is disrupted by the presence of a water molecule in the third ( tGg'a). Computations have shown that most of the experimental observations regarding the solvation of ethane-1,2 diol in water may be reproduced only by considering the tGg'a complex (absence of intramolecular HB, O-C-C-O dihedral angle of 72-74°), which is also more stable than the other two by 2 kcal mol -1.

  6. Thermoresponsive Polymers and Inverse Opal Hydrogels for the Detection of Diols.

    Science.gov (United States)

    Couturier, Jean-Philippe; Wischerhoff, Erik; Bernin, Robert; Hettrich, Cornelia; Koetz, Joachim; Sütterlin, Martin; Tiersch, Brigitte; Laschewsky, André

    2016-05-01

    Responsive inverse opal hydrogels functionalized by boroxole moieties were synthesized and explored as sensor platforms for various low molar mass as well as polymeric diols and polyols, including saccharides, glycopolymers and catechols, by exploiting the diol induced modulation of their structural color. The underlying thermoresponsive water-soluble copolymers and hydrogels exhibit a coil-to-globule or volume phase transition, respectively, of the LCST-type. They were prepared from oligoethylene oxide methacrylate (macro)monomers and functionalized via copolymerization to bear benzoboroxole moieties. The resulting copolymers represent weak polyacids, which can bind specifically to diols within an appropriate pH window. Due to the resulting modulation of the overall hydrophilicity of the systems and the consequent shift of their phase transition temperature, the usefulness of such systems for indicating the presence of catechols, saccharides, and glycopolymers was studied, exploiting the diol/polyol induced shifts of the soluble polymers' cloud point, or the induced changes of the hydrogels' swelling. In particular, the increased acidity of benzoboroxoles compared to standard phenylboronic acids allowed performing the studies in PBS buffer (phosphate buffered saline) at the physiologically relevant pH of 7.4. The inverse opals constructed of these thermo- and analyte-responsive hydrogels enabled following the binding of specific diols by the induced shift of the optical stop band. Their highly porous structure enabled the facile and specific optical detection of not only low molar mass but also of high molar mass diol/polyol analytes such as glycopolymers. Accordingly, such thermoresponsive inverse opal systems functionalized with recognition units represent attractive and promising platforms for the facile sensing of even rather big analytes by simple optical means, or even by the bare eye. PMID:27108735

  7. Crystallization and glass transition of the diols and aminoalcohols, according to DSC data

    Science.gov (United States)

    Solonina, I. A.; Rodnikova, M. N.; Kiselev, M. P.; Khoroshilov, A. V.

    2015-05-01

    Overcooling, crystallization, and glass transition of the diol series and aminoalcohols which are the liquids with spatial hydrogen-bond networks, which are the along with the overcooling of dioxane, dimethylsulfoxide, and acetonitrile, which do not have such networks were studied by DSC. The observed phenomena are explained by the stability of H-bond networks. It was concluded that changes in the stability of the networks in and between series of diols and aminoalcohols are due to differences between their molecular structures, the energies of their hydrogen bonds, and their network topologies.

  8. Kinetics of phosphotungstic acid catalyzed oxidation of propan-1,3-diol and butan-1,4-diol by N-chlorosaccharin

    Directory of Open Access Journals (Sweden)

    Sanjay Kumar Singh

    2011-09-01

    Full Text Available The kinetic studies of N-chlorosaccharin (NCSA oxidation of propan-1,3-diol and butan-1,4-diol have been reported in presence of phophotungstic acid and in aqueous acetic acid medium. The reactions follow first-order in NCSA and one to zero order with respect to substrate and phosphotungstic acid. Increase in the concentration of added perchloric acid increases the rate of oxidation. A negative effect on the oxidation rate is observed for solvent whereas the ionic strength does not influence the rate of reaction. Addition of the reaction product, saccharin, exhibited retarding effect. Various activation parameters have been evaluated. The products of the reactions were identified as the corresponding aldehydes. A suitable scheme of mechanism consistent with the experimental results has been proposed.

  9. Topological, functional, and dynamic properties of the protein interaction networks rewired by benzo(a)pyrene

    Energy Technology Data Exchange (ETDEWEB)

    Ba, Qian [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); Li, Junyang; Huang, Chao [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Li, Jingquan; Chu, Ruiai [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); Wu, Yongning, E-mail: wuyongning@cfsa.net.cn [Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); Wang, Hui, E-mail: huiwang@sibs.ac.cn [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); School of Life Science and Technology, ShanghaiTech University, Shanghai (China)

    2015-03-01

    Benzo(a)pyrene is a common environmental and foodborne pollutant that has been identified as a human carcinogen. Although the carcinogenicity of benzo(a)pyrene has been extensively reported, its precise molecular mechanisms and the influence on system-level protein networks are not well understood. To investigate the system-level influence of benzo(a)pyrene on protein interactions and regulatory networks, a benzo(a)pyrene-rewired protein interaction network was constructed based on 769 key proteins derived from more than 500 literature reports. The protein interaction network rewired by benzo(a)pyrene was a scale-free, highly-connected biological system. Ten modules were identified, and 25 signaling pathways were enriched, most of which belong to the human diseases category, especially cancer and infectious disease. In addition, two lung-specific and two liver-specific pathways were identified. Three pathways were specific in short and medium-term networks (< 48 h), and five pathways were enriched only in the medium-term network (6 h–48 h). Finally, the expression of linker genes in the network was validated by Western blotting. These findings establish the overall, tissue- and time-specific benzo(a)pyrene-rewired protein interaction networks and provide insights into the biological effects and molecular mechanisms of action of benzo(a)pyrene. - Highlights: • Benzo(a)pyrene induced scale-free, highly-connected protein interaction networks. • 25 signaling pathways were enriched through modular analysis. • Tissue- and time-specific pathways were identified.

  10. Topological, functional, and dynamic properties of the protein interaction networks rewired by benzo(a)pyrene

    International Nuclear Information System (INIS)

    Benzo(a)pyrene is a common environmental and foodborne pollutant that has been identified as a human carcinogen. Although the carcinogenicity of benzo(a)pyrene has been extensively reported, its precise molecular mechanisms and the influence on system-level protein networks are not well understood. To investigate the system-level influence of benzo(a)pyrene on protein interactions and regulatory networks, a benzo(a)pyrene-rewired protein interaction network was constructed based on 769 key proteins derived from more than 500 literature reports. The protein interaction network rewired by benzo(a)pyrene was a scale-free, highly-connected biological system. Ten modules were identified, and 25 signaling pathways were enriched, most of which belong to the human diseases category, especially cancer and infectious disease. In addition, two lung-specific and two liver-specific pathways were identified. Three pathways were specific in short and medium-term networks (< 48 h), and five pathways were enriched only in the medium-term network (6 h–48 h). Finally, the expression of linker genes in the network was validated by Western blotting. These findings establish the overall, tissue- and time-specific benzo(a)pyrene-rewired protein interaction networks and provide insights into the biological effects and molecular mechanisms of action of benzo(a)pyrene. - Highlights: • Benzo(a)pyrene induced scale-free, highly-connected protein interaction networks. • 25 signaling pathways were enriched through modular analysis. • Tissue- and time-specific pathways were identified

  11. Chemical consequences of long-range orbital interaction in perhydronaphtalene-1,4 diol monosulfonate esters.

    NARCIS (Netherlands)

    Orru, R.V.A.

    1994-01-01

    In this thesis the base-induced reactions of perhydronaphthalene-1,4-diol monosulfonate esters are described. These compounds undergo smoothly, typical carbocationic processes upon treatment with sodium tert -amylate in refluxing benzene. The product outcome, product ratio, and (relative) rate of th

  12. Iridium‐Catalyzed Condensation of Amines and Vicinal Diols to Substituted Piperazines

    DEFF Research Database (Denmark)

    Lorentz-Petersen, Linda Luise Reeh; Nordstrøm, Lars Ulrik Rubæk; Madsen, Robert

    2012-01-01

    is believed to involve dehydrogenation of the 1,2‐diol to the α‐hydroxy aldehyde, which condenses with the amine to form the α‐hydroxy imine. The latter rearranges to the corresponding α‐amino carbonyl compound, which then reacts with another amine followed by reduction of the resulting imine....

  13. In Situ Spectroscopic Investigation of the Rhenium-Catalyzed Deoxydehydration of Vicinal Diols

    DEFF Research Database (Denmark)

    Dethlefsen, Johannes Rytter; Fristrup, Peter

    2015-01-01

    rhenium(V) complex (the rate-limiting step), 2) condensation of the diol and the rhenium(V) complex to a rhenium(V) diolate, and 3) extrusion of the alkene accompanied by oxidation of the Re center and thus regeneration of CH3ReO3. The reaction follows zero-order kinetics initially but, unexpectedly...

  14. 211At-Rh(16-S4-diol) complex as a precursor for astatine radiopharmaceuticals

    International Nuclear Information System (INIS)

    211At is one of the most promising radionuclides in α-radioimmunotherapy (α-RIT). Unfortunately, biomolecules labeled by direct electrophilic astatination are unstable due to the rapid loss of 211At under both in vitro and in vivo conditions. The present paper describes the results of our studies on attaching At- to the rhodium(III) complex with thioether ligand: 1,5,9,13-etrathiacyclohexadecane-3,11-diol (16-S4-diol). Rh3+ was chosen as a moderately soft metal cation which should form very strong bonds with soft At- anions, but first of all because of the kinetic inertness of low spin rhodium(III) d6 complexes. The 16-S4-diol ligand was selected due to formation of stable complexes with Rh3+. The experiments related to optimization of the reaction conditions were performed with the 131I, basing on a chemical similarity of I- to At-. The experiments with 211At were then carried out under the conditions found optimal for I-. The preliminary results are promising, and indicate a possibility for astatination of biomolecules by using the 211At-Rh(16-S4-diol) complex

  15. An efficient hydrophilic interaction liquid chromatography separation of 7 phospholipid classes based on a diol column

    NARCIS (Netherlands)

    Zhu, C.; Dane, A.; Spijksma, G.; Wang, M.; Greef, J. van der; Luo, G.; Hankemeier, T.; Vreeken, R.J.

    2012-01-01

    A hydrophilic interaction liquid chromatography (HILIC) - ion trap mass spectrometry method was developed for separation of a wide range of phospholipids. A diol column which is often used with normal phase chromatography was adapted to separate different phospholipid classes in HILIC mode using a m

  16. Kinetics and mechanism of the oxidation of some vicinal and non-vicinal diols by tetrabutylammonium tribromide

    Indian Academy of Sciences (India)

    Jaya Gosain; Pradeep K Sharma

    2003-04-01

    Kinetics of oxidation of five vicinal and four non-vicinal diols, and two of their monoethers, by tetrabutylammonium tribromide (TBATB) has been studied. The vicinal diols yield products arising out of glycol-bond fission, while the non-vicinal diols produce the hydroxycarbonyl compounds. The reaction is first-order with respect to TBATB. Michaelis-Menten type kinetics is observed with respect to diols. The reaction fails to induce the polymerization of acrylonitrile. There is no effect of tetrabutylammonium chloride on the reaction rate. The proposed reactive oxidizing species is the tribromide ion. The effect of solvent composition indicates that the rate increases with increase in the polarity of the solvent. The oxidation of [1,1,2,2-2H4] ethanediol shows the absence of any primary kinetic isotope effect. Values of solvent isotope effect, (H2O)/(D2O), at 288 K for the oxidation of ethanediol, propane-1,3-diol and 3-methoxybutan-1-ol are 3.41, 0.98 and 1.02 respectively. A mechanism involving a glycol-bond fission has been proposed for the oxidation of vicinal diols. Non-vicinal diols are oxidised by a hydride-transfer mechanism, as they are monohydric alcohols.

  17. Dietary effects on the uptake of benzo[a]pyrene.

    Science.gov (United States)

    Stavric, B; Klassen, R

    1994-08-01

    It has been established that exposure to polycyclic aromatic hydrocarbons (PAHs), or more specifically benzo[a]pyrene (B[a]P), either by inhalation through cigarette smoking or by contact through occupational exposure of the lungs or skin, can result in cancerous lesions. It appears that the general population consumes more B[a]P from food than from smoking. Despite this, epidemiological studies have not implicated B[a]P from foods as a causative factor in some human cancers. This lack of an epidemiological correlation between cancer incidence and intake of dietary PAHs/B[a]P could be due to some 'protective' or 'detoxification' mechanism. Despite the abundance of literature regarding the food content of B[a]P, there are few data concerning its uptake from foods. In the present study we investigated the intestinal absorption of B[a]P from foods using bile duct cannulated rats and radioactive B[a]P. [14C]B[a]P was first added to solvents such as water, corn oil, liquid paraffin or 50% ethanol, which were the administered by gavage to rats fed diets with or without added carbon. Additionally, food polyphenols such as quercetin and chlorogenic acid were also tested for their effect on the absorption of B[a]P. The results indicated that the excretion of B[a]P in the bile was reduced by water, carbon, quercetin and chlorogenic acid but was potentiated by corn oil. To complement the in vivo studies, some in vitro tests to investigate the efficiency of B[a]P extraction from different foods using water or oil as solvents were also performed. These tests indicated that extraction of B[a]P from foods was affected by the solvent. It is postulated that reduced solubility, physical adsorption and the formation of chemical adducts between B[a]P and some food ingredients, play a sporadic, although still not well determined, role in reducing the absorption of B[a]P from the gut. The results of these studies suggest that B[a]P absorption from the intestinal tract is markedly

  18. Mechanism-based inactivation of benzo[a]pyrene hydroxylase by aryl acetylenes and aryl olefins

    International Nuclear Information System (INIS)

    A series of aryl acetylenes and aryl olefins have been examined as substrates and inhibitors of cytochrome P-450 dependent monooxgenases in liver microsomes from 5,6-benzoflavone or phenobarbital pretreated rats. 1-Ethynylpyrene, 3-ethynylperylene, 2-ethynylfluorene, methyl 1-pyrenyl acetylene, cis- and trans-1-(2-bromovinyl)pyrene, and 1-allylpyrene serve as mechanism-based irreversible inactivators (suicide inhibitors) of benzo[a]pyrene hydroxylase, while 1-vinylpyrene and phenyl 1-pyrenyl acetylene do not cause a detectable suicide inhibition of benzo[a]pyrene hydroxylase. The mechanism-based loss of benzo[a]pyrene hydroxylase caused by the aryl acetylenes is not accompanied by a corresponding loss of the P-450 content of the microsomes (suicide destruction). The suicide inhibition by these aryl acetylenes therefore does not involve covalent binding to the heme moiety of the monooxygenase. Nevertheless, in the presence of NADPH, 3H-labeled 1-ethynylpyrene becomes covalently attached to the cytochrome P-450 protein; the measured stoichiometry of binding is one 1-ethynylpyrene per P-450 heme unit. The authors conclude that the inhibition of benzo[a]pyrene hydroxylase produced by 1-ethynylpyrene may be related to the mechanism of suicide inhibition of P-450 activity by chloramphenicol rather than the mechanism of suicide destruction of P-450 previously described for acetylene and propyne

  19. The mixed diol-dithiol 2,2-bis(sulfanylmethyl)propane-1,3-diol: characterization of key intermediates on a new synthetic pathway.

    Science.gov (United States)

    Simmons, Trevor R; Pickett, Christopher J; Wright, Joseph A

    2011-01-01

    A new synthetic route to 2,2-bis(sulfanylmethyl)propane-1,3-diol, (II), is described starting from the commercially available 2,2-bis(hydroxymethyl)propane-1,3-diol. The structures of two intermediates on this route are described. 5,5-Dimethenyl-2,2-dimethyl-1,3-dioxane bis(thiocyanate) (systematic name: {[5-(cyanosulfanyl)-2,2-dimethyl-1,3-dioxan-5-yl]sulfanyl}formonitrile), C(10)H(14)N(2)O(2)S(2), (X), crystallizes in the space group P2(1)/c with no symmetry relationship between the two thiocyanate groups. There is a short intramolecular N...S contact for one thiocyanate group, while the second group is positioned such that this type of interaction is not possible. 1,3-(Hydroxymethyl)propane-1,3-diyl bis(thiocyanate), C(7)H(10)N(2)O(2)S(2), (XI), also features a single short N···S contact in the solid state. Hydrogen bonding between two molecules of compound (XI) results in the formation of dimers in the crystal, which are then linked together by a second hydrogen-bond interaction between the dimers. In addition, the structures of two intermediates from an unsuccessful alternative synthesis of (II) are reported. 2,2-Bis(chloromethyl)propane-1,3-diol, C(5)H(10)Cl(2)O(2), (VI), crystallized as an inversion twin with a minor twin fraction of 0.43 (6). It forms a zigzag structure as a result of intermolecular hydrogen bonding. The structure of 9,9-dimethyl-2,4,8,10-tetraoxa-3λ(4)-thiaspiro[5.5]undecan-3-one, C(8)H(14)O(5)S, (VII), shows evidence for a weak S···O contact with a distance of 3.2529 (11) Å. PMID:21206075

  20. Cultured mouse embryos metabolize benzo[a]pyrene during early gestation: genetic differences detectable by sister chromatid exchange.

    OpenAIRE

    Galloway, S M; Perry, P E; Meneses, J. (Julio); Nebert, D W; Pedersen, R A

    1980-01-01

    Mouse embryos explanted at 7 1/2 or 8 1/2 days of gestation were cultured in medium containing benzo[a]pyrene and supplemented with 5-bromodeoxyuridine to allow detection of sister chromatid exchanges. The murine Ah locus regulates the inducible metabolism of polycyclic hydrocarbons such as benzo[a]pyrene. A high frequency of sister chromatid exchange was induced by benzo[a]pyrene in embryos from three Ah-"responsive" inbred strains (BALB/cDub, C3H/AnfCum, and C57BL/6N); there was little or n...

  1. Asymmetric reduction of α-hydroxy aromatic ketones to chiral aryl vicinal diols using carrot enzymes system

    Institute of Scientific and Technical Information of China (English)

    Xiang Liu; Yi Wang; Hai Yan Gao; Jian He Xu

    2012-01-01

    Asymmetric reduction of α-hydroxy aromatic ketones was carried out by using carrot enzymes system,yielding corresponding chiral vicinal diols with special functional groups.The optimum reaction conditions were obtained after investigation of various influencing factors.Chiral aryl vicinal diols were produced with good yields and excellent enantiomeric excesses under appropriate conditions,Meanwhile,the steric factors and electronic effects of the substituents on the aromatic ring were shown to have an interesting influence on both yield and enantioselectivity.

  2. Percutaneous absorption of an insect repellent p-menthane-3,8-DIOL: a model for human dermal absorption.

    Science.gov (United States)

    Reifenrath, William G; Olson, James J; Vedula, Usha; Osimitz, Thomas G

    2009-01-01

    p-Menthane-3,8-diol(38DIOL) was recently introduced as a natural topical insect repellent in the commercial product "OFF! Botanicals" lotion. The objective of this study was to provide an estimate of the potential for 38DIOL systemic absorption in humans. Carbon-14-labeled 38DIOL formulated in the lotion and in an ethanol solution was applied to excised pig skin in an in vitro flow-through test system predictive of skin absorption in humans. Twenty-four hours after application, radiolabel recovered from the dermis and receptor fluid was summed to determine percent absorption. At a dose of approximately 80 microg/cm(2) of 38DIOL in the lotion, a value of 3.5 +/- 0.8% of applied dose was obtained with pig skin. The corresponding value for 38DIOL in ethanol (90 microg/cm(2)) was not significantly different (3.0 +/- 1.2%). Most of the applied dose of 38DIOL was found to evaporate from pig skin (77 +/- 8% for the lotion and 87 +/- 1% for ethanol solution), thus limiting percutaneous absorption values. For reference purposes, the pig skin absorptions of piperonyl butoxide (PBO) at 100 microg/cm(2) in isopropanol, N,N-diethyl-m-toluamide (DEET) at 500 microg/cm(2) in ethanol, and neat isododecane at 650 microg/cm(2) (in order of increasing volatility) were 15 +/- 6%, 23 +/- 3%, and 0.09 +/- 0.05% of applied dose respectively. Isododecane was lost almost exclusively from the skin surface by evaporation. For additional reference, absorptions of PBO, DEET, and 38DIOL were found to be higher with excised rat skin. PMID:19557607

  3. Polyols Prepared from Ring-Opening Epoxidized Soybean Oil by a Castor Oil-Based Fatty Diol

    OpenAIRE

    Jing Zhang; Ji Jun Tang; Jiao Xia Zhang

    2015-01-01

    Several biorenewable vegetable oil-based polyols with different molecular weights and various hydroxyl functionalities were successfully prepared by ring-opening epoxidized soybean oil with a castor oil-based fatty diol. It was found that several factors, including reaction time, reaction temperature, and molar ratios between epoxidized soybean oil and castor oil diol, affect structures and rheology behaviors of the final polyols. Proton NMR, FT-IR, GPC, and rheometry results revealed that th...

  4. Absolute Configuration Determination of Azulenyl Diols Isolated From Asymmetric Pinacol Coupling.

    Science.gov (United States)

    Dragu, Eugenia Andreea; Naubron, Jean-Valere; Hanganu, Anamaria; Razus, Alexandru C; Nica, Simona

    2015-11-01

    A convenient enantioselective approach for the pinacol coupling of 1-acetylazulene involving easily accessible (R)- or (S)-BINOLs as chiral additive is reported. This supposes the preformation of the chiral titanium-BINOL complex in 1:2 ratio and subsequent reduction with zinc when, 2,3-di(azulen-1-yl)butane-2,3-diol can be isolated in around 60% enantiomeric excess. The absolute configuration of the isolated enantiomers was assigned by comparison of the experimental and Boltzmann-weighted calculated VCD and ECD spectra and assigned as (+)-(2S;3S)-di(azulen-1-yl)butane-2,3-diol. Chirality 27:826-834, 2015. © 2015 Wiley Periodicals, Inc. PMID:26364568

  5. Antibacterial action of 2-bromo-2-nitropropane-1,3-diol (bronopol).

    OpenAIRE

    Shepherd, J A; Waigh, R D; Gilbert, P

    1988-01-01

    Patterns of growth inhibition of Escherichia coli in the presence of 2-bromo-2-nitropropane-1,3-diol (bronopol) indicate a period of biocide-induced bacteriostasis followed by growth at an inhibited rate. The length of the bacteriostatic period, but not the subsequent growth inhibition, was reduced by the addition of excess cysteine. Patterns of growth inhibition were unaffected by catalase or superoxide dismutase. The bactericidal concentrations (100 to 500 micrograms/ml) were considerably i...

  6. NMR solution structures of adducts derived from the binding of polycyclic aromatic diol epoxides to DNA

    Energy Technology Data Exchange (ETDEWEB)

    Cosman, M.; Patel, D.J. [Memorial Sloan Kettering Cancer Center, New York, NY (United States). Cellular Biochemistry and Biophysics Program; Hingerty, B.E. [Oak Ridge National Lab., TN (United States). Health and Safety Research Div.; Amin, S. [American Health Foundation, Valhalla, NY (United States); Broyde, S.; Geacintov, N.E. [New York Univ., NY (United States)

    1995-12-31

    Site-specifically modified oligonucleotides were derived from the reactions of stereoisomeric polycyclic aromatic diol epoxide metabolite model compounds with oligonucleotides of defined base composition and sequence. The NMR solution structures of ten different adducts studied so far are briefly described, and it is shown that stereochemical factors and the nature of the oligonucleotide context of the complementary strands, exert a powerful influence on the conformational features of these adducts.

  7. Colloidal and Chemical Properties of Polyesters Based on Glutamic acid and Diols of Different Nature

    OpenAIRE

    Puzko N.V.; Varvarenko S.S.; Voronov A.S.; Dron I.A.; Tarnavchyk I.T.; Nosova N.G.; Samaryk V.J.; Voronov S.A.

    2012-01-01

    The paper describes synthesis method and colloid-chemical properties of novel α-amino acid based polyesters with controllable hydrophilic-lipophillic balance. Glutamic acid and diols of different nature based polyesters were obtained via low-temperature activated polyesterefication. Such polymers are able to form micellar structures in self-stabilized water dispersion. Solubilization of water insoluble dyes Sudan and toluene in polymer water solution was studied. Due to micelle forming abilit...

  8. Preparation for Supramolecular Complexes of Chiral Diols BDPDD, DMBDPD and BINOL with Some Prochiral Compounds

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Interaction between chiral diols BDPDD, DMBDPD and BINOL with prochiral compounds was examined and some new supramolecular complexes were prepared. It was found that these chiral hosts could include prochiral guests,α,β-unsaturated compounds or piper- azinedione derivatives to give inclusion crystals in different molar ratio. Formations of these supramolecular complexes were characterized by the data of IR and 1H NMR spectra.

  9. One step synthesis of 6-oxo-cholestan-3β,5α-diol

    Energy Technology Data Exchange (ETDEWEB)

    Voisin, Maud; Silvente-Poirot, Sandrine; Poirot, Marc, E-mail: marc.poirot@inserm.fr

    2014-04-11

    Highlights: • Cholesterol-5,6-epoxides are metabolized into cholestane-3β,5α,6β-triol (CT) in cancer cells. • 6-Oxo-cholestan-3β,5α-diol (OCDO) is a putative metabolite of CT. • The one step syntheses of CT and OCDO from cholesterol are reported. • The one step syntheses of labelled CT and OCDO are reported. - Abstract: Cholesterol metabolism has been recently linked to cancer, highlighting the importance of the characterization of new metabolic pathways in the sterol series. One of these pathways is centered on cholesterol-5,6-epoxides (5,6-ECs). 5,6-ECs can either generate dendrogenin A, a tumor suppressor present in healthy mammalian tissues, or the carcinogenic cholestane-3β,5α,6β-triol (CT) and its putative metabolite 6-oxo-cholestan-3β,5α-diol (OCDO) in tumor cells. We are currently investigating the identification of the enzyme involved in OCDO biosynthesis, which would be highly facilitated by the use of commercially unavailable [{sup 14}C]-cholestane-3β,5α,6β-triol and [{sup 14}C]-6-oxo-cholestan-3β,5α-diol. In the present study we report the one-step synthesis of [{sup 14}C]-cholestane-3β,5α,6β-triol and [{sup 14}C]-6-oxo-cholestan-3β,5α-diol by oxidation of [{sup 14}C]-cholesterol with iodide metaperiodate (HIO{sub 4})

  10. Synthesis and characterization of biodegradable materials: PDLLA-(MAh-Diol)n-PDLLA copolymer

    Institute of Scientific and Technical Information of China (English)

    Jia Chen; Yuan Liang Wang; Mei Na Huang

    2007-01-01

    The novel biodegradable copolymer PDLLA-(MAH-Diol)n-PDLLA with unsaturated bond was synthesized by copolymerizing lactide and prepolymer, which was prepared by the polycondensation of maleic anhydride and poly(ethylene glycol), using ptoluene sulphonic acid as catalyst. The new copolymer has improved hydrophilicity and flexibility. The structure and properties of the novel polymers were studied by FTIR, NMR, GPC-MALLS and DSC.

  11. Tumor initiating and promoting activities of various benzo(a)pyrene metabolites in mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Slaga, T J; Bracken, W M; Viaje, A; Berry, D L; Fischer, S M; Miller, D R; Levin, W; Conney, A H; Yagi, H; Jerina, D M

    1977-01-01

    The skin tumor-initiating activities of the twelve isomeric phenols of BP revealed that 2-OHBP was as potent as BP while 11-OHBP was moderately active and the others were weak or inactive. However, 2-OHBP has not been shown to be formed from BP in the skin or any other tissue. The (-)-trans-7,8-diol of BP skin was found to be more active as a skin tumor initiator than BP suggesting that it is a proximal carcinogen. The data on carcinogenicity, mutagenicity and metabolism suggest that BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide is the ultimate carcinogenic form of BP. The skin tumor-initiating activities of the various BP metabolites correlate very well with their complete carcinogenic in mouse skin except for BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide. It was found to have skin tumor initiating activity but not complete carcinogenic activity. However, BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide was found to be a very potent complete carcinogen in newborn mice. It is possible that BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide is only a tumor initiator in which a promoting stimulus must be supplied for carcinogenic activity. A natural tumor promoting stimulus may be present in the newborn mouse. There is also a good correlation between the skin tumor initiating activities of the various BP metabolites and their mutagenic activity in the V79 mammalian cell mediated mutagenesis system.

  12. Electrochemical detection of benzo(a)pyrene and related DNA damage using DNA/hemin/nafion–graphene biosensor

    International Nuclear Information System (INIS)

    Graphical abstract: A novel electrochemical biosensor, DNA/hemin/nafion–graphene/GCE, was constructed to quantitatively study the DNA damage induced by the metabolite of benzo(a)pyrene in the presence of H2O2. - Highlights: • Construction of a novel DNA/hemin/nafion-graphene/GCE biosensor. • DNA damage induced by the benzo(a)pyrene metabolite was detected. • DPV analysis of benzo(a)pyrene provided a quantitative estimate of DNA damage. • Hemin/H2O2 system could mimic the cytochrome P450 to metabolize benzo(a)pyrene. - Abstract: A novel electrochemical biosensor, DNA/hemin/nafion–graphene/GCE, was constructed for the analysis of the benzo(a)pyrene PAH, which can produce DNA damage induced by a benzo(a)pyrene (BaP) enzyme-catalytic product. This biosensor was assembled layer-by-layer, and was characterized with the use of cyclic voltammetry, electrochemical impedance spectroscopy (EIS) and atomic force microscopy. Ultimately, it was demonstrated that the hemin/nafion–graphene/GCE was a viable platform for the immobilization of DNA. This DNA biosensor was treated separately in benzo(a)pyrene, hydrogen peroxide (H2O2) and in their mixture, respectively, and differential pulse voltammetry (DPV) analysis showed that an oxidation peak was apparent after the electrode was immersed in H2O2. Such experiments indicated that in the presence of H2O2, hemin could mimic cytochrome P450 to metabolize benzo(a)pyrene, and a voltammogram of its metabolite was recorded. The DNA damage induced by this metabolite was also detected by electrochemical impedance and ultraviolet spectroscopy. Finally, a novel, indirect DPV analytical method for BaP in aqueous solution was developed based on the linear metabolite versus BaP concentration plot; this method provided a new, indirect, quantitative estimate of DNA damage

  13. 5α-Estrane-3β,17β-diol and 5β-estrane-3α,17β-diol: definitive screening biomarkers to sign nandrolone abuse in cattle?

    Science.gov (United States)

    Dervilly-Pinel, Gaud; Rambaud, Lauriane; Sitthisack, Parina; Monteau, Fabrice; Hewitt, S Armstrong; Kennedy, D Glenn; Le Bizec, Bruno

    2011-09-01

    17β-Nandrolone (17β-NT) is one of the most frequently misused anabolic steroids in meat producing animals. As a result of its extensive metabolism combined with the possibility of interferences with other endogenous compounds, detection of its illegal use often turns out to be a difficult issue. In recent years, proving the illegal administration of 17β-NT became even more challenging since the presence of endogenous presence of 17β-NT or some of its metabolite in different species was demonstrated. In bovines, 17α-NT can occur naturally in the urine of pregnant cows and recent findings reported that both forms can be detected in injured animals. Because efficient control must both take into account metabolic patterns and associated kinetics of elimination, the purpose of the present study was to investigate further some estranediols (5α-estrane-3β,17β-diol (abb), 5β-estrane-3α,17β-diol (bab), 5α-estrane-3β,17α-diol (aba), 5α-estrane-3α,17β-diol (aab) and 5β-estrane-3α,17α-diol (baa)) as particular metabolites of 17β-NT on a large number of injured (n=65) or pregnant (n=40) bovines. Whereas the metabolites abb, bab, aba and baa have previously been detected in urine up to several days after 17β-NT administration, the present study showed that some of the isomers abb (5α-estrane-3β,17β-diol) and bab (5β-estrane-3α,17β-diol) could not be detected in injured or pregnant animals, even at very low levels. This result may open a new way for the screening of anabolic steroid administration considering these 2 estranediols as biomarkers to indicate nandrolone abuse in cattle. PMID:21621615

  14. Separation of water-soluble metabolites of benzo[a]pyrene formed by cultured human colon

    DEFF Research Database (Denmark)

    1979-01-01

    A method has been developed to separate conjugated metabolites of benzo[a]pyrene into three major fractions: sulfate esters, glucuronides and glutathione conjugates. In cultured human colon, formation of sulfate esters and glutathione conjugates is the major conjugation pathway, while formation of...... glucuronides accounts for only 6 per cent of the water-soluble metabolites. Hydrolysis of the sulfate esters with arylsulfatase and the glucuronides with β-glucuronidase released metabolites of benzo[a]pyrene that were extractable with organic solvent. Separation of these metabolites by high-pressure liquid...... chromatography indicated that trans-4,5-dihydro-4,5-dihydroxybenzo[a]pyrene,7,8,9, 10-tetrahydro-7,8,9, 10-tetrahydroxybenzo[a]pyrene and trans-9, 10-dihydro-9, 10-dihydroxybenzo[a]pyrene were the major substrates for UDP-glucuronic acid transferase, while trans-7,8-dihydro-7,8-dihydroxybenzo[a]pyrene and 9...

  15. Benzo(a)pyrene activation and detoxification by human pulmonary alveolar macrophages and lymphocytes

    International Nuclear Information System (INIS)

    Comparisons of pulmonary alveolar macrophages and circulating lymphocytes from five smokers and five nonsmokers for their ability to metabolize benzo(a)pyrene as determined by high pressure liquid chromatography were carried out. Utilizing this approach, further investigation of activation and detoxification by several human cell types could provide the basis for more precise and comprehensive studies of carcinogen and drug metabolism in the human lung, and for a better assessment of cancer risk in selected populations

  16. Bacillus subtilis is a Potential Degrader of Pyrene and Benzo[a]pyrene

    Directory of Open Access Journals (Sweden)

    Lynette Ekunwe

    2005-08-01

    Full Text Available Polycyclic Aromatic Hydrocarbons (PAHs are a group of compounds that pose many health threats to human and animal life. They occur in nature as a result of incomplete combustion of organic matter, as well as from many anthropogenic sources including cigarette smoke and automobile exhaust. PAHs have been reported to cause liver damage, red blood cell damage and a variety of cancers. Because of this, methods to reduce the amount of PAHs in the environment are continuously being sought. The purpose of this study was to find soil bacteria capable of degrading high molecular weight PAHs, such as pyrene (Pyr and benzo[a]pyrene (BaP, which contain more than three benzene rings and so persist in the environment. Bacillus subtilis, identified by fatty acid methyl ester (FAME analysis, was isolated from PAH contaminated soil. Because it grew in the presence of 33μg/ml each of pyrene, 1-AP and 1-HP, its biodegradation capabilities were assessed. It was found that after a four-day incubation period at 30oC in 20μg/ml pyrene or benzo[a]pyrene, B. subtilis was able to transform approximately 40% and 50% pyrene and benzo[a]pyrene, respectively. This is the first report implicating B. subtilis in PAH degradation. Whether or not the intermediates resulting from the transformation are more toxic than their parent compounds, and whether B. subtilis is capable of mineralizing pyrene or benzo[a]pyrene to carbon dioxide and water, remains to be evaluated.

  17. Benzo(a)pyrene inhibits the role of the bioturbator Tubifex tubifex in river sediment biogeochemistry.

    Science.gov (United States)

    Mermillod-Blondin, F; Foulquier, A; Gilbert, F; Navel, S; Montuelle, B; Bellvert, F; Comte, G; Grossi, V; Fourel, F; Lecuyer, C; Simon, L

    2013-04-15

    The interactions between invertebrates and micro-organisms living in streambed sediments often play key roles in the regulation of nutrient and organic matter fluxes in aquatic ecosystems. However, benthic sediments also constitute a privileged compartment for the accumulation of persistent organic pollutants such as PAHs or PCBs that may affect the diversity, abundance and activity of benthic organisms. The objective of this study was to quantify the impact of sediment contamination with the PAH benzo(a)pyrene on the interaction between micro-organisms and the tubificid worm, Tubifex tubifex, which has been recognized as a major bioturbator in freshwater sediments. Sedimentary microcosms (slow filtration columns) contaminated or not with benzo(a)pyrene (3 tested concentrations: 0, 1 and 5 mg kg(-1)) at the sediment surface were incubated under laboratory conditions in the presence (100 individuals) or absence of T. tubifex. Although the surface sediment contaminations with 1 mg kg(-1) and 5 mg kg(-1) of benzo(a)pyrene did not affect tubificid worm survival, these contaminations significantly influenced the role played by T. tubifex in biogeochemical processes. Indeed, tubificid worms stimulated aerobic respiration, denitrification, dehydrogenase and hydrolytic activities of micro-organisms in uncontaminated sediments whereas such effects were inhibited in sediments polluted with benzo(a)pyrene. This inhibition was due to contaminant-induced changes in bioturbation (and especially bio-irrigation) activities of worms and their resulting effects on microbial processes. This study reveals the importance of sublethal concentrations of a contaminant on ecological processes in river sediments through affecting bioturbator-microbe interactions. Since they affect microbial processes involved in water purification processes, such impacts of sublethal concentrations of pollutants should be more often considered in ecosystem health assessment. PMID:23500821

  18. Mutagenicity and tumorigenicity of the four enantiopure bay-region 3,4-diol-1,2-epoxide isomers of dibenz[a,h]anthracene

    OpenAIRE

    Chang, Richard L.; Wood, Alexander W.; Huang, Mou Tuan; Xie, Jian Guo; Cui, Xiao Xing; Reuhl, Kenneth R.; Boyd, D. R.; Lin, Yong; Shih, Weichung Joe; Balani, Suresh K.; Yagi, Haruhiko; Jerina, Donald M.; Conney, Allan H.

    2013-01-01

    Each enantiomer of the diastereomeric pair of bay-region dibenz[a,h]anthracene 3,4-diol-1,2-epoxides in which the benzylic 4-hydroxyl group and epoxide oxygen are either cis (isomer 1) or trans (isomer 2) were evaluated for mutagenic activity. In strains TA 98 and TA 100 of Salmonella typhimurium, the diol epoxide with (1S,2R,3S,4R) absolute configuration [(–)-diol epoxide-1] had the highest mutagenic activity. In Chinese hamster V-79 cells, the diol epoxide with (1R,2S,3S,4R) absolute con...

  19. Biosynthesis of unnatural bacteriochlorophyll c derivatives esterified with α,ω-diols in the green sulfur photosynthetic bacterium Chlorobaculum tepidum.

    Science.gov (United States)

    Nishimori, Risato; Mizoguchi, Tadashi; Tamiaki, Hitoshi; Kashimura, Shigenori; Saga, Yoshitaka

    2011-09-13

    Unnatural bacteriochlorophyll (BChl) c derivatives possessing a hydroxy group at the terminus of a hydrocarbon chain at the 17-propionate were biosynthesized in the green sulfur photosynthetic bacterium Chlorobaculum tepidum. Addition of exogenous 1,8-octanediol, 1,12-dodecanediol, and 1,16-hexadecanediol in acetone to liquid cultures resulted in accumulation of BChl c monoesterified with the corresponding diols. The relative ratios of the novel BChl c derivatives esterified with 1,8-, 1,12-, and 1,16-diols to totally producing BChl c were 8.2, 50.2, and 57.6% in the cells grown with additive α,ω-diols at concentrations of 1.5, 0.06, and 0.06 mM, respectively, at the final concentration. The homologue composition of BChl c derivatives esterified with these α,ω-diols was similar to that of original, coexisting BChl c esterified with farnesol (BChl c(F)), suggesting that esterification of α,ω-diols occurred at the last step of the BChl c biosynthetic pathway by BChl c synthase, BchK, in the same manner as in BChl c(F). Chlorosomes, which were isolated from cells grown in the presence of exogenous α,ω-diols, contained a ratio and a composition of BChl c derivatives esterified with the diols similar to those in the whole cells, indicating that these BChl c derivatives were actually present in chlorosomes. Q(y) absorption bands of C. tepidum cells containing the novel BChl c derivatives were shifted to a shorter wavelength, although their bandwidths were analogous to those of cells obtained by normal cultivation. Circular dichroism spectra of cells that had BChl c derivatives esterified with α,ω-diols exhibited S-shaped signals in the Q(y) region, whose polarities were the reverse of those of cells grown in the normal medium and by supplementation with neat acetone as a control experiment. These spectral features of C. tepidum possessing BChl c derivatives esterified with α,ω-diols imply that the novel BChl c derivatives possessing a hydroxy group at the

  20. Analyses of effects of α-cembratrien-diol on cell morphology and transcriptome of Valsa mali var. mali.

    Science.gov (United States)

    Yan, Ning; Du, Yongmei; Liu, Xinmin; Zhang, Hongbo; Liu, Yanhua; Shi, John; Xue, Sophia Jun; Zhang, Zhongfeng

    2017-01-01

    The objective of this work was to study the underlying mechanisms of growth inhibition of Valsa mali var. mali, the causative pathogen of apple tree canker disease, by α-cembratrien-diol. The half maximal inhibitory concentration of α-cembratrien-diol against V. mali var. mali is 18.0mg/L. Treatment of V. mali var. mali with α-cembratrien-diol resulted in various mycelial and cellular abnormalities, and the up- and down-regulation of 94 and 170 differentially expressed genes, respectively. Gene Ontology term enrichment analysis revealed that α-cembratrien-diol substantially altered the expression of genes involved in the redox process, tetrapyrrole binding, coenzyme binding, heme binding, and iron binding. Kyoto Encyclopedia of Genes and Genomes enrichment analysis also showed significant enrichment of specific metabolic pathways involving the set of differentially expressed genes. The present study will assist in the development of alternative α-cembratrien-diol-based biological control agents and ultimately facilitate organic apple production. PMID:27507455

  1. Immunogenicity of a promiscuous T cell epitope peptide based conjugate vaccine against benzo[a]pyrene: redirecting antibodies to the hapten.

    Directory of Open Access Journals (Sweden)

    Mario T Schellenberger

    Full Text Available The prototype polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P is an environmental pollutant and food contaminant of epidemiological importance. To protect against adverse effects of this ubiquitous carcinogen, we developed an immunoprophylactic strategy based on a B[a]P-protein conjugate vaccine to induce B[a]P specific antibodies (Grova et al., Vaccine. 2009;27:4142-51. Here, we investigated in mice the efficacy of B[a]P-peptide conjugates based on promiscuous T cell epitopes (TCE into further improve this approach. We showed that B[a]P-peptide conjugates induced very different levels of hapten-specific antibodies with variable functional efficacy, depending on the carrier. In some cases peptide carriers induced a more efficient antibody response against B[a]P than tetanus toxoid as a protein carrier, with the capacity to sequester more B[a]P in the blood. Reducing the carrier size to a single TCE can dramatically shift the antibody bias from the carrier to the B[a]P. Conjugates based on the TCE FIGITEL induced the best anti-hapten response and no antibodies against the carrier peptide. Some peptide conjugates increased the selectivity of the antibodies for the activated metabolite 7,8-diol-B[a]P and B[a]P by one or two orders of magnitude. The antibody efficacy was also demonstrated in their ability to sequester B[a]P in the blood and modulate its faecal excretion (15-56%. We further showed that pre-existing immunity to the carrier from which the TCE was derived did not reduce the immunogenicity of the peptide conjugate. In conclusion, we showed that a vaccination against B[a]P using promiscuous TCEs of tetanus toxin as carriers is feasible even in case of a pre-existing immunity to the toxoid and that some TCE epitopes dramatically redirect the antibody response to the hapten. Further studies to demonstrate a long-term protection of an immunoprophylactic immunisation against B[a]P are warranted.

  2. Immunogenicity of a promiscuous T cell epitope peptide based conjugate vaccine against benzo[a]pyrene: redirecting antibodies to the hapten.

    Science.gov (United States)

    Schellenberger, Mario T; Grova, Nathalie; Farinelle, Sophie; Willième, Stéphanie; Revets, Dominique; Muller, Claude P

    2012-01-01

    The prototype polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P) is an environmental pollutant and food contaminant of epidemiological importance. To protect against adverse effects of this ubiquitous carcinogen, we developed an immunoprophylactic strategy based on a B[a]P-protein conjugate vaccine to induce B[a]P specific antibodies (Grova et al., Vaccine. 2009;27:4142-51). Here, we investigated in mice the efficacy of B[a]P-peptide conjugates based on promiscuous T cell epitopes (TCE) into further improve this approach. We showed that B[a]P-peptide conjugates induced very different levels of hapten-specific antibodies with variable functional efficacy, depending on the carrier. In some cases peptide carriers induced a more efficient antibody response against B[a]P than tetanus toxoid as a protein carrier, with the capacity to sequester more B[a]P in the blood. Reducing the carrier size to a single TCE can dramatically shift the antibody bias from the carrier to the B[a]P. Conjugates based on the TCE FIGITEL induced the best anti-hapten response and no antibodies against the carrier peptide. Some peptide conjugates increased the selectivity of the antibodies for the activated metabolite 7,8-diol-B[a]P and B[a]P by one or two orders of magnitude. The antibody efficacy was also demonstrated in their ability to sequester B[a]P in the blood and modulate its faecal excretion (15-56%). We further showed that pre-existing immunity to the carrier from which the TCE was derived did not reduce the immunogenicity of the peptide conjugate. In conclusion, we showed that a vaccination against B[a]P using promiscuous TCEs of tetanus toxin as carriers is feasible even in case of a pre-existing immunity to the toxoid and that some TCE epitopes dramatically redirect the antibody response to the hapten. Further studies to demonstrate a long-term protection of an immunoprophylactic immunisation against B[a]P are warranted. PMID:22666501

  3. On the mechanism of radical fragmentation of α-dioles and some of their derivatives

    International Nuclear Information System (INIS)

    Studied is the composition of radiolysis products of deluted deaerated aqueous solutions of 1.2-dimethoxyethane and some of 1.3-dioxolanes. The solutions were leached (pH 12-13) to prevent hydrolysis of both initial and final products. Cs137 was used as a source of γ-radiation. Absorbed dose rate is equal to 4x1015 eV/mlxs. On the basis of the results obtained and literary data on radical fragmentation of α-dioles a possibility of ROCHCH2OR' particle decomposition according to the coordinated mechanism is discussed

  4. Colloidal and Chemical Properties of Polyesters Based on Glutamic acid and Diols of Different Nature

    Directory of Open Access Journals (Sweden)

    Puzko N.V.

    2012-08-01

    Full Text Available The paper describes synthesis method and colloid-chemical properties of novel α-amino acid based polyesters with controllable hydrophilic-lipophillic balance. Glutamic acid and diols of different nature based polyesters were obtained via low-temperature activated polyesterefication. Such polymers are able to form micellar structures in self-stabilized water dispersion. Solubilization of water insoluble dyes Sudan and toluene in polymer water solution was studied. Due to micelle forming ability and prognosticated biodegradability to non-toxic products, obtained polymers are promising materials for formation of novel dispersed drug delivery systems.

  5. Kinetics of complexation and oxidation of ethanolamine and diols by silver(II)

    International Nuclear Information System (INIS)

    The oxidation of ethanolamine (EtA), ethylene glycol, and several other diols by Ag(II) has been studied at pH approx. 8.5. In the basic pH range, complexation of the substrate by Ag(II) has been found to take place in two steps by successive ligand uptake. Complexation rates are higher by 1 order of magnitude in the basic pH range as compared to the acidic pH range. Oxidation then takes place through intramolecular electron transfer from substrate to Ag(II) within the complex. Oxidation rates for cis- and trans-1,2-cyclohexanediols are quite similar

  6. A Facile and Efficient Synthesis of (15R)-Latanoprost from Chiral Precursor Corey Lactone Diol

    Indian Academy of Sciences (India)

    K Vijendhar; B Srinivas; Sathyanarayana Boodida

    2015-11-01

    An efficient asymmetric synthetic route for the synthesis of anti-glaucoma agent, (15R)-latanoprost using Corey lactone diol as chiral substrate under Swern oxidation, allylic reduction and Wittig reaction conditions has been developed. In this method, reduction of keto and alkene functional groups has been achieved in a single step using low cost catalyst NiCl2/NaBH4 in methanol. This new synthetic protocol is a good alternative for the synthesis of latanoprost with high stereo selectivity and improved yield.

  7. Synthesis and characterization of segmented polyurethanes based on amphiphilic polyether diols.

    Science.gov (United States)

    Lan, P N; Corneillie, S; Schacht, E; Davies, M; Shard, A

    1996-12-01

    Segmented polyurethanes (SPUs) based on polyethylene glycol (PEG), polypropylene glycol (PPG) and a series of Pluronics with different ethylene oxide/propylene oxide ratios (EO/PO) and molecular weights were prepared. Different diisocyanates were used for making SPUs: 4,4-diphenylmethane diisocyanate (MDI), 4,4-dicyclohexylmethane diisocyanate (MDCI), hexamethylene diisocyanate (HMDI) and isophorone diisocyanate (IPDI). 1,4-Butane diol (BD) and ethylene diamine (ED) were used as chain extenders. The polymers obtained were characterized by infrared spectroscopy (IR), nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC). The microphase morphology (phase separation and phase mixing) is discussed in more detail. PMID:8968523

  8. 2-[(5-Chloro-2-oxidobenzylideneazaniumyl]-2-methylpropane-1,3-diol

    Directory of Open Access Journals (Sweden)

    Dong-Yue Wang

    2012-02-01

    Full Text Available The title compound, C11H14ClNO3, was prepared by the condensation of equimolar quantities of 5-chlorosalicylaldehyde and 2-amino-2-methylpropane-1,3-diol in methanol. In the crystal, it exists in the zwitterionic form, with nominal proton transfer from the phenol group to the imine N atom. This results in the formation of an intramolecular N—H...O hydrogen bond, which generates an S(6 ring. Intermolecular O—H...O hydrogen bonds arise from the hydroxy groups, forming (001 sheets.

  9. An asymmetric route to 2,3-epoxy-syn-1,4-cyclohexane diol derivatives using ring closing metathesis (RCM)

    Indian Academy of Sciences (India)

    Soumitra Maity; Subrata Ghosh

    2010-11-01

    An asymmetric route for the synthesis of highly functionalized 2,3-epoxy-syn-1,4-cyclohexane diol derivatives present in some polyketide natural products has been developed. The key step involves RCM of an appropriately constructed 1,7-dienol derived from D-mannitol to cyclohexane-1,4-diol followed by its stereoselective epoxidation.

  10. 6-Methyl-1,3,5-triazine-2,4-diamine butane-1,4-diol monosolvate

    Directory of Open Access Journals (Sweden)

    Rajni M. Bhardwaj

    2012-12-01

    Full Text Available The title co-crystal, C4H7N5·C4H10O2, crystallizes with one molecule of 6-methyl-1,3,5-triazine-2,4-diamine (DMT and one molecule of butane-1,4-diol in the asymmetric unit. The DMT molecules form ribbons involving centrosymmetric R22(8 dimer motifs between DMT molecules along the c-axis direction. These ribbons are further hydrogen bonded to each other through butane-1,4-diol, forming sheets parallel to (121.

  11. Iridium- and ruthenium-catalysed synthesis of 2,3-disubstituted indoles from anilines and vicinal diols

    DEFF Research Database (Denmark)

    Tursky, Matyas; Lorentz-Petersen, Linda Luise Reeh; Olsen, L. B.;

    2010-01-01

    does not require any stoichiometric additives and only produces water and dihydrogen as byproducts. Anilines containing methyl, methoxy, chloro and fluoro substituents can participate in the cyclocondensation. Meta-substituted anilines give good regioselectivity for 6-substituted indoles, while...... unsymmetrical diols afford excellent regioselectivity for the indole isomer with an aryl or large alkyl group in the 2-position. The mechanism for the cyclocondensation presumably involves initial formation of the alpha-hydroxyketone from the diol. The ketone subsequently reacts with aniline to generate the...

  12. Determination of the level of benzo[a]pyrene in fatty foods and food supplements

    OpenAIRE

    Van Der Wielen-Hustinx, Jacqueline Claire Agnes; Jansen, John; Martena, Martijn J.; De Groot, Henk; In T Veld, Paul

    2006-01-01

    Abstract A routine method was developed for the quantification of benzo[a]pyrene (BaP) in edible oils and food supplements. BaP is often taken as an indicator of the presence of polycyclic aromatic hydrocarbons. The method consists of on-line LC-clean up followed by injection to an HPLC-system connected with fluorescence detection. The method has good performance characteristics and gave good results in proficiency tests. From 2002 to 2004 about 1350 samples, oils and food supp...

  13. The Cigarette Smoke Carcinogen Benzo[a]pyrene Enhances Human Papillomavirus Synthesis▿

    OpenAIRE

    Alam, Samina; Conway, Michael J; Chen, Horng-Shen; Meyers, Craig

    2007-01-01

    Epidemiological studies suggest that cigarette smoke carcinogens are cofactors which synergize with human papillomavirus (HPV) to increase the risk of cervical cancer progression. Benzo[a]pyrene (BaP), a major carcinogen in cigarette smoke, is detected in the cervical mucus and may interact with HPV. Exposure of cervical cells to high concentrations of BaP resulted in a 10-fold increase in HPV type 31 (HPV31) viral titers, whereas treatment with low concentrations of BaP resulted in an increa...

  14. Electrochemical detection of benzo(a)pyrene and related DNA damage using DNA/hemin/nafion–graphene biosensor

    Energy Technology Data Exchange (ETDEWEB)

    Ni, Yongnian, E-mail: ynni@ncu.edu.cn [State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047 (China); Department of Chemistry, Nanchang University, Nanchang 330031 (China); Wang, Pingping; Song, Haiyan [Department of Chemistry, Nanchang University, Nanchang 330031 (China); Lin, Xiaoyun [State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047 (China); Department of Chemistry, Nanchang University, Nanchang 330031 (China); Kokot, Serge, E-mail: s.kokot@qut.edu.au [School of Chemistry, Physics and Mechanical Engineering, Science and Engineering Faculty, Queensland University of Technology, Brisbane 4001 (Australia)

    2014-04-01

    Graphical abstract: A novel electrochemical biosensor, DNA/hemin/nafion–graphene/GCE, was constructed to quantitatively study the DNA damage induced by the metabolite of benzo(a)pyrene in the presence of H{sub 2}O{sub 2}. - Highlights: • Construction of a novel DNA/hemin/nafion-graphene/GCE biosensor. • DNA damage induced by the benzo(a)pyrene metabolite was detected. • DPV analysis of benzo(a)pyrene provided a quantitative estimate of DNA damage. • Hemin/H{sub 2}O{sub 2} system could mimic the cytochrome P450 to metabolize benzo(a)pyrene. - Abstract: A novel electrochemical biosensor, DNA/hemin/nafion–graphene/GCE, was constructed for the analysis of the benzo(a)pyrene PAH, which can produce DNA damage induced by a benzo(a)pyrene (BaP) enzyme-catalytic product. This biosensor was assembled layer-by-layer, and was characterized with the use of cyclic voltammetry, electrochemical impedance spectroscopy (EIS) and atomic force microscopy. Ultimately, it was demonstrated that the hemin/nafion–graphene/GCE was a viable platform for the immobilization of DNA. This DNA biosensor was treated separately in benzo(a)pyrene, hydrogen peroxide (H{sub 2}O{sub 2}) and in their mixture, respectively, and differential pulse voltammetry (DPV) analysis showed that an oxidation peak was apparent after the electrode was immersed in H{sub 2}O{sub 2}. Such experiments indicated that in the presence of H{sub 2}O{sub 2}, hemin could mimic cytochrome P450 to metabolize benzo(a)pyrene, and a voltammogram of its metabolite was recorded. The DNA damage induced by this metabolite was also detected by electrochemical impedance and ultraviolet spectroscopy. Finally, a novel, indirect DPV analytical method for BaP in aqueous solution was developed based on the linear metabolite versus BaP concentration plot; this method provided a new, indirect, quantitative estimate of DNA damage.

  15. Ruthenium-catalysed synthesis of 2- and 3-substituted quinolines from anilines and 1,3-diols

    DEFF Research Database (Denmark)

    Monrad, Rune Nygaard; Madsen, Robert

    2011-01-01

    A straightforward synthesis of substituted quinolines is described by cyclocondensation of anilines with 1,3-diols. The reaction proceeds in mesitylene solution with catalytic amounts of RuCl3·xH 2O, PBu3 and MgBr2·OEt2. The transformation does not require any stoichiometric additives and only pr...

  16. The influence of hard segment content on dynamic mechanical properties of segmented polyurethanes based on polycarbonate diols

    Czech Academy of Sciences Publication Activity Database

    Bera, O.; Pavličević, J.; Špírková, Milena; Strachota, Adam; Poreba, Rafal; Jovičić, M.; Budinski-Simendic, J.

    Belgrade : Institute of Technical Sciences of the Serbian Academy of Sciences & Arts, 2010 - (Uskoković, D.). s. 125 [Annual Conference /12./ YUCOMAT 2010. 06.09.2010-10.09.2010, Herceg Novi] R&D Projects: GA ČR GAP108/10/0195 Institutional research plan: CEZ:AV0Z40500505 Keywords : polyurethane * polycarbonate diol Subject RIV: CD - Macromolecular Chemistry

  17. Electrocatalytic oxidation of alcohols and diols in a biphasic medium using CeIV methanesulfonate as mediator

    International Nuclear Information System (INIS)

    Some alcohols and diols were oxidized electro-catalytically in a biphasic system using cerium methanesulphonate as mediator. A mixture of methanesulphonic acid solution and benzene was used and aldehydes, ketones and diacids were some of the principal products obtained with yield varying from 27 to 98%. In several cases selectivity was obtained. (author)

  18. The introduction of a double bond on the steroid skeleton - the preparation of enol silyl ether derivatives from vicinal diols

    Czech Academy of Sciences Publication Activity Database

    Marek, Aleš; Klepetářová, Blanka; Elbert, Tomáš

    2011-01-01

    Roč. 76, č. 5 (2011), s. 443-456. ISSN 0010-0765 R&D Projects: GA AV ČR IAA400550801 Institutional research plan: CEZ:AV0Z40550506 Keywords : enol silyl ether * vicinal diol * steroids Subject RIV: CC - Organic Chemistry Impact factor: 1.283, year: 2011

  19. THE PHASE BEHAVIOR OF FLUORINATED DIOLS, DIVINYL ADIPATE, AND A FLUORINATED POLYESTER IN SUPERCRITICAL CARBON DIOXIDE. (R828131)

    Science.gov (United States)

    The use of supercritical carbon dioxide as a reaction medium for polyester synthesis is hindered by the low solubility of diols in CO2. However, it has been previously demonstrated that fluorinated compounds can exhibit greater miscibility with carbon dioxide than t...

  20. Boronate Affinity Fluorescent Nanoparticles for Förster Resonance Energy Transfer Inhibition Assay of cis-Diol Biomolecules.

    Science.gov (United States)

    Wang, Shuangshou; Ye, Jin; Li, Xinglin; Liu, Zhen

    2016-05-17

    Förster resonance energy transfer (FRET) has been essential for many applications, in which an appropriate donor-acceptor pair is the key. Traditional dye-to-dye combinations remain the working horses but are rather nonspecifically susceptive to environmental factors (such as ionic strength, pH, oxygen, etc.). Besides, to obtain desired selectivity, functionalization of the donor or acceptor is essential but usually tedious. Herein, we present fluorescent poly(m-aminophenylboronic acid) nanoparticles (poly(mAPBA) NPs) synthesized via a simple procedure and demonstrate a FRET scheme with suppressed environmental effects for the selective sensing of cis-diol biomolecules. The NPs exhibited stable fluorescence properties, resistance to environmental factors, and a Förster distance comparable size, making them ideal donor for FRET applications. By using poly(mAPBA) NPs and adenosine 5'-monophosphate modified graphene oxide (AMP-GO) as a donor and an acceptor, respectively, an environmental effects-suppressed boronate affinity-mediated FRET system was established. The fluorescence of poly(mAPBA) NPs was quenched by AMP-GO while it was restored when a competing cis-diol compounds was present. The FRET system exhibited excellent selectivity and improved sensitivity toward cis-diol compounds. Quantitative inhibition assay of glucose in human serum was demonstrated. As many cis-diol compounds such as sugars and glycoproteins are biologically and clinically significant, the FRET scheme presented herein could find more promising applications. PMID:27089186

  1. Molybdenum-catalyzed conversion of diols and biomass-derived polyols to alkenes using isopropyl alcohol as reductant and solvent

    DEFF Research Database (Denmark)

    Dethlefsen, Johannes Rytter; Lupp, Daniel; Gorfo, Ayele Teshome;

    2015-01-01

    Chemical processes capable of reducing the high oxygen content of biomass-derived polyols are in demand in order to produce renewable substitutes for chemicals of fossil origin. Deoxydehydration (DODH) is an attractive reaction that in a single step transforms a vicinal diol into an alkene, but the...

  2. Facile and Highly Diastereoselective Synthesis of syn- and cis-1,2-Diol Derivatives from Protected alpha-Hydroxy Ketones

    Czech Academy of Sciences Publication Activity Database

    Jahn, Emanuela; Smrček, Jakub; Pohl, Radek; Císařová, I.; Jones, P. G.; Jahn, Ullrich

    2015-01-01

    Roč. 2015, č. 35 (2015), s. 7785-7798. ISSN 1434-193X Grant ostatní: COST(XE) CM1201 Institutional support: RVO:61388963 Keywords : synthetic methods * reduction * diastereoselectivity * diols * ketones Subject RIV: CC - Organic Chemistry Impact factor: 3.065, year: 2014

  3. Enantioselective Synthesis of Vicinal (R,R)-Diols by Saccharomyces cerevisiae Butanediol Dehydrogenase.

    Science.gov (United States)

    Calam, Eduard; González-Roca, Eva; Fernández, M Rosario; Dequin, Sylvie; Parés, Xavier; Virgili, Albert; Biosca, Josep A

    2016-01-01

    Butanediol dehydrogenase (Bdh1p) from Saccharomyces cerevisiae belongs to the superfamily of the medium-chain dehydrogenases and reductases and converts reversibly R-acetoin and S-acetoin to (2R,3R)-2,3-butanediol and meso-2,3-butanediol, respectively. It is specific for NAD(H) as a coenzyme, and it is the main enzyme involved in the last metabolic step leading to (2R,3R)-2,3-butanediol in yeast. In this study, we have used the activity of Bdh1p in different forms-purified enzyme, yeast extracts, permeabilized yeast cells, and as a fusion protein (with yeast formate dehydrogenase, Fdh1p)-to transform several vicinal diketones to the corresponding diols. We have also developed a new variant of the delitto perfetto methodology to place BDH1 under the control of the GAL1 promoter, resulting in a yeast strain that overexpresses butanediol dehydrogenase and formate dehydrogenase activities in the presence of galactose and regenerates NADH in the presence of formate. While the use of purified Bdh1p allows the synthesis of enantiopure (2R,3R)-2,3-butanediol, (2R,3R)-2,3-pentanediol, (2R,3R)-2,3-hexanediol, and (3R,4R)-3,4-hexanediol, the use of the engineered strain (as an extract or as permeabilized cells) yields mixtures of the diols. The production of pure diol stereoisomers has also been achieved by means of a chimeric fusion protein combining Fdh1p and Bdh1p. Finally, we have determined the selectivity of Bdh1p toward the oxidation/reduction of the hydroxyl/ketone groups from (2R,3R)-2,3-pentanediol/2,3-pentanedione and (2R,3R)-2,3-hexanediol/2,3-hexanedione. In conclusion, Bdh1p is an enzyme with biotechnological interest that can be used to synthesize chiral building blocks. A scheme of the favored pathway with the corresponding intermediates is proposed for the Bdh1p reaction. PMID:26729717

  4. GC-MS/MS analysis of benzo(a)pyrene by ion trap tandem mass spectrometry

    International Nuclear Information System (INIS)

    The mass spectrometry using an ion trap tandem mass spectrometer has been investigated to find optimum conditions for the analysis of benzo(a)pyrene (3,4-benzpyrene). The applicability to a real soil sample was also investigated to verify the usefulness of the MS/MS (or collision induced dissociation, CID) analysis. The optimum CID condition was 1.5 and 0.45 for the RF excitation voltage and the q value, respectively. For comparison, CID and EI were applied to the analysis of a soil sample. CID analysis was more sensitive than EI analysis of the soil sample. The limit of detection (LOD) of benzo(a)pyrene was 3.18 ng mL-1 and 0.85 ng mL-1 for EI and MS/MS analysis, respectively. The precision at the soil sample for EI and CID showed relative standard deviations of 6.1% and 4.1%, respectively, and the concentrations were 168 μg kg-1 and 162 μg kg-1, respectively

  5. Studies on reactions of cerium(4) reduction with alcohols. Part 3. Reactions of cerium(4) reduction with butane-2,3-diol, butane-1,3-diol and cis-butene-2-diol-1,4 in aqueous solutions of perchloric acid

    International Nuclear Information System (INIS)

    The basic study of the red-ox reaction kinetics of cerium ions -diols-water systems in presence of the perchloric acid is given. Dependence of the various agents and its concentrations on equilibrium constants the complex formation reactions and complex stability are discussed and compared. (B.Cz.)

  6. Interaction of ferroceneboronic acid with diols at aqueous and non-aqueous conditions - signalling and binding abilities of an electrochemical probe for saccharides

    International Nuclear Information System (INIS)

    Highlights: • Electrochemical characterisation of ferroceneboronic acid-diol interactions in non-aqueous solutions. • Elucidation of the signalling process and signalling mechanism of the ferroceneboronic acid upon interaction with diols in aqueous and non-aqueous solutions. • Effect of coordination of boron atom on electrochemistry of ferroceneboronic acid in free and bound forms with diols. - Abstract: Ferroceneboronic acid (FcBA) was employed as a model compound for clarification of binding and signalling properties of molecular probe for saccharides. As the simplest electrochemically active boronic acid, its interactions with diverse diols were studied in homogeneous phase under aqueous and non-aqueous conditions. The FcBA-diol system was examined by cyclic voltammetry resulting in two redox pairs corresponding to free and bound forms of FcBA. Redox potential of the bound form of FcBA was shifted in the cathodic direction in aqueous conditions due to coordination of the hydroxyl group to the boron atom. Oppositely, the anodic shift of the redox potential was observed upon the interaction of FcBA with diols in non-aqueous solvents. The binding properties and signalling mechanism of electrochemically active boronic acids were deduced and the assumptions resulting from the electrochemical behaviour were confirmed by 1H and 11B NMR spectroscopies. The binding constants of the tested diols in aqueous and non-aqueous media were determined and compared

  7. Novel five- to ten-membered organoselenium heterocycles from the selenation of aromatic diols

    OpenAIRE

    Hua, Guoxiong; Fuller, Amy; Slawin, Alexandra M. Z.; Woollins, J. Derek

    2010-01-01

    This work is funded by the EPSRC UK Reaction of Woollins' reagent ― WR , 2,4-bis(phenyl)-1,3-diselenadiphosphetane 2,4-diselenide [{PhP(Se)(μ-Se)}2] ― with aromatic diols in refluxing toluene afforded a series of novel five- to ten-membered phosphorus-selenium heterocycles 1 – 10 with an O–P(Se)–O or O–P(Se)–Se–P(Se)–O or O–P(Se)–O–P(Se)–O linkage in 12–74 % isolated yields. It was found that the diphosphorus species O–P(Se)–Se–P(Se)–O rings could be readily reduced into the monophosphorus...

  8. Isolation and Crystal Structure of 1′,4′-Trans-diol of Abscisic Acid

    Institute of Scientific and Technical Information of China (English)

    WANG Tian-Shan; ZHOU Jin-Yan; TAN Hong

    2006-01-01

    1 ′,4′-Trans-diol of abscisic acid was isolated from botrytis cinerea as a colorless crystal. The molecular and crystal structures have been determined by X-ray diffraction analysis. It crystallizes in orthorhombic system, space group P212121 with a = 6.724(3), b = 17.559(6), c =12.265(2) (A), a = β = y = 90°, V = 1448.1(8) (A)3, Z = 4, Dx = 1.222 g/cm3, F(000) = 576 and μ(MoKa) = 0.087 mm-1. The final R = 0.0628 and wR = 0.1604 for 2501 independent reflections with Rint = 0.0160 and 1679 observed reflections with I >2σ(Ⅰ). There are three intermolecular hydrogen bonds in a unit cell.

  9. Bifunctional Nb/Ti-MCM-41 catalyst in oxidative acidic reaction of cyclohexene to diol

    International Nuclear Information System (INIS)

    Bifunctional oxidative and acidic catalyst was prepared by incorporating titanium ion (Ti4+) and niobic acid in meso porous molecular sieves MCM-41 structure. The catalyst is active both in oxidation, and acid-catalyzed reaction of olefin to diol. Nb/ Ti-MCM-41 catalyst was prepared by first synthesizing Ti-MCM-41 by hydrothermal method, followed by subsequent impregnation of niobic acid (Nb) into Ti-MCM-41 at various % wt Nb loading. The framework structure of Ti-MCM-41 collapsed after incorporation of Nb but the tetrahedral form of Ti4+ still maintained with octahedral Nb species. Both Bronsted and Lewis acid sites are present in all Nb/ Ti-MCM-41 samples. The formation of cyclohexanediol in the epoxidation of cyclohexene proved the bifunctional oxidative and acidic catalyst through the formation of cyclohexane oxide. The yield increased with the increase amount of the Bronsted acid sites provided by niobium species. (author)

  10. A NEW POLYMER-BOUND 1,2-DIOL AS A PROTECTING AGENT FOR SYMMETRICAL DIALDEHYDE

    Institute of Scientific and Technical Information of China (English)

    REN Qisheng; HUANG Wenqiang; ZHAO Fengzhi; Ho Binglin

    1989-01-01

    A novel polymer- bound 1,2 - diol, 3 - polystyrylsulfonyl- 1,2 - propanediol (6) had ben prepared by the reaction of sodium polystyrylsulfinate with allyl bromide, followed by oxidation and. hydrolysis or directly with 3 - chloro - 1,2 - propanediol in the presence of a phase transfer catalyst ,n - tetrabutylammonium iodide. The capacity of resin 6 for terephthaldehyde reached 1.43 mmol/g. The aldehydic groups attached to polymer 6 reacted with hydroxylamine hydrochloride or reduced by sodium borohydride giving p-formylbenzaldoxime (yield:89%)and p-formyl -benzalcohol (yield:73 A % ), respectively. The high yields of these polymer-supported reactions showed that the polymer 6 possessed the effective isolation of its reactive sites.

  11. Heterologous expression, purification, and properties of diol dehydratase, an adenosylcobalamin-dependent enzyme of Klebsiella oxytoca.

    Science.gov (United States)

    Tobimatsu, T; Sakai, T; Hashida, Y; Mizoguchi, N; Miyoshi, S; Toraya, T

    1997-11-01

    Recombinant adenosylcobalamin-dependent diol dehydratase of Klebsiella oxytoca overexpressed in Escherichia coli was purified to homogeneity. The enzyme has a low solubility and was extracted from the crude membrane fraction with 1% Brij 35 in a high recovery. Subsequent chromatography on DEAE-cellulose resulted in 4.9-fold purification of the enzyme in an overall yield of 65%. The enzyme thus obtained showed specific activity comparable to that of the wild-type enzyme of K. oxytoca. The apparent molecular weight determined by nondenaturing gel electrophoresis on a gradient gel was 220,000. The enzyme consists of equimolar amounts of the three subunits with apparent Mr of 60,000 (alpha), 30,000 (beta), and 19,000 (gamma). Therefore, the subunit structure of the enzyme is most likely alpha2beta2gamma2. The recombinant enzyme was also separated into components F and S upon DEAE-cellulose chromatography in the absence of substrate. Components F and S were identified as the beta subunit and alpha2gamma2 complex, respectively. Apparent Km for adenosylcobalamin, 1,2-propanediol, glycerol, and 1,2-ethanediol were 0.83 microM, 0.08 mM, 0.73 mM, and 0.56 mM, respectively. The three genes encoding the subunits of diol dehydratase were overexpressed individually or in various combinations in Escherichia coli. The alpha and gamma subunits mutually required each other for correct folding forming the soluble, active alpha2gamma2 complex (component S). Expression of the beta subunit in a soluble, active form (component F) was promoted by coexpression with both the alpha and gamma subunits, probably by coexistence with component S. These lines of evidence indicate that each subunit mutually affects the folding of the others in this heterooligomer enzyme. PMID:9344474

  12. The waterborne polyurethane dispersions based on polycarbonate diol: Effect of ionic content

    International Nuclear Information System (INIS)

    Three water-based polyurethane dispersions (PUD) were synthesized by modified dispersing procedure using polycarbonate diol (PCD), isophorone diisocyanate (IPDI), dimethylolpropionic acid (DMPA), triethylamine (TEA) and ethylenediamine (EDA). The ionic group content in the polyurethane-ionomer structure was varied by changing the amount of the internal emulsifier, DMPA (4.5, 7.5 and 10 wt.% to the prepolymer weight). The expected structures of obtained materials were confirmed by FTIR spectroscopy. The effect of the DMPA content on the thermal properties of polyurethane films was measured by TGA, DTA, DSC and DMTA methods. Increased DMPA amounts result in the higher hard segment contents and in the increase of the weight loss corresponding to the degradation of the hard segments. The reduction of hard segment content led to the elevated temperature of decomposition and to the decrease of the glass transition temperature and thermoplasticity. The atomic force microscopy (AFM), results indicated that phase separation between hard and soft segment of PUD with higher DMPA content is more significant than of PUD with lower DMPA content. The physico-mechanical properties, such as hardness, adhesion test and gloss of the dried films were also determined considering the effect of DMPA content on coating properties. Highlights: ► Polyurethane dispersions (PUD) were synthesized from polycarbonate diol. ► The effect of the DMPA content on the thermal properties of PUD films was measured. ► The thermal stability of PUD was increased by decreasing the DMPA content. ► Tg values of PUD were increased by increasing ionic content. ► The PUD with the highest content of DMPA showed more significant phase separation confirmed by AFM results

  13. Synthesis of a precursor for the preparation of 9 alpha,11 alpha-tritiated 5 alpha-androstane-3 alpha,17 beta-diol 17-glucuronide

    International Nuclear Information System (INIS)

    Starting from 11 beta-hydroxytestosterone, the synthesis of a strategic precursor, C-9 (11) unsaturated 5 alpha-androstane-3 alpha, 17 beta-diol 17-glucuronide (9a), for the preparation of 9 alpha,11 alpha-tritiated 5 alpha-androstane-3 alpha, 17 beta-diol 17-glucuronide has been achieved. The authors optimized the reaction conditions for catalytic reduction employing hydrogen and subsequent base hydrolysis followed by purification on Amberlite XAD-2 resin to obtain the saturated 5 alpha-androstane-3 alpha, 17 beta-diol 17-glucuronide

  14. MUTAGENICITY OF BENZO(A)PYRENE METABOLITES GENERATED ON THE ISOLATED PERFUSED LUNG FOLLOWING PARTICULATE EXPOSURE (JOURNAL VERSION)

    Science.gov (United States)

    The isolated perfused rabbit lung (IPL) is being used to study the effects of particulate exposure on the pulmonary metabolism of benzo(a)pyrene (BaP). Pasturealla-free New Zealand white rabbits were treated intraperitoneally with BaP prior to kill. The isolated lungs were then a...

  15. Benzo[a]pyrene co-metabolism in the presence of plant root extracts and exudates: Implications for phytoremediation

    International Nuclear Information System (INIS)

    Benzo[a]pyrene, a high molecular weight (HMW) polycyclic aromatic hydrocarbon (PAH) was removed from solution by Sphingomonas yanoikuyae JAR02 while growing on root products as a primary carbon and energy source. Plant root extracts of osage orange (Maclura pomifera), hybrid willow (Salix albaxmatsudana), or kou (Cordia subcordata), or plant root exudates of white mulberry (Morus alba) supported 15-20% benzo[a]pyrene removal over 24 h that was similar to a succinate grown culture and an unfed acetonitrile control. No differences were observed between the different root products tested. Mineralization of 14C-7-benzo[a]pyrene by S. yanoikuyae JAR02 yielded 0.2 to 0.3% 14CO2 when grown with plant root products. Collectively, these observations were consistent with field observations of enhanced phytoremediation of HMW PAH and corroborated the hypothesis that co-metabolism may be a plant/microbe interaction important to rhizoremediation. However, degradation and mineralization was much less for root product-exposed cultures than salicylate-induced cultures, and suggested the rhizosphere may not be an optimal environment for HMW PAH degradation by Sphingomonas yanoikuyae JAR02. - Bacterial benzo[a]pyrene cometabolism, a plant-microbe interaction affecting polycyclic aromatic hydrocarbon phytoremediation was demonstrated with Sphingomonas yanoikuyae JAR02 that utilized plant root extracts and exudates as primary substrates

  16. Effects of Benzo[a]pyrene on DNA Damage and Histological alterations in Gonad of Scallop Chlamys farreri

    OpenAIRE

    Jing-Jing, Miao; Lu-Qing, Pan; Jing, Liu; Lin, Zhang

    2008-01-01

    Effects of Benzo[a]pyrene on DNA Damage and Histological alterations in Gonad of Scallop Chlamys farreri correspondence: Corresponding author. (Lu-qing, Pan) (Lu-qing, Pan) The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China - No. 5--> , Yushan Road--> , Qingdao--> - CHINA (Jing-jing, Miao) The Key Laboratory of Mariculture, Ministry of Education, Ocean University ...

  17. METABOLISM AND DNA (DEOXYRIBONUCLEIC ACID) BINDING OF BENZO(A)PYRENE IN CULTURED HUMAN BLADDER AND BRONCHUS

    Science.gov (United States)

    The metabolism of benzo(a)pyrene (BP) was examined in ex-plant cultures of human bladder and bronchus. Three-day cultures were exposed to radiolabeled BP for 24 h, and the metabolism was determined by analysis of the level of binding of reactive metabolites to DNA, and by the rel...

  18. The separation and synthesis of lipidic 1,2- and 1,3-diols from natural phenolic lipids for the complexation and recovery of boron.

    Science.gov (United States)

    Tyman, John H P; Mehet, Satinderjit K

    2003-12-01

    A study has been made of the semi-synthesis of 1,3-diols (anacardic alcohols) from natural phenolic lipid resources from Anacardium occidentale and Anacardium giganteum which have given C15 and C11 derivatives, respectively. An isomeric 1,3-diol (isoanacardic alcohol) has been obtained from cardanol separated from technical cashew nut-shell liquid. Homologous 1,3-diols have been synthesised from a range of synthetic 2-alkyl-, 3-alkyl- and 4-alkylphenols and from 6-alkylsalicylic acids. The natural 1,2-diol, urushiol, from Rhus vernicifera has been purified. All these lipidic compounds have been studied for their complexation and the potential recovery of boron as boric acid. PMID:14623453

  19. Long chain diol index (LDI) as an organic-based sea surface temperature proxy in the Korean East Sea (NW Pacific)

    Science.gov (United States)

    Gal, Jong-Ku; Kim, Jung-Hyun; Kang, Su-Jin; Lee, Dong-Hun; Shin, Kyung-Hoon

    2016-04-01

    Long chain diol index (LDI) was introduced as an organic-based sea surface temperature (SST) proxy. LDI is expressed as the C30 1,15-diol abundance relative to those of C28 1,13-, C30 1,13- and C30 1,15-diols. There were a few studies which accessed the potential of LDI based on the culture, core top sediments, suspended particulate organic matters, and down-core sediments. However it is still unknown about the source of the diols and robustness as the SST proxy in the various marine environments. In the current study, we examined the applicability of the LDI in the East Sea of Korea where productivity and thus sedimentation rates are high. We will compare the LDI data with those of alkenone-based UK'37 by analyzing two multicores covering the last 100 year.

  20. Preferential Glutathione Conjugation of a Reverse Diol Epoxide Compared to a Bay Region Diol Epoxide of Phenanthrene in Human Hepatocytes: Relevance to Molecular Epidemiology Studies of Glutathione-S-Transferase Polymorphisms and Cancer

    OpenAIRE

    Hecht, Stephen S.; Berg, Jeannette Zinggeler; Hochalter, J. Bradley

    2009-01-01

    Bay region diol epoxides are recognized ultimate carcinogens of polycyclic aromatic hydrocarbons (PAH), and in vitro studies have demonstrated that they can be detoxified by conjugation with glutathione, leading to the widely investigated hypothesis that individuals with low activity forms of glutathione-S-transferases are at higher risk of PAH induced cancer, a hypothesis that has found at most weak support in molecular epidemiology studies. A weakness in this hypothesis was that the mercapt...

  1. Asbestos-catalyzed oxidation of benzo(a)pyrene by superoxide-peroxidized microsomes

    International Nuclear Information System (INIS)

    Asbestos and benzo(a)pyrene [B(a)P] are ubiquitous in our environment and both are recognized as causal factors for cancer in man and animals. In vitro studies showed a synergism in morphological transformation of mammalian cells treated with asbestos and B(a)P. It has been shown that asbestos can mediate lipid peroxidation and that iron cations might be involved in the catalytic activity of asbestos fibers. A previous study of B(a)P metabolism by microsomes showed that peroxidative conditions change the balance between activation and deactivation of B(a)P and demonstrated that catalytically active iron can play a role in this process. The present investigation examines the effect of asbestos on oxidation of B(a)P by superoxide - peroxidized microsomes in vitro

  2. Liquid chromatographic determination of benzo(a)pyrene in total particulate matter of cigarette smoke

    Energy Technology Data Exchange (ETDEWEB)

    Tomkins, B.A.; Jenkins, R.A.; Griest, W.H.; Reagan, R.R.; Holladay, S.K.

    1985-09-01

    The benzo(a)pyrene (BaP) delivery of reference and commercially available tobacco cigarettes, as well as reference and placebo marijuana cigarettes, is determined using a sequential liquid chromatographic/liquid chromatographic procedure. The total particulate matter of sample cigarette smoke is collected using a Cambridge filter pad, which is ultrasonically extracted with acetone. The resulting extract is filtered, then fractionated using semipreparative-scale normal phase liquid chromatography (LC). Quantitative determination is achieved using analytical-scale reverse phase LC equipped with a fluorescence detector. The method is precise (+/- 10-15% relative standard deviation) and yields 85% or better BaP recovery at the ng/cig. level. A single pad may be analyzed in 8 person-hours, while a more typical lot of 12 pads (6 pads each for 2 cigarette brands) may be analyzed in 10 person-days.

  3. Chlorophyll catalyse the photo-transformation of carcinogenic benzo[a]pyrene in water

    Science.gov (United States)

    Luo, Lijuan; Lai, Xueying; Chen, Baowei; Lin, Li; Fang, Ling; Tam, Nora F. Y.; Luan, Tiangang

    2015-08-01

    Algal blooms cause great damage to water quality and aquaculture. However, this study showed that dead algal cells and chlorophyll could accelerate the photo-transformation of benzo[a]pyrene (BaP), a ubiquitous and persistent pollutant with potently mutagenic and carcinogenic toxicities, under visible light irradiation. Chlorophyll was found to be the major active substance in dead algal cells, and generated a high level of singlet oxygen to catalyse the photo-transformation of BaP. According to various BaP metabolites formed, the degradation mechanism was proposed as that chlorophyll in dead algal cells photo-oxidized BaP to quinones via photocatalytic generation of singlet oxygen. The results provided a good insight into the role of chlorophyll in the photo-transformation of organic contaminants and could be a possible remediation strategy of organic pollutants in natural environment.

  4. Ring Expansion of Cyclic 1,2-Diols to form Medium Sized Rings via Ruthenium Catalyzed Transfer Hydrogenative [4+2] Cycloaddition

    OpenAIRE

    Kasun, Zachary A.; Geary, Laina M.; Krische, Michael J.

    2014-01-01

    A new method for the ring expansion of cyclic diols is described. Using improved conditions for the ruthenium(0) catalyzed cycloaddition of cyclic 1,2-diols with 1,3-dienes, fused [n.4.0] bicycles 3a–3r (n = 3–6) are formed, which upon exposure to iodosobenzene diacetate engage in oxidative cleavage to form the 9–12 membered rings 4a–4r.

  5. Sustainable Pathways to Pyrroles through Iron-Catalyzed N-Heterocyclization from Unsaturated Diols and Primary Amines.

    Science.gov (United States)

    Yan, Tao; Barta, Katalin

    2016-09-01

    Pyrroles are prominent scaffolds in pharmaceutically active compounds and play an important role in medicinal chemistry. Therefore, the development of new, atom-economic, and sustainable catalytic strategies to obtain these moieties is highly desired. Direct catalytic pathways that utilize readily available alcohol substrates have been recently established; however, these approaches rely on the use of noble metals such as ruthenium or iridium. Here, we report on the direct synthesis of pyrroles using a catalyst based on the earth-abundant and inexpensive iron. The method uses 2-butyne-1,4-diol or 2-butene-1,4-diol that can be directly coupled with anilines, benzyl amines, and aliphatic amines to obtain a variety of N-substituted pyrroles in moderate-to-excellent isolated yields. PMID:27493031

  6. [Diol column as stationary phase for high performance liquid chromatographic analysis of carbohydrates in drinks with evaporative light scattering detection].

    Science.gov (United States)

    Wei, Y; Guo, L; Ding, M Y

    2001-11-01

    A high performance liquid chromatographic method with a diol column and evaporative light scattering detector (ELSD) was established for the direct analysis of fructose, glucose, sucrose, maltose and raffinose in mixture. A separation column (Lichrospher 100 Diol, 250 mm x 4.0 mm i.d., 5 microns, Hewlett-Packard, USA) and a guard column (Zorbax Rx-SIL, 12.5 mm x 4.6 mm i.d., 5 microns) were used. The mobile phase was a mixture of dichloromethane-methanol (3.2:1, volume ratio). Regression equations revealed linear relationship (correlation coefficients: 0.995-0.999) between the mass of carbohydrates injected and the peak area of carbohydrates detected by ELSD. The detection limits of ELSD (S/N = 3) were about 0.20 microgram for all carbohydrates. This system could be used for the routine analysis of simple carbohydrates in some common drinks on market. PMID:12545463

  7. Synthesis of bio-based thermoplastic polyurethane elastomers containing isosorbide and polycarbonate diol and their biocompatible properties.

    OpenAIRE

    Oh, S. Y.; Kang, M. S.; Knowles, J. C.; Gong, M. S.

    2015-01-01

    A new family of highly elastic polyurethanes (PUs) partially based on renewable isosorbide were prepared by reacting hexamethylene diisocyanate with a various ratios of isosorbide and polycarbonate diol 2000 (PCD) via a one-step bulk condensation polymerization without catalyst. The influence of the isorsorbide/PCD ratio on the properties of the PU was evaluated. The successful synthesis of the PUs was confirmed by Fourier transform-infrared spectroscopy and (1)H nuclear magnetic resonance. T...

  8. Effect of various chemicals on the metabolism of benzo(a)pyrene by cultured rat colon

    DEFF Research Database (Denmark)

    1977-01-01

    hydroxylase (AHH) activity and binding levels of BP to macromolecules were higher in the descending colon when compared to other segments. The major metabolites of BP, extractable with ethylacetate, were quinones, tetrols, 7,8-diol and a peak containing 9,10-dihydroxy-9,10-dihydrobenzo(a)pyrene and 7......,8,9-trihydroxy-7,8-dihydrobenzo(a)pyrene. The binding levels of BP to DNA and protein in the explant was lowered by co-incubation with 7,8-benzoflavone (7,8-BF) (3.6 and 18.0 micron), a known inhibitor of AHH, and with disulfiram (100 micron), an anti-oxidant. The absence of vitamin A in the media also resulted...

  9. Juvenile hormone diol kinase, a calcium-binding protein with kinase activity, from the silkworm, Bombyx mori.

    Science.gov (United States)

    Li, Sheng; Zhang, Qi-Rui; Xu, Wei-Hua; Schooley, David A

    2005-11-01

    Juvenile hormone (JH) diol kinase (JHDK) is an important enzyme involved in the JH degradation pathway. Bombyx mori (Bommo)-JHDK cDNA (637bp) contains an open reading frame encoding a 183-amino acid protein, which reveals a high degree of identity to the two previously reported JHDKs. JHDK is similar to GTP-binding proteins with three conserved sequence elements involved in purine nucleotide binding, contains eight alpha-helices and three EF-hand motifs, and resembles the three-dimensional model of 2SCP and some other calcium-binding proteins. The Bommo-JHDK gene has only a single copy in the silkworm haploid genome, contains only one exon, and its 5'-upstream sequence does not have a JH response element. Although Bommo-JHDK is highly expressed in the gut of the silkworm, its mRNA expression remains at a constant level during larval development suggesting this enzyme is constitutive and not regulated by JH, at least at the transcriptional level. Recombinant Bommo-JHDK catalyzed the conversion of 10S-JH diol into JH diol phosphate, confirming its enzymatic function. Recombinant enzyme formed a dimer and had biochemical characteristics similar to other JHDKs. Bommo-JHDK, a calcium-binding protein with kinase activity, provides unique insights on how JH levels are regulated in the silkworm. PMID:16203205

  10. Antioxidants Inhibit Formation of 3-Monochloropropane-1,2-diol Esters in Model Reactions.

    Science.gov (United States)

    Li, Chang; Jia, Hanbing; Shen, Mingyue; Wang, Yuting; Nie, Shaoping; Chen, Yi; Zhou, Yongqiang; Wang, Yuanxing; Xie, Mingyong

    2015-11-11

    The capacities of six antioxidants to inhibit the formation of 3-monochloropropane-1,2 diol (3-MCPD) esters were examined in this study. Inhibitory capacities of the antioxidants were investigated both in chemical models containing the precursors (tripalmitoyl glycerol, 1,2-dipalmitoyl-sn-glycerol, monopalmitoyl glycerol, and sodium chloride) of 3-MCPD esters and in oil models (rapeseed oil and sodium chloride). Six antioxidants, butylated hydroxytoluene (BHT), butylated hydroxy anisole (BHA), tert-butyl hydroquinone (TBHQ), propyl gallate (PG), L-ascorbyl palmitate (AP), and α-tocopherol (VE), were found to exhibit inhibiting capacities on 3-MCPD ester formation both in chemical models and in oil models. TBHQ provided the highest inhibitory capacity both in chemical models and in oil models; 44% of 3-MCPD ester formation was inhibited in the presence of TBHQ (66 mg/kg of oil) after heating of rapeseed oil at 230 °C for 30 min, followed by PG and AP. BHT, BHA, and VE appeared to have weaker inhibitory abilities in both models. VE exhibited the lowest inhibition rate; 22% of 3-MCPD esters were inhibited in the presence of VE (172 mg/kg of oil) after heating of rapeseed oil at 230 °C for 30 min. In addition, the inhibition rates of PG and VE decreased dramatically with an increase in temperature or heating time. The results suggested that some antioxidants, such as TBHQ, PG, and AP, could be the potential inhibitors of 3-MCPD esters in practice. PMID:26478126

  11. Binding site for the adenosyl group of coenzyme B12 in diol dehydrase

    International Nuclear Information System (INIS)

    The binding of cob(II)alamin (CblII) and 5'-deoxyadenosine to diol dehydrase was studied spectroscopically and with [U-14C]5'-deoxyadenosine. CblII was bound to this enzyme forming a tight 1:1 complex which was resistant to oxidation by O2 even in the presence of CN-. An irreversible 1:1:1 ternary complex was formed between enzyme, CblII, and 5'-deoxyadenosine, when the enzyme was incubated first with the nucleoside and then with CblII. When this order of addition of the constituents was reversed, no 5'-deoxyadenosine was bound to the enzyme-CblII complex. Hydroxocobalamin could also bind to the enzyme together with the nucleoside, while other cob(III)alamins bearing a bulkier Co beta ligand displaced the nucleoside upon binding to the enzyme. The binding of [U-14C]5'-deoxyadenosine was strongly inhibited by unlabeled 5'-deoxy-ara-adenosine, 4',5'-anhydroadenosine, adenosine, adenine, and 5',8-cyclic adenosine, in this order, but not by 5'-deoxyuridine. These results constitute direct evidence for the presence of the binding site for the adenosyl group of adenosylcobalamin, which is spatially limited to and highly specific for adenine nucleosides. The binding of 5'-deoxyadenosine to the apoenzyme was reversible

  12. Urinary 5α-androstane-3α,17β-diol radioimmunoassay: a new clinical evaluation

    International Nuclear Information System (INIS)

    A rapid specific and reliable RIA for urinary 5α-androstane-3α, 17β-diol (Adiol) is described using chromatographical purification and a specific antibody. Values are reported under some physiological and pathological conditions in 179 individuals. In 43 normal adult men the mean (+- SD) urinary Adiol excretion was 193 +- 77 μg/24 h, and in 29 normal women it was 44 +- 23 μg/24 h. These values are significantly different (P < 0.01). In 49 hirsute women, urinary Adiol Excretion was elevated (137 +- 51 μg/24 h) and significantly different from this value in normal women (P < 0.01). The urinary Adiol excretion in 10 postmenopausal women was very low (< 5 μg/24 h). In normal adult subjects, the theoretical contribution to urinary Adiol of the major secreted androgens was calculated. Whereas dehydroisoandrosterone and dehydroisoandrosterone sulfate yield the same amount of urinary Adiol in both sexes, testosterone is the main precursor of Adiol in men and androstenedione is the main precursor in normal premenopausal and hirsute women. However, the amount of Adiol recovered in the 24-h urine depends not only on the secretion rate of androstenedione and testosterone but is also related to the testosterone 5α-reductase activity present in androgen target cells, especially in sexual skin

  13. Mussel-inspired soft-tissue adhesive based on poly(diol citrate) with catechol functionality.

    Science.gov (United States)

    Ji, Yali; Ji, Ting; Liang, Kai; Zhu, Lei

    2016-02-01

    Marine mussels tightly adhering to various underwater surfaces inspires human to design adhesives for wet tissue adhesion in surgeries. Characterization of mussel adhesive plaques describes a matrix of proteins containing 3,4-dihydroxyphenylalanine (DOPA), which provides strong adhesion in aquatic conditions. Several synthetic polymer systems have been developed based on this DOPA chemistry. Herein, a citrate-based tissue adhesives (POEC-d) was prepared by a facile one-pot melt polycondensation of two diols including 1,8-octanediol and poly(ethylene oxide) (PEO), citric acid (CA) and dopamine, and the effects of hydrophilic and soft PEO on the properties of adhesives were studied. It was found that the obtained adhesives exhibited water-soluble when the mole ratio of PEO to 1,8-octanediol was 70%, and the equilibrium swelling percentage of cured adhesive was about 144%, and degradation rate was in the range of 1-2 weeks. The cured adhesives demonstrated soft rubber-like behavior. The lap shear adhesion strength measured by bonding wet pig skin was in the range of 21.7-33.7 kPa, which was higher than that of commercial fibrin glue (9-15 kPa). The cytotoxicity tests showed the POEC-d adhesives had a low cytotoxicity. Our results supports that POEC-d adhesives, which combined strong wet adhesion with good biodegradability, acceptable swelling ratio, good elasticity and low cytotoxicity, have potentials in surgeries where surgical tissue adhesives, sealants, and hemostatic agents are used. PMID:26704547

  14. Investigation on the Protective Effects of Cranberry Against the DNA Damage Induced by Benzo[a]pyrene

    OpenAIRE

    Morales-González, José A.; Jaime Esquivel-Soto; César Esquivel-Chirino; Teresa Sumaya-Martínez; Tomas Fregoso-Aguilar; Jorge Mendoza-Pérez; José Gutiérrez-Salinas; Manuel Sánchez-Gutiérrez; Clara Zúñiga Pérez; Jeannett A. Izquierdo-Vega; Gloria Solano-Solano; Carmen Valadez-Vega; Sonia Fragoso-Antonio; Eduardo Madrigal-Santillán

    2012-01-01

    There are few reports that demonstrate the antigenotoxic potential of cranberries. Although the types of berry fruits consumed worldwide are many, this paper focuses on cranberries that are commonly consumed in Mexico (Vaccinium macrocarpon species). The purpose of the present study is to determine whether cranberry ethanolic extract (CEE) can prevent the DNA damage produced by benzo[a]pyrene (B[a]P) using an in vivo mouse peripheral blood micronucleus assay. The experimental groups were orga...

  15. Seasonal trends of benzo(a)pyrene in suspended particulate matter in urban areas of Belgrade, Serbia

    OpenAIRE

    Snežana Matić-Besarabić; Ljiljana Adjanski-Spasić; Milena Jovašević-Stojanović; Anka Cvetković; Dragan A. Marković

    2010-01-01

    Polycyclic aromatic hydrocarbons (PAHs) were identified to be one of the major toxic air pollutants in urban environment. PAHs are mostly formed during incomplete combustion or pyrolysis of organic material. According to Serbian National Legislation, benzo(a)pyrene (BaP) concentration in total suspended particles (TSP) in ambient air in the Belgrade metropolitan area has been determined in the last ten years, as a part of a local air pollution monitoring program performed by the Public Health...

  16. Intercalation of 1,n-diols into strontium phenylphosphonate: how the shape of the host layers influences arrangement of the guest molecules.

    Science.gov (United States)

    Melánová, Klára; Kovář, Petr; Beneš, Ludvík; Svoboda, Jan; Veteška, Marek; Pospíšil, Miroslav; Zima, Vítězslav

    2015-12-15

    Strontium phenylphosphonate intercalates with 1,n diols (n=2-4, 6-8) having general formula SrC6H5PO3⋅x(HO(CH2)nOH)⋅yH2O were prepared by precipitation from strontium phenylphosphonate solution and the corresponding diols. Prepared compounds exhibit a very good stability at ambient conditions. The intercalates were characterized by X-ray diffraction, thermogravimetry and elemental analysis. Thanks to the existence of free spaces among the benzene rings the diols exhibit a peculiar intercalation behavior. This behavior is explained on the basis of molecular simulation, which facilitated to elucidate the arrangement of the diol (guest) molecules in the specifically shaped space between the layers of the host material. From the structural point of view the intercalates can be divided into two subgroups: (i) intercalates with 1,2- to 1,4-diols and (ii) intercalates with 1,6- to 1,8-diols. The alkanediols of the first group are immersed in the free spaces among the benzene groups, their molecules adopt a horseshoe shape meaning cis conformation and are bonded by both of their OH groups to one host layer. The longer alkanediol chains of the second group allow anchoring to both neighboring layers of the host forming a kind of pillared structure in the interlayer space. The diol molecules are in this case bonded to the host layers by their OH groups to the oxygen atoms of the host layers and to water molecules present in the interlayer space through hydrogen bonds. The values of the basal spacing obtained from the experimental powder X-ray patterns are in a very good agreement with the basal spacing values calculated from the models. The molecular simulation of a 1,5-pentanediol intercalate, which we were not be able to synthesize, explained why this intercalate cannot be stable. PMID:26319335

  17. Abscisic (ABA)-aldehyde is a precursor to, and 1',4'-trans-ABA-diol a catabolite of, ABA in apple

    International Nuclear Information System (INIS)

    Previous 18O labeling studies of abscisic acid (ABA) have shown that apple (Malus domestica Borkh. cv Granny Smith) fruits synthesize a majority of [18O]ABA with the label incorporated in the 1'-hydroxyl position and unlabeled in the carboxyl group (JAD Zeevaart, TG Heath, DA Gage [1989] Plant Physiol 91: 1594-1601). It was proposed that exchange of 18O in the side chain with the medium occurred at an aldehyde intermediate stage of ABA biosynthesis. We have isolated ABA-aldehyde and 1'-4'-trans-ABA-diol (ABA-trans-diol) from 18O-labeled apple fruit tissue and measured the extent and position of 18O incorporation by tandem mass spectrometry. 18O-Labeling patterns of ABA-aldehyde, ABA-trans-diol, and ABA indicate that ABA-aldehyde is a precursor to, and ABA-trans-diol a catabolite of, ABA. Exchange of 18O in the carbonyl of ABA-aldehyde can be the cause of loss of 18O from the side chain of [18O]ABA. Results of feeding experiments with deuterated substrates provide further support for the precursor-product relationship of ABA-aldehyde → ABA → ABA-trans-diol. The ABA-aldehyde and ABA-trans-diol contents of fruits and leaves were low, approximately 1 and 0.02 nanograms per gram fresh weight for ABA-aldehyde and ABA-trans-diol, respectively, while ABA levels in fruits ranged from 10 to 200 nanograms per gram fresh weight. ABA biosynthesis was about 10-fold lower in fruits than in leaves. In fruits, the majority of ABA was conjugated to β-D-glucopyranosyl abscisate, whereas in leaves ABA was mainly hydroxylated to phaseic acid. Parallel pathways for ABA and trans-ABA biosynthesis and conjugation in fruits and leaves are proposed

  18. Determination of benzo[a]pyrene and dibenzopyrenes in a Chinese coal fly ash certified reference material.

    Science.gov (United States)

    Masala, Silvia; Bergvall, Christoffer; Westerholm, Roger

    2012-08-15

    Air pollution from coal combustion is of great concern in China because coal is the country's principal source of energy and it has been estimated that coal combustion is one of the main sources of polycyclic aromatic hydrocarbon (PAH) emissions in the nation. This study reports the concentrations of 15 PAHs including benzo[a]pyrene, dibenzo[a,l]pyrene, dibenzo[a,e]pyrene, dibenzo[a,i]pyrene and dibenzo[a,h]pyrene in a coal fly ash certified reference material (CRM) from China. To the best of our knowledge, dibenzo[a,l]pyrene, dibenzo[a,i]pyrene and dibenzo[a,h]pyrene concentrations in coal fly ash particles have not previously been reported. Benzo[a]pyrene is the only one of the studied hydrocarbons whose concentration in the coal fly ash CRM had previously been certified. The concentration of this species measured in this present work was twice the certified value. This is probably because of the exhaustive accelerated solvent extraction method employed. Consecutive extractions indicated an extraction recovery in excess of 95% for benzo[a]pyrene. For the other determined PAHs, repeat extractions indicated recoveries above 90%. PMID:22728296

  19. Benzo[a]pyrene and Benzo[k]fluoranthene in some processed fish and fish products.

    Science.gov (United States)

    Olatunji, Olatunde S; Fatoki, Olalekan S; Opeolu, Beatrice O; Ximba, Bhekumusa J

    2015-01-01

    In this study, the concentration levels of the probable carcinogenic PAH fractions, benzo[a]pyrene (BaP) and benzo[k]fluoranthrene (BkF) in fillets of some processed fish species were investigated. Fish species comprising Merluccius poli (hake), Tyrsites atun (snoek), Seriola lalandi (yellow-tail) and Brama brama (angel fish) were bought in fish shops at Gordon's Bay, Western Cape, South Africa. The fish were gutted, filleted and prepared for edibility by frying, grilling and boiling. Polycyclic aromatic hydrocarbons were extracted from each homogenized fish sample, cleaned-up using solid phase extraction (SPE), and analysed for the PAH fractions, BaP and BkF using a Gas Chromatograph coupled with a Flame Ionization Detector (GC-FID). The sum of the two PAHs (∑2PAH) i.e., BaP and BkF ranged between 0.56 and 1.46 µg/kg, in all boiled, grilled and fried fish species. The fried fish extracts showed significantly higher (p < 0.05) abundance of ∑2PAH, than grilled and boiled fish. Dietary safety and PAHs toxicity was also discussed. PMID:25607603

  20. Benzo[a]pyrene and Benzo[k]fluoranthene in Some Processed Fish and Fish Products

    Directory of Open Access Journals (Sweden)

    Olatunde S. Olatunji

    2015-01-01

    Full Text Available In this study, the concentration levels of the probable carcinogenic PAH fractions, benzo[a]pyrene (BaP and benzo[k]fluoranthrene (BkF in fillets of some processed fish species were investigated. Fish species comprising Merluccius poli (hake, Tyrsites atun (snoek, Seriola lalandi (yellow-tail and Brama brama (angel fish were bought in fish shops at Gordon’s Bay, Western Cape, South Africa. The fish were gutted, filleted and prepared for edibility by frying, grilling and boiling. Polycyclic aromatic hydrocarbons were extracted from each homogenized fish sample, cleaned-up using solid phase extraction (SPE, and analysed for the PAH fractions, BaP and BkF using a Gas Chromatograph coupled with a Flame Ionization Detector (GC-FID. The sum of the two PAHs (∑2PAH i.e., BaP and BkF ranged between 0.56 and 1.46 µg/kg, in all boiled, grilled and fried fish species. The fried fish extracts showed significantly higher (p < 0.05 abundance of ∑2PAH, than grilled and boiled fish. Dietary safety and PAHs toxicity was also discussed.

  1. Effects of benzo(a)pyrene exposure on the antioxidant enzyme activity of scallop Chlamys farreri

    Institute of Scientific and Technical Information of China (English)

    PAN Luqing; REN Jiayun; ZHENG Debin

    2009-01-01

    Scallop Chlamys farreri was exposed to different concentrations of benzo(a)pyrene (BaP) (0.5 μg/L, 1.0 μg/L, 10.0 μg/L and 50.0 μg/L) for 30 days in seawater. The 7-ethoxyresorufin O-deethylase (EROD) activity was significantly induced, and increased with the increasing BaP concentration. The glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), Glutathione peroxidase (GPx) activities increased in short time at low concentration of BaP, and was significantly depressed at high concentrations. Scallop gill was more sensitive to BaP than the digestive gland, and the digestive gland was the main tissue to deal with oxyradicals. The contents of malondialdehyde (MDA) increased with the exposure time and there was a positive correlation (concentration-effect) between the MDA content and the concentration of BaP. The biomarkers determined in this experiment had important roles in detoxification, and showed great potential as biomarkers for oxidative stress. Controlled laboratory experiments designed to simulate field exposure scenarios are particularly useful in ascertaining biomarkers suitable for use with complex contaminant mixtures in the marine environment.

  2. Skin tumor-initiating activities of the twelve isomeric phenols of benzo(a)pyrene

    International Nuclear Information System (INIS)

    The skin tumor-initiating activities of the 12 isomeric phenols of benzo(a)pyrene (BP) were determined in mice by use of a two-stage system of tumorigenesis. 11-Hydroxybenzo(a)pyrene was moderately active, whereas 2-hydroxybenzo(a)pyrene and BP were strong tumor initiators when applied topically to CD-1 mice and followed by twice-weekly applications of the promoter 12-O-tetradecanoylphorbol-13-acetate. 1-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, and 12-hydroxybenzo(a)pyrene had less than 5% of the tumor-initiating activity of BP when the data were expressed as papillomas per mouse. After 30 weeks of promotion, the number of papillomas per mouse was 8.4, 8.5, and 2.8, respectively, for the animals treated with BP, 2-hydroxybenzo(a)pyrene, and 11-hydroxybenzo(a)pyrene. A 5-week latency period before the appearance of the first tumor was observed after the application of either 2-hydroxybenzo(a)pyrene or BP, whereas a slightly longer latency period of 7 weeks was observed following application of 11-hydroxybenzo(a)pyrene. The time required for 50% of the animals to develop tumors was 13 weeks for animals treated with BP and 15 weeks for animals treated with 2- or 11-hydroxybenzo(a)pyrene

  3. Seasonal trends of benzo(apyrene in suspended particulate matter in urban areas of Belgrade, Serbia

    Directory of Open Access Journals (Sweden)

    Snežana Matić-Besarabić

    2010-09-01

    Full Text Available Polycyclic aromatic hydrocarbons (PAHs were identified to be one of the major toxic air pollutants in urban environment. PAHs are mostly formed during incomplete combustion or pyrolysis of organic material. According to Serbian National Legislation, benzo(apyrene (BaP concentration in total suspended particles (TSP in ambient air in the Belgrade metropolitan area has been determined in the last ten years, as a part of a local air pollution monitoring program performed by the Public Health Institute of Belgrade and funded by Belgrade’s Municipality. Air samples for analysis of BaP in suspended particleshave been collected (as 24 h sample once per month at selected onitoring sites within the municipal air quality monitoring network. At the beginning, according to National Regulation, all samples were taken as total suspended particles (TSP. Since mid-2008, the procedure of sampling methodology was harmonized with EU requirements and solid fraction PM10 has been collected and analyzed using GC/MS. In this study, we have analyzed results of TSP collected between 2005 and 2008. Looking through the results obtained during the period of a whole year, it can be noticed that concentrations of BaP were much higher during winter season at almost all measuring sites.

  4. Can biomonitors effectively detect airborne benzo[a]pyrene? An evaluation approach using modelling

    Science.gov (United States)

    Ratola, Nuno; Jiménez-Guerrero, Pedro

    2016-04-01

    Biomonitoring data available on levels of atmospheric polycyclic aromatic hydrocarbons (PAHs) in pine needles from the Iberian Peninsula were used to estimate air concentrations of benzo[a]pyrene (BaP) and, at the same time, fuelled the comparison with chemistry transport model representations. Simulations with the modelling system WRF+EMEP+CHIMERE were validated against data from the European Monitoring and Evaluation Programme (EMEP) air sampling network. Modelled atmospheric concentrations were used as a consistent reference in order to compare the performance of vegetation-to-air estimating methods. A spatial and temporal resolution of 9 km and 1 h was implemented. The field-based database relied on a pine needles sampling scheme comprising 33 sites in Portugal and 37 sites in Spain complemented with the BaP measurements available from the EMEP sites. The ability of pine needles to act as biomonitoring markers for the atmospheric concentrations of BaP was estimated by converting the levels obtained in pine needles into air concentrations by six different approaches, one of them presenting realistic concentrations when compared to the modelled atmospheric values. The justification for this study is that the gaps still exist in the knowledge of the life cycles of semi-volatile organic compounds (SVOCs), particularly the partition processes between air and vegetation. The strategy followed in this work allows for the effective estimation by the model of concentrations in air and vegetation and of the best approaches to estimate atmospheric levels from values found in vegetation.

  5. Synthesis of modified potato starches for aqueous solubilization of benzo[a]pyrene.

    Science.gov (United States)

    Delsarte, Isabelle; Danjou, Pierre-Edouard; Veignie, Etienne; Rafin, Catherine

    2016-06-25

    For soil rehabilitation, the surfactant-enhanced remediation has emerged as a promising technology. For this purpose, starch derivatives were difunctionalized by 1,4-butane sultone (BS) and 2-octen-1-ylsuccinic anhydride (OSA). Eight distinct products were obtained under different synthesis conditions. The chemical structural characteristics were investigated by (1)H NMR spectroscopy. The compounds were evaluated for their apparent aqueous solubility and their ability to increase the solubility of a hydrophobic pollutant such as benzo[a]pyrene (BaP), used as a polycyclic aromatic hydrocarbon model. In comparison with native starch, the best obtained compound increased starch apparent aqueous solubility by a factor of 10 (up to 3.50g/L) and also stimulated 77-fold BaP aqueous solubilization (up to 232.97μg/L) underlining its very high surfactant property. In this study, the right balance between hydrophobic character (octenyl succinate group (OS) grafted) of starch derivatives and starch apparent aqueous solubility (BS grafted) was highlighted. PMID:27083796

  6. Repellent activities of stereoisomers of p-menthane-3,8-diols against Anopheles gambiae (Diptera: Culicidae).

    Science.gov (United States)

    Barasa, Stephen S; Ndiege, Isaiah O; Lwande, Wilber; Hassanali, Ahmed

    2002-09-01

    Four stereoisomers of p-menthane-3,8-diol, which make up the natural product obtained from Eucalyptus citriodora, were synthesized through stereoselective procedures. Repellency assays showed that all the four were equally active against Anopheles gambiae s.s. Racemic blends and the diastereoisomeric mixture of all the four isomers were also equally repellent. 1-alpha-terpeneol, with a single hydroxyl function at C-8 and unsaturation at C-8, and menthol, with a single hydroxyl function at C-3, were not repellent. The practical implication of these results is discussed. PMID:12349856

  7. (Enantio)selective Hydrogen Autotransfer: Ruthenium-Catalyzed Synthesis of Oxazolidin-2-ones from Urea and Diols.

    Science.gov (United States)

    Peña-López, Miguel; Neumann, Helfried; Beller, Matthias

    2016-06-27

    A novel strategy for the synthesis of oxazolidin-2-ones from vicinal diols and urea is described. In this heterocycle synthesis, two different C-O and C-N bonds are sequentially formed in a domino process consisting of nucleophilic substitution and alcohol amination. The use of readily available starting materials and the good atom economy render this process environmentally benign. While this transformation is already highly chemo- and regioselective, we also developed the first asymmetric version of this method using (R)-(+)-MeO-BIPHEP as the chiral ligand. PMID:27072612

  8. Improved straightforward chemical synthesis of dihydroxyacetone phosphate through enzymatic desymmetrization of 2,2-dimethoxypropane-1,3-diol.

    Science.gov (United States)

    Charmantray, Franck; El Blidi, Lahssen; Gefflaut, Thierry; Hecquet, Laurence; Bolte, Jean; Lemaire, Marielle

    2004-12-24

    Dihydroxyacetone phosphate (DHAP) was synthesized in high purity and yield in four steps starting from dihydroxyacetone dimer (DHA) (47% overall yield). DHA was converted into 2,2-dimethoxypropane-1,3-diol, which was desymmetrized by acetylation with lipase AK. The alcohol function was phosphorylated to give dibenzyl phosphate ester 4. From 4, two routes were investigated for large-scale synthesis of DHAP. First, acetate hydrolysis was performed prior to hydrogenolysis of the phosphate protective groups. The acetal hydrolysis was finally catalyzed by the phosphate group itself. Second, acetate and acetal hydrolysis were performed in one single step after hydrogenolysis. PMID:15609974

  9. New thermally stable polyesters based on 2,5-pyridinedicarbonyl dichloride and aromatic diols: Synthesis and characterization

    Institute of Scientific and Technical Information of China (English)

    Hossein Nasr Isfahani; Khalil Faghihi

    2009-01-01

    Six new thermally stable polyesters (4a-f) were synthesized through the solution polycondensation reaction of 2,5-pyridine dicarbonyldichloride (2) with six aromatic diols in N,N'-dimethyl acetamide (DMAc) solution and in the presence of pyridine as a base. The polycondensation reactions produce a series of new polyesters (4a-f) in high yields, and inherent viscosity between 0.30 and 0.55 dL/g. The resulting polyesters were characterized by elemental analysis, viscosity measurements, thermal gravimetric analysis (TGA and DTG), solubility test, Fourier transform infrared (FT-IR) spectroscopy and gel permeation chromatography (GPC).

  10. Conglomerate formative precursor of chiral drug timolol: 3-(4-Morpholino-1,2,5-thiadiazol-3-yloxy)-propane-1,2-diol

    Science.gov (United States)

    Bredikhin, Alexander A.; Zakharychev, Dmitry V.; Fayzullin, Robert R.; Bredikhina, Zemfira A.; Gubaidullin, Aidar T.

    2015-05-01

    Solid state properties of 3-(4-N-morpholino-1,2,5-thiadiazol-3-yloxy)-propane-1,2-diol 3, the synthetic precursor of popular drug timolol, have been investigated. The original solubility test, the data of X-ray diffraction and DSC methods indicate that the compound is prone to spontaneous resolution. Diol 3 crystallizing from both enantiopure or racemic feed material forms "guaifenesin-like" crystal packing in which the classic H-bonded bilayers, framed in both sides by hydrophobic molecular fragments, act as the basic supramolecular motif. The main chain conformation of the molecules in the crystals of diol 3 differs from that in the guaifenesin crystals, and this fact changes the absolute configuration of spiral columns formed by intermolecular hydrogen bonds in crystals of 3 as compared with guaifenesin crystals.

  11. The mixed-ligand ternary complexes of neodymium(III) with L-histidine and L-cysteine with various diols

    International Nuclear Information System (INIS)

    The stability constants of the ternary complexes of the type MAB, MA2B, MAB2 where M = Neodymium(III), A = amino acids and B = diols, have been investigated by pH-metric technique (μ = 0.2, KNO3 at 30 +- 1degC) with both amino acids used as primary ligand. Stability constant data indicates that MA2B species were more stable than MAB and MAB2. The diols are responsible for the change in stability. The stability constants were correlated with basicities of different ligands present in the complexes. (author)

  12. Stability and in vivo behavior of Rh[16aneS4-diol]211At complex: A potential precursor for astatine radiopharmaceuticals

    International Nuclear Information System (INIS)

    Introduction: The heavy halogen 211At is of great interest for targeted radiotherapy because it decays by the emission of short-range, high-energy α-particles. However, many astatine compounds that have been synthesized are unstable in vivo, providing motivation for seeking other 211At labeling strategies. One relatively unexplored approach is to utilize prosthetic groups based on astatinated rhodium (III) complex stabilized with a tetrathioether macrocyclic ligand – Rh[16aneS4-diol]211At. The purpose of the current study was to evaluate the in vitro and in vivo stability of this complex in comparison to its iodine analog – Rh[16aneS4-diol]131I. Methods: Rh[16aneS4-diol]211At and Rh[16aneS4-diol]131I complexes were synthesized and purified by HPLC. The stability of both complexes was evaluated in vitro by incubation in phosphate-buffered saline (PBS) and human serum at different temperatures. The in vivo behavior of the two radiohalogenated complexes was assessed by a paired-label biodistribution study in normal Balb/c mice. Results: Both complexes were synthesized in high yield and purity. Almost no degradation was observed for Rh[16aneS4-diol]131I in PBS over a 72 h incubation. The astatinated analog exhibited good stability in PBS over 14 h. A slow decline in the percentage of intact complex was observed for both tracers in human serum. In the biodistribution study, retention of 211At in most tissues was higher than that of 131I at all time points, especially in spleen and lungs. Renal clearance of Rh[16aneS4-diol]211At and Rh[16aneS4-diol]131I predominated, with 84.1 ± 2.3% and 94.6 ± 0.9% of injected dose excreted via the urine at 4 h. Conclusions: The Rh[16aneS4-diol]211At complex might be useful for constructing prosthetic groups for the astatination of biomolecules and further studies are planned to evaluate this possibility

  13. Organocatalyzed direct aldol condensation using L-proline and BINAM-prolinamides: regio-, diastereo-, and enantioselective controlled synthesis of 1,2-diols

    OpenAIRE

    Guillena Townley, Gabriela; Hita López, María del Carmen; Nájera Domingo, Carmen

    2006-01-01

    Recoverable BINAM-prolinamide derivatives, as well as L-proline, give results complementary to antibodies when used as organocatalysts for aldol eactions between aldehydes and α-alkoxyacetones driving regioselectively to anti/syn-1,2-diols. The formation of the iso-regioisomer is suppressed using α-hydroxyacetone in DMSO at rt, achieving the corresponding anti-1,2-diol with ee’s up to 85%. For α-alkoxyacetones (methoxy, benzyloxy, and tert-butyldimethylsilyloxy), the highest regio- and dia...

  14. Preparation and surface active properties of oxypropylated diol monoesters of fatty acids with an amide oxime terminal group

    Directory of Open Access Journals (Sweden)

    Eissa, A. M.F.

    1994-10-01

    Full Text Available Locally produced non-edible oil, namely, rice bran oil (R.B.O. was utilized as starting materials for preparing new nonionic surfactant. Oxypropylated diol monoesters of linoleic and rice bran oil fatty acids were prepared. Also amide oxime derivatives were obtained. Surface active properties of these compounds were measured. Under neutral condition amide eximes served as nonionic surfactants and their properties were similar to other oxypropylated monoesters.

    Se ha utilizado un aceite no comestible de producción local, denominado, aceite de salvado de arroz (R.B.O. como materia prima para la preparación de nuevos tensioactivos no iónicos. Se prepararon diol monoésteres oxipropilados de ácido linoleico y ácidos grasos de aceite de salvado de arroz. También se obtuvieron los derivados de amido oxima. Se midieron las propiedades de tensión superficial de estos compuestos. Bajo condiciones neutras las amido eximas sirvieron como tensioactivos no iónicos y sus propiedades fueron similares a los de otros monoésteres oxipropilados.

  15. Superparamagnetic Ironoxide Nanoparticles via Ligand Exchange Reactions: Organic 1,2-Diols as Versatile Building Blocks for Surface Engineering

    Directory of Open Access Journals (Sweden)

    Robert Sachsenhofer

    2008-09-01

    Full Text Available A method for the preparation of ligand-covered superparamagnetic iron oxide nanoparticles via exchange reactions is described. 1,2-diol-ligands are used to provide a stable binding of the terminally modified organic ligands onto the surface of γ-Fe2O3-nanoparticles (r∼4 nm. The 1,2-diol-ligands are equipped with variable terminal functional groups (i.e., hydrogen bonding moieties, azido- bromo-, fluorescent moieties and can be easily prepared via osmium tetroxide-catalyzed 1,2-dihydroxylation reactions of the corresponding terminal alkenes. Starting from octylamine-covered Î��-Fe2O3-nanoparticles, ligand exchange was effected at 50∘C over 24–48 hours, whereupon complete ligand exchange is taking place as proven by thermogravimetric (TGA- and IR-spectroscopic measurements. A detailed kinetic analysis of the ligand exchange reaction was performed via TGA analysis, demonstrating a complete ligand exchange after 24 hours. The method offers a simple approach for the generation of various γ-Fe2O3-nanoparticles with functional organic shells in a one-step procedure.

  16. Deep sequencing-based transcriptome profiling analysis of Chlamys farreri exposed to benzo[a]pyrene.

    Science.gov (United States)

    Cai, Yuefeng; Pan, Luqing; Hu, Fengxiao; Jin, Qian; Liu, Tong

    2014-11-10

    Whole-genome transcriptome measurements are pivotal for characterizing molecular mechanisms of chemicals and predicting toxic classes, such as genotoxicity and carcinogenicity, from in vitro and in vivo assays. We analyzed the dynamic defense transcriptome responsive to Chlamys farreri upon exposure to benzo[a]pyrene (BaP) using a digital gene expression (DGE) approach. Following exposure, 251 and 177 genes were up-regulated, and 142 and 300 genes were down-regulated at 3 days post-exposure and 10 days post-exposure, respectively. The differentially expressed genes were related to toxicological response, oxidative stress and the metabolism of proteins and fats. Of these genes, most genes up-regulated at the early stage of exposure tended to be constantly down-regulated at the later stage whereas the landscape of the up- or down-regulated genes differed significantly at the two time points investigated. Functional enrichment analyses show that RNA-seq yields more insight into the biological mechanisms related to the toxic effects caused by BaP, i.e., two to fivefold more affected pathways and biological processes. Besides, we observed a change in the expression of ten genes which are important and differentially-expressed detoxification-related genes, and this was subsequently confirmed via quantitative real-time PCR. Our results provide evidence that RNA-seq is a powerful tool for toxicology and is capable of generating novel and valuable information at the transcriptome level for characterizing deleterious effects caused by BaP. PMID:25194896

  17. Effect of ageing on benzo[a]pyrene extractability in contrasting soils

    International Nuclear Information System (INIS)

    Highlights: • In vitro assessment of B[a]P in contaminated soils using 4 different methods. • An exponential kinetic model fits well with the extractability data. • Fitting parameter and 14C residue correlates with key soil properties. • Fractionation of B[a]P was obtained based on extractability by extractants. - Abstract: Changes in benzo[a]pyrene (B[a]P) extractability over 160 days ageing in four contrasting soils varying in organic matter content and clay mineralogy were investigated using dichloromethane: acetone 1:1 (DCM/Ace), 60 mM hydroxypropyl-β-cyclodextrin (HPCD) solution, 1-butanol (BuOH) and Milli-Q water. The B[a]P extractability by the four methods decreased with ageing and a first-order exponential model could be used to describe the kinetics of release. Correlation of the kinetic rate constant with major soil properties showed a significant effect of clay and sand contents and pore volume fraction (<6 nm) on sequestration of the desorbable fraction (by HPCD) and the water-extractable fraction. Analysis of 14C-B[a]P in soils after ageing showed a limited loss of B[a]P via degradation. Fractionation of B[a]P pools associated with the soil matrix was analysed according to extractability of B[a]P by the different extraction methods. A summary of the different fractions is proposed for the illustration of the effect of ageing on different B[a]P-bound fractions in soils. This study provides a better understanding of the B[a]P ageing process associated with different fractions and also emphasises the extraction capacity of the different methods employed

  18. Effect of the Apulia air quality plan on PM10 and benzo(apyrene exceedances

    Directory of Open Access Journals (Sweden)

    L. Trizio

    2016-03-01

    Full Text Available During the last years, several exceedances of PM10 and benzo(apyrene limit values exceedances were recorded in Taranto, a city in southern Italy included in so-called areas at high risk of environmental crisis because of the presence of a heavy industrial district including the largest steel factory in Europe. A study of these critical pollution events showed a close correlation with the wind coming from the industrial site to the adjacent urban area. During 2011, at monitoring sites closes to the industrial area, at least the 65% of PM10 exceedances were related to wind day conditions (characterized by at least 3 consecutive hours of wind coming from 270-360±2deg with an associated speed higher than 7 m/s. For this reason, in 2012 an integrated environmental permit and a regional air quality plan were enacted to reduce pollutant emissions from industrial plants. A study of PM10 levels registered during windy days was performed during critical episodes of pollution highlighting that the difference between windy days and no windy days’ concentrations reduces from 2012 to 2014 in industrial site. False negative events (verified ex-post by observed meteorological data not identified by the forecast model - did not show a significant influence on PM concentration: PM10 values were comparable and sometimes lower than windy days levels. It is reasonable that the new scenario with a relevant reduction emissions form Ilva plant reduced the pollutants contribution from industrial area, contributing to PM10 levels decrease, also in false negative events.

  19. Effect of ageing on benzo[a]pyrene extractability in contrasting soils

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Luchun [CERAR-Centre for Environmental Risk Assessment and Remediation and Cooperative Research Centre for Contamination Assessment and Remediation of the Environment (CRC CARE), Building X, University of South Australia, Mawson Lakes, SA 5095 (Australia); Naidu, Ravi, E-mail: Ravi.Naidu@newcastle.edu.au [CERAR-Centre for Environmental Risk Assessment and Remediation and Cooperative Research Centre for Contamination Assessment and Remediation of the Environment (CRC CARE), Building X, University of South Australia, Mawson Lakes, SA 5095 (Australia); Liu, Yanju; Palanisami, Thavamani; Dong, Zhaomin; Mallavarapu, Megharaj [CERAR-Centre for Environmental Risk Assessment and Remediation and Cooperative Research Centre for Contamination Assessment and Remediation of the Environment (CRC CARE), Building X, University of South Australia, Mawson Lakes, SA 5095 (Australia); Semple, Kirk T. [Lancaster Environment Centre, Lancaster University, Lancaster LA1 4YQ (United Kingdom)

    2015-10-15

    Highlights: • In vitro assessment of B[a]P in contaminated soils using 4 different methods. • An exponential kinetic model fits well with the extractability data. • Fitting parameter and {sup 14}C residue correlates with key soil properties. • Fractionation of B[a]P was obtained based on extractability by extractants. - Abstract: Changes in benzo[a]pyrene (B[a]P) extractability over 160 days ageing in four contrasting soils varying in organic matter content and clay mineralogy were investigated using dichloromethane: acetone 1:1 (DCM/Ace), 60 mM hydroxypropyl-β-cyclodextrin (HPCD) solution, 1-butanol (BuOH) and Milli-Q water. The B[a]P extractability by the four methods decreased with ageing and a first-order exponential model could be used to describe the kinetics of release. Correlation of the kinetic rate constant with major soil properties showed a significant effect of clay and sand contents and pore volume fraction (<6 nm) on sequestration of the desorbable fraction (by HPCD) and the water-extractable fraction. Analysis of {sup 14}C-B[a]P in soils after ageing showed a limited loss of B[a]P via degradation. Fractionation of B[a]P pools associated with the soil matrix was analysed according to extractability of B[a]P by the different extraction methods. A summary of the different fractions is proposed for the illustration of the effect of ageing on different B[a]P-bound fractions in soils. This study provides a better understanding of the B[a]P ageing process associated with different fractions and also emphasises the extraction capacity of the different methods employed.

  20. Alterations of rat liver mitochondrial oxidative phosphorylation and calcium uptake by benzo[a]pyrene

    International Nuclear Information System (INIS)

    We report that oxidative phosphorylation and Ca2+ uptake processes are enhanced in liver mitochondria isolated from benzo[a]pyrene (B[a]P)-treated rats. The carcinogen did not affect either the respiratory control index or the Ca2+ control ratio. B[a]P treatment increased the oxidation rate of several substrates that donate electrons at the level of all three coupling sites, either the ADP- or Ca2+-stimulated rates or those observed after ADP or Ca2+ exhaustion. However, the efficiency of energy coupling was maintained because both ADP/O and Ca2+/site ratios remained unchanged. The electron flow through NADH-oxidase, NADH-duroquinone reductase, NADH-juglone reductase, NADH-cytochrome c reductase, succinate-cytochrome c reductase, and cytochrome c oxidase was enhanced by B[a]P; however, succinate dehydrogenase activity was not affected. All these effects depended on the time post B[a]P administration, with a greater increase close to 48 h after administration of the carcinogen. The contents of cytochromes b, c1, and a + a3 from liver mitochondria, especially those isolated 48 h after B[a]P, were also significantly increased, although cytochrome c levels was just lightly increased 24 h after B[a]P treatment. These results suggest that B[a]P treatment stimulates mitochondrial respiration by increasing the level of several components of the mitochondrial respiratory chain. This may reflect mitochondrial adaptation to the cellular energy requirements of cell division in the neoplastic transformation process

  1. Loss of VHL in RCC reduces repair and alters cellular response to benzo[a]pyrene

    Directory of Open Access Journals (Sweden)

    MartenSchults

    2013-10-01

    Full Text Available Mutations of the von Hippel-Lindau (VHL tumor suppressor gene occur in the majority of sporadic renal-cell carcinomas (RCC. Loss of VHL function is associated with stabilization of hypoxia-inducible factor α (HIFα. We and others demonstrated that there is a two-way interaction between the aryl hydrocarbon receptor, which is an important mediator in the metabolic activation and detoxification of carcinogens, and the HIF1-pathway leading to an increased genetic instability when both pathways are simultaneously activated. The aim of this study was to investigate how environmental carcinogens, such as benzo[a]pyrene (BaP, which can be metabolically activated to BaP-7,8-diOH-9,10-epoxide (BPDE play a role in the etiology of renal-cell carcinomas (RCC. We exposed VHL deficient RCC4 cells, in which HIFα is stabilized regardless of oxygen tension, to 0.1µM BaP for 18 hours. The mutagenic BPDE-DNA adduct levels were increased in HIFα stabilized cells. Using qRT-PCR, we demonstrated that absence of VHL significantly induced the mRNA levels of AhR downstream target CYP1A1. Furthermore, HPLC analysis indicated that loss of VHL increased the concentration of BaP-7,8-dihydroxydiol, the pre-cursor metabolite of BPDE. Interestingly, the capacity to repair BPDE-DNA adducts in the HIFα stabilized RCC4 cells, was markedly reduced. Taken together, these data indicate that loss of VHL affects BaP-mediated genotoxic responses in renal-cell carcinoma and decreases repair capacity.

  2. The aryl hydrocarbon receptor nuclear translocator (Arnt) is required for tumor initiation by benzo[a]pyrene

    OpenAIRE

    Shi, Shengli; Yoon, Diana Y.; Hodge-Bell, Kimberly C.; Bebenek, Ilona G.; Whitekus, Michael J.; Zhang, Ruixue; Cochran, Alistair J.; Huerta-Yepez, Sara; Yim, Sun-Hee; Gonzalez, Frank J; Jaiswal, Anil K.; Hankinson, Oliver

    2009-01-01

    Benzo[a]pyrene (B[a]P) is a ligand for the aryl hydrocarbon receptor (Ahr). After binding ligand, Ahr dimerizes with the aryl hydrocarbon receptor nuclear translocator (Arnt) protein, and the dimer upregulates the transcription of Cyp1a1, Cyp1b1 and other enzymes involved in the metabolic activation of B[a]P. Arnt null mice die in utero. Mice in which Arnt deletion occurs constitutively in the epidermis die perinatally. In the current study, mice were developed in which the Arnt gene could be...

  3. Degradation of benzo[a]pyrene in an experimentally contaminated paddy soil by vetiver grass (Vetiveria zizanioides).

    Science.gov (United States)

    Li, H; Luo, Y M; Song, J; Wu, L H; Christie, P

    2006-01-01

    A pot experiment was conducted to study the effect of growing vetiver grass on the biodegradation of benzo[a]pyrene (B[a]P) under glasshouse conditions. Plant biomass, microbial biomass C and degradation of B[a]P were determined. B[a]P disappeared faster in the plant treatments than in unplanted controls. Disappearance of B[a]P was accompanied by an increase in soil microbial biomass C. Vetiver grass may promote the biodegradation of B[a]P under flooded conditions by plant roots by stimulating the microbial biomass. Microbial biomass was the main factor affecting dissipation of B[a]P under flooded conditions. PMID:16528581

  4. Electrochemiluminescent Arrays for Cytochrome P450-Activated Genotoxicity Screening. DNA Damage from Benzo[a]pyrene Metabolites

    OpenAIRE

    Hvastkovs, Eli G.; So, Minjeong; Krishnan, Sadagopan; Bajrami, Besnik; Tarun, Maricar; Jansson, Ingela; Schenkman, John B.; Rusling, James F.

    2007-01-01

    Arrays suitable for genotoxicity screening are reported that generate metabolites from cytochrome P450 enzymes (CYPs) in thin-film spots. Array spots containing DNA, various human cyt P450s, and electrochemiluminescence (ECL) generating metallopolymer [Ru(bpy)2PVP10]2+ were exposed to H2O2 to activate the enzymes. ECL from all spots was visualized simultaneously using a CCD camera. Using benzo[a]pyrene as a test substrate, enzyme activity for producing DNA damage in the arrays was found in th...

  5. Total synthesis of cis-hydroazulene sesquiterpenes. Base-induced and -directed elimination and rearrangement reactions of perhydronaphthalene-1,4-diol monosulfonate esters.

    NARCIS (Netherlands)

    Jenniskens, L.H.D.

    1992-01-01

    The total synthesis of a number of cis-fused hydroazulene sesquiterpenes is described in this thesis. In this synthetic study, ample attention is paid to the mechanistic aspects of the base- induced and -directed rearrangement and elimination reactions of perhydronaphthalene-1,4-diol monosulfonate e

  6. (E-2-((4R,5R-5-((Benzyloxymethyl-2,2-dimethyl-1,3-dioxolan-4-ylbut-2-ene-1,4-diol

    Directory of Open Access Journals (Sweden)

    Carlos R. Carreras

    2010-04-01

    Full Text Available The synthesis of (E-2-((4R,5R-5-((benzyloxymethyl-2,2-dimethyl-1,3-dioxolan-4-ylbut-2-ene-1,4-diol by a one-step reduction of the appropriate 2-substituted butenolide is reported. Product characterization was carried out by IR, 1H NMR, 13C NMR, MS, elemental analysis and optical rotation.

  7. Crystallization and preliminary X-ray analysis of molecular chaperone-like diol dehydratase-reactivating factor in ADP-bound and nucleotide-free forms

    International Nuclear Information System (INIS)

    The molecular chaperone-like reactivating factor for adenosylcobalamin (coenzyme B12) dependent diol dehydratase was crystallized in ADP-bound and nucleotide-free forms. Preliminary X-ray analysis indicated that crystals are orthorhombic and diffract to 2.0 Å. Adenosylcobalamin (coenzyme B12) dependent diol dehydratase (EC 4.2.1.28) catalyzes the conversion of 1,2-diols and glycerol to the corresponding aldehydes. It undergoes mechanism-based inactivation by glycerol. The diol dehydratase-reactivating factor (DDR) reactivates the inactivated holoenzymes in the presence of adenosylcobalamin, ATP and Mg2+ by mediating the release of a damaged cofactor. This molecular chaperone-like factor was overexpressed in Escherichia coli, purified and crystallized in the ADP-bound and nucleotide-free forms by the sandwich-drop vapour-diffusion method. The crystals of the ADP-bound form belong to the orthorhombic system, with space group P212121 and unit-cell parameters a = 83.26, b = 84.60, c = 280.09 Å, and diffract to 2.0 Å. In the absence of nucleotide, DDR crystals were orthorhombic, with space group P212121 and unit-cell parameters a = 81.92, b = 85.37, c = 296.99 Å and diffract to 3.0 Å. Crystals of both forms were suitable for structural analysis

  8. Fluorine-containing terpene analogs. IV. 9,9,9,10,10,10-Hexafluoro-p-menthane-1,8-diol (hexafluoroterpine)

    Energy Technology Data Exchange (ETDEWEB)

    Zalesskaya, I.M.; Fialkov, Yu.A.; Parakhnenko, A.I.; Yagupol' skii, I.M.

    1988-03-10

    The oxidation of trans-e,e-4-(2-hydroxyperfluoroisopropyl)cyclohexanol with pyridinium chlorochromate gave the corresponding cyclohexanone. The reaction of this product with methylmagnesium iodide gave cis- and trans-9,9,9,10,10,10-hexafluoro-p-menthane-1,8-diol, which is fluorinated analog of natural terpine.

  9. Alternating polyesteramides based on 1,4-butylene terephthalamide: 3. Alternating polyesteramides based on mixtures of linear diols (4NTm,p)

    NARCIS (Netherlands)

    Serrano, P.J.M.; Werff, van der B.A.; Gaymans, R.J.

    1998-01-01

    Strictly alternating polyesteramides consisting of 1,4-butylene terephthalamide diester and mixtures of aliphatic diols have been synthesised in the melt in the presence of a titanium catalyst. To increase the molecular weight a solid state post condensation was applied. The composition was determin

  10. SEPARATION OF 32P-LABELED 3',5'-BISPHOSPHATE NUCLEOTIDES OF POLYCYCLIC AROMATIC HYDROCARBON ANTI-DIOL-EPOXIDES AND DERIVATIVES

    Science.gov (United States)

    23P-Postlabeling/HPLC is a highly sensitive analytical method for identification of chemical-modified DNA adducts isolated from experimental animals and human samples. o determine the optimal 32P-postlabeling/HPLC conditions for efficient separation, we employed ten diol-epoxide-...

  11. Effects of 3-beta-diol, an androgen metabolite with intrinsic estrogen-like effects, in modulating the aquaporin-9 expression in the rat efferent ductules

    Directory of Open Access Journals (Sweden)

    Hess Rex A

    2006-10-01

    Full Text Available Abstract Background Fluid homeostasis is critical for normal function of the male reproductive tract and aquaporins (AQP play an important role in maintenance of this water and ion balance. Several AQPs have been identified in the male, but their regulation is not fully comprehended. Hormonal regulation of AQPs appears to be dependent on the steroid in the reproductive tract region. AQP9 displays unique hormonal regulation in the efferent ductules and epididymis, as it is regulated by both estrogen and dihydrotestosterone (DHT in the efferent ductules, but only by DHT in the initial segment epididymis. Recent data have shown that a metabolite of DHT, 5-alpha-androstane-3-beta-17-beta-diol (3-beta-diol, once considered inactive, is also present in high concentrations in the male and indeed has biological activity. 3-beta-diol does not bind to the androgen receptor, but rather to estrogen receptors ER-alpha and ER-beta, with higher affinity for ER-beta. The existence of this estrogenic DHT metabolite has raised the possibility that estradiol may not be the only estrogen to play a major role in the male reproductive system. Considering that both ER-alpha and ER-beta are highly expressed in efferent ductules, we hypothesized that the DHT regulation of AQP9 could be due to the 3-beta-diol metabolite. Methods To test this hypothesis, adult male rats were submitted to surgical castration followed by estradiol, DHT or 3-beta-diol replacement. Changes in AQP9 expression in the efferent ductules were investigated by using immunohistochemistry and Western blotting assay. Results Data show that, after castration, AQP9 expression was significantly reduced in the efferent ductules. 3-beta-diol injections restored AQP9 expression, similar to DHT and estradiol. The results were confirmed by Western blotting assay. Conclusion This is the first evidence that 3-beta-diol has biological activity in the male reproductive tract and that this androgen metabolite has

  12. The genotoxic effects of benzo[a]pyrene and methamidophos on black porgy evaluated by comet assay

    Science.gov (United States)

    Liu, Rixian; Hong, Huasheng; Wang, Xinhong; Wang, Kejian; Wang, Chunguang

    2005-12-01

    In this study, two common pollutants (benzo[a]pyrene and methamidophos) in marine environment were tested by comet assay for their inducement of in vivo genotoxic effect to the blood cells of black porgy ( Acanthopagrus schlegeli). The fish was exposed to 2 μg/L of benzo[a]pyrene (BaP) and methamidophos, and their mixture. The assay was performed on whole blood at 2 h, 5 h, 24 h and 96 h exposure intervals. A significant increase in DNA damage was observed in each treatment with the pollutants. Additive effect of BaP and methamidophos was also found in the experiment. However, the decrease ratios of DNA damage for 5 h and 96 h exposure interals compared with 2 h and 24 h exposure ones, respectively, were noticed. This phenomenon may be explained by the function of repairing process via enzyme cytochrome P450 in the animal. Evidence of the genotoxicity of organophosphorus pesticides (OPs) and polynuclear aromatic hydrocarbons (PAHs) on marine fish are discussed in this paper.

  13. Determination of Benzo(a)pyrene in Malaysian commercialized coffee powder using solid phase extraction and gas chromatography

    International Nuclear Information System (INIS)

    Roasting is a critical process in coffee production as it enables the development of flavor and aroma. Benzo[a]pyrene (BaP) is a non desirable product of incomplete combustion at temperatures between 300 and 600 degree Celsius and may be produced during roasting step. In this study, selected samples of roasted coffee powder were analysed for BaP. Extraction of BaP was achieved using C18 solid phase extraction (SPE) prior to analysis by gas chromatography. Calibration curve prepared with concentrations ranged between 3 - 50 ppm showed good linearity with r = 0.999. The limit of detection (LOD) was 0.25 ppm and the limit of quantification (LOQ) was 0.85 ppm. Recovery of BaP obtained from spiked sample (3 ppm) was 88.7 % with RSD (n=3) of 5.4 %. Benzo[a]pyrene was detected in all samples, at level ranging from 0.14 to 0.62 ppb. (author)

  14. The genotoxic effects of benzo[a]pyrene and methamidophos on black porgy evaluated by comet assay

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    In this study, two common pollutants (benzo[a]pyrene and methamidophos) in marine environment were tested by comet assay for their inducement of in vivo genotoxic effect to the blood cells of black porgy (Acanthopagrus schlegeli). The fish was exposed to 2 μg/L of benzo[a]pyrene (BaP) and methamidophos, and their mixture. The assay was performed on whole blood at 2 h, 5 h, 24 h and 96 h exposure intervals. A significant increase in DNA damage was observed in each treatment with the pollutants. Additive effect of BaP and methamidophos was also found in the experiment. However, the decrease ratios of DNA damage for 5 h and 96 h exposure interals compared with 2 h and 24 h exposure ones, respectively, were noticed. This phenomenon may be explained by the function of repairing process via enzyme cytochrome P450 in the animal. Evidence of the genotoxicity of organophosphorus pesticides (OPs) and polynuclear aromatic hydrocarbons (PAHs) on marine fish are discussed in this paper.

  15. A common carcinogen benzo[a]pyrene causes neuronal death in mouse via microglial activation.

    Directory of Open Access Journals (Sweden)

    Kallol Dutta

    Full Text Available BACKGROUND: Benzo[a]pyrene (B[a]P belongs to a class of polycyclic aromatic hydrocarbons that serve as micropollutants in the environment. B[a]P has been reported as a probable carcinogen in humans. Exposure to B[a]P can take place by ingestion of contaminated (especially grilled, roasted or smoked food or water, or inhalation of polluted air. There are reports available that also suggests neurotoxicity as a result of B[a]P exposure, but the exact mechanism of action is unknown. METHODOLOGY/PRINCIPAL FINDINGS: Using neuroblastoma cell line and primary cortical neuron culture, we demonstrated that B[a]P has no direct neurotoxic effect. We utilized both in vivo and in vitro systems to demonstrate that B[a]P causes microglial activation. Using microglial cell line and primary microglial culture, we showed for the first time that B[a]P administration results in elevation of reactive oxygen species within the microglia thereby causing depression of antioxidant protein levels; enhanced expression of inducible nitric oxide synthase, that results in increased production of NO from the cells. Synthesis and secretion of proinflammatory cytokines were also elevated within the microglia, possibly via the p38MAP kinase pathway. All these factors contributed to bystander death of neurons, in vitro. When administered to animals, B[a]P was found to cause microglial activation and astrogliosis in the brain with subsequent increase in proinflammatory cytokine levels. CONCLUSIONS/SIGNIFICANCE: Contrary to earlier published reports we found that B[a]P has no direct neurotoxic activity. However, it kills neurons in a bystander mechanism by activating the immune cells of the brain viz the microglia. For the first time, we have provided conclusive evidence regarding the mechanism by which the micropollutant B[a]P may actually cause damage to the central nervous system. In today's perspective, where rising pollution levels globally are a matter of grave concern, our

  16. Monolayer behaviour of chiral compounds at the air-water interface: 4-hexadecyloxy-butane-1,2-diol

    DEFF Research Database (Denmark)

    Rietz, R.; Rettig, W.; Brezesinski, G.;

    1996-01-01

    Monolayers of the pure S-enantiomer (x(S) = 1) and of two mixtures x(S) = 0.75 and x(S) = 0.5 (racemate) of 4-hexadecyloxy-butane-1,2-diol (C16H33-O-CH2-CH2-CHOH-CH2OH) (HOBD) have been studied at the air-water interface by thermodynamic measurements, fluorescence microscopy and X-ray diffraction....... The isotherms depend only slightly on chirality. Above the transition pressure pi(c) condensed domains with a polygonal shape are formed. In all cases the domains start to destabilize from the notch. The branches of the S-enantiomer turn only clockwise, whereas domains of the mixtures show branches...

  17. Synthesis, Properties and Applications of Biodegradable Polymers Derived from Diols and Dicarboxylic Acids: From Polyesters to Poly(ester amides

    Directory of Open Access Journals (Sweden)

    Angélica Díaz

    2014-04-01

    Full Text Available Poly(alkylene dicarboxylates constitute a family of biodegradable polymers with increasing interest for both commodity and speciality applications. Most of these polymers can be prepared from biobased diols and dicarboxylic acids such as 1,4-butanediol, succinic acid and carbohydrates. This review provides a current status report concerning synthesis, biodegradation and applications of a series of polymers that cover a wide range of properties, namely, materials from elastomeric to rigid characteristics that are suitable for applications such as hydrogels, soft tissue engineering, drug delivery systems and liquid crystals. Finally, the incorporation of aromatic units and α-amino acids is considered since stiffness of molecular chains and intermolecular interactions can be drastically changed. In fact, poly(ester amides derived from naturally occurring amino acids offer great possibilities as biodegradable materials for biomedical applications which are also extensively discussed.

  18. In vitro investigations of α-amylase mediated hydrolysis of cyclodextrins in the presence of ibuprofen, flurbiprofen, or benzo[a]pyrene

    DEFF Research Database (Denmark)

    Riisager, Ludmilla Lumholdt; Holm, R.; Jørgensen, E. B.;

    2012-01-01

    -γ-cyclodextrins have different biopharmaceutical behaviours than the other evaluated cyclodextrins. The rate of degradation was affected by the addition of the inclusion complex forming additives flurbiprofen, ibuprofen and benzo[a]pyrene. This effect between the degradation dynamics and the included additives was...

  19. Metabolism of benzo(a)pyrene and identification of the major benzo(a)pyrene-DNA adducts in cultured human colon

    DEFF Research Database (Denmark)

    1978-01-01

    The metabolism of benzo(a)pyrene in cultured human colon has been investigated. Nontumorous colonie tissue was collected at the time of either surgery or "immediate autopsy" from patients with or without colonic cancer. After 24 hr in culture the expiants were exposed to [3H]benzo(a)pyrene for an...... can metabolize benzo(a)pyrene by pathways similar to those found in human bronchus and in cells of experimental animals....... acid increased the binding levels of benzo(a)pyrene to DNA. An increased level of frans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene in the culture media was also observed when expiants were coincubated with either taurodeoxycholic acid or lithocholic acid. These results indicate that cultured human colon......The metabolism of benzo(a)pyrene in cultured human colon has been investigated. Nontumorous colonie tissue was collected at the time of either surgery or "immediate autopsy" from patients with or without colonic cancer. After 24 hr in culture the expiants were exposed to [3H]benzo(a)pyrene for...

  20. Benzo[a]pyrene contamination in Rostov Region of Russian Federation: A 10-year retrospective of soil monitoring under the effect of long-term technogenic pollution

    Directory of Open Access Journals (Sweden)

    Svetlana Sushkova

    2016-04-01

    Full Text Available The aim of the current work was to study the main tendencies in the accumulation and distribution of benzo[a]pyrene in soils of the affected zone of the Novocherkassk regional power plant. Studies were conducted on the soils of monitoring plots subjected to Novocherkassk regional power plant emissions. Monitoring plots were established at different distances from the Novocherkassk regional power plant (1.0–20.0 km. Regularities in the accumulation and distribution of benzo[a]pyrene in chernozemic, meadow-chernozemic, and alluvial soils under the effect of aerotechnogenic emissions from the Novocherkassk regional power plant have been revealed on the basis of long-term monitoring studies (from 2002 to 2011. The tendencies in the distribution and accumulation of BaP in the studied soils coincided during the 10 years of monitoring studies. It has been found the 5-km zone to the northwest from the power station, which coincides with the predominant wind direction, is most subjected to contamination by benzo[a]pyrene, with the maximum accumulation at a distance of about 1.6 km from the source. Dynamics of pollutant accumulation in soils depends on number of Novocherkassk regional power plant emissions. The content of benzo[a]pyrene in the soil is an indicator of the technogenic load impact on the areas, for which the combustion products of hydrocarbon fuel are the major pollutants. A gradual decrease of the pollutant content in the soils was revealed during the period from 2002 to 2011. It explained by the significant decrease in the volume of pollutant emissions from the plant and the self-purification capacity of soils and mechanisms of benzo[a]pyrene degradation.

  1. Benzo(a)pyrene accumulation in soils of technogenic emission zone by subcritical water extraction method

    Science.gov (United States)

    Sushkova, Svetlana; Minkina, Tatiana; Kizilkaya, Ridvan; Mandzhieva, Saglara; Batukaev, Abdulmalik; Bauer, Tatiana; Gulser, Coskun

    2016-04-01

    The purpose of research is the assessment of main marker of polycyclic aromatic hydrocarbons contamination, benzo[a]pyrene (BaP) content in soils of emission zone of the power complex plant in soils with use of ecologically clean and effective subcritical water extraction method. Studies were conducted on the soils of monitoring plots subjected to Novocherkassk Power Plant emissions from burning coal. In 2000, monitoring plots were established at different distances from the NPS (1.0-20.0 km). Soil samples for the determination of soil properties and the contents of BaP were taken from a depth of 0-20 cm. The soil cover in the region under study consisted of ordinary chernozems, meadow-chernozemic soils, and alluvial meadow soils. This soil revealed the following physical and chemical properties: Corg-3.1-5.0%, pH-7.3-7.6, ECE-31.2-47.6 mmol(+)/100g; CaCO3-0.2-1.0%, the content of physical clay - 51-67% and clay - 3-37%. BaP extraction from soils was carried out by a subcritical water extraction method. Subcritical water extraction of BaP from soil samples was conducted in a specially developed extraction cartridge made of stainless steel and equipped with screw-on caps at both ends. It was also equipped with a manometer that included a valve for pressure release to maintain an internal pressure of 100 atm. The extraction cartridge containing a sample and water was placed into an oven connected to a temperature regulator under temperature 250oC and pressure 60 atm. The BaP concentration in the acetonitrile extract was determined by HPLC. The efficiency of BaP extraction from soil was determined using a matrix spike. The main accumulation of pollutant in 20 cm layer of soils is noted directly in affected zone on the plots situated at 1.2, 1.6, 5.0, 8.0 km from emission source in the direction of prevailing winds. The maximum quantity of a pollutant was founded in the soil of the plot located mostly close to a source of pollution in the direction of prevailing winds

  2. Electrochemiluminescent Arrays for Cytochrome P450-Activated Genotoxicity Screening. DNA Damage from Benzo[a]pyrene Metabolites

    Science.gov (United States)

    Hvastkovs, Eli G.; So, Minjeong; Krishnan, Sadagopan; Bajrami, Besnik; Tarun, Maricar; Jansson, Ingela; Schenkman, John B.; Rusling, James F.

    2007-01-01

    Arrays suitable for genotoxicity screening are reported that generate metabolites from cytochrome P450 enzymes (CYPs) in thin-film spots. Array spots containing DNA, various human cyt P450s, and electrochemiluminescence (ECL) generating metallopolymer [Ru(bpy)2PVP10]2+ were exposed to H2O2 to activate the enzymes. ECL from all spots was visualized simultaneously using a CCD camera. Using benzo[a]pyrene as a test substrate, enzyme activity for producing DNA damage in the arrays was found in the order CYP1B1 > CYP1A2 > CYP1A1 > CYP2E1 > myoglobin, the same as the order of their metabolic activity. Thus, these arrays estimate the relative propensity of different enzymes to produce genotoxic metabolites. This is the first demonstration of ECL arrays for high-throughput in vitro genotoxicity screening. PMID:17261025

  3. EROD activity and genotoxicity in the seabob shrimp Xiphopenaeus kroyeri exposed to benzo[a]pyrene (BaP) concentrations.

    Science.gov (United States)

    da Silva Rocha, Arthur José; Gomes, Vicente; Rocha Passos, Maria José de Arruda Campos; Hasue, Fabio Matsu; Alves Santos, Thaís Cruz; Bícego, Márcia Caruso; Taniguchi, Satie; Van Ngan, Phan

    2012-11-01

    Seabob shrimp Xiphopenaeus kroyeri is a marine species that lives in shallow waters of coastal environments, often impacted by polycyclic aromatic hydrocarbons (PAH) pollution. In the present study, seabob shrimp were exposed for 96 h to benzo[a]pyrene (BaP) at the nominal concentrations of 100, 200, 400 and 800 microg-L(-1). Animals of the control groups were exposed either to clean water or to the BaP-carrier (DMSO). At the end of the exposures, muscle tissues were sampled for BaP uptake assessment and hepatopancreas and hemolymph for EROD enzyme activity and hemocytes DNA damage, respectively. EROD activity and DNA damage increased significantly as a function of BaP exposure concentrations. Significant correlations between BaP uptake and both EROD activity and DNA damage suggest that they can be used as suitable tools for integrated levels of study on the biomarkers of PAH exposure. PMID:22974795

  4. Phase behavior and crystal structure of 3-(1-naphthyloxy)- and 3-(4-indolyloxy)-propane-1,2-diol, synthetic precursors of chiral drugs propranolol and pindolol

    Science.gov (United States)

    Bredikhin, Alexander A.; Gubaidullin, Aidar T.; Bredikhina, Zemfira A.; Fayzullin, Robert R.; Samigullina, Aida I.; Zakharychev, Dmitry V.

    2013-08-01

    Valuable precursors of popular chiral drugs propranolol and pindolol, 3-(1-naphthyloxy)-propane-1,2-diol 3 and 3-(4-indolyloxy)-propane-1,2-diol 4 were investigated by IR spectroscopy, DSC, and X-ray diffraction methods. Both compounds, crystallizing from enantiopure feed material, form "guaifenesin-like" crystal packing in which the classic H-bonded bilayers, framed in both sides by hydrophobic fragments of the molecules, acts as the basic crystal-forming motif. Diol 4 prone to spontaneous resolution and conserves its packing pattern crystallizing from racemate. Under the same conditions, diol 3 forms weakly stable solid racemic compound. Some reasons for such a behavior are identified and discussed.

  5. Antioxidant responses to benzo[a]pyrene and Aroclor 1254 exposure in the green-lipped mussel, Perna viridis

    International Nuclear Information System (INIS)

    In this study, the green-lipped mussel, Perna viridis (L.), was exposed to two concentrations of benzo[a]pyrene (B[a]P) (0.3 μg l-1; 3 μg l-1) and two concentrations of Aroclor 1254 (0.5 μg l-1; 5 μg l-1). In addition, a mixture of the contaminants was used (0.3 μg l-1 B[a]P+0.5 μg l-1 Aroclor 1254; 3 μg l-1 B[a]P+5 μg l-1 Aroclor 1254). All concentrations were nominal. A suite of enzymes [glutathione S transferase (GST), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR)], glutathione (GSH) level and lipid peroxidation (LPO) in the mussel gill and hepatopancreas were monitored over 18 days. CAT and GSH in gill tissue were positively correlated with concentration of Aroclor 1254. Activity of hepatic GST and SOD was significantly related to body burden of Aroclor 1254. LPO, GR and GPx in gill and hepatopancreas and hepatic GST were positively correlated with B[a]P concentration. The results indicate the importance of using biomarkers specific to the type of contaminant(s) that are likely to be present. Controlled laboratory experiments, such as this study, are useful in ascertaining biomarkers suitable for use with complex contaminant mixtures in the marine environment. - Benzo[a]pyrene and Aroclor 1254 separately and in combination caused specific induction in a number of antioxidant parameters in the gill and hepatopancreas of green-lipped mussels

  6. Supramolecular Arrangement in Styphnic Acid and Naphthalene-1,4-diol (1 : 1 through a Novel Synthetic Rote for Styphnic Acid

    Directory of Open Access Journals (Sweden)

    Moamen S. Refat

    2013-01-01

    Full Text Available The chemical preparation and crystal structure of styphnic acid and naphthalene-1,4-diol (1 : 1 (I have been reported. The compound crystallizes in the orthorhombic system in space group Pnma and cell parameters a=6.6712(2, b=16.8267(7, c=13.6450(5 Å and V=1531.71(10 Å3, and Z=4. Crystal structure has been determined and refined to R=0.0576. The crystal structure of I, the asymmetric unit, contains C6H2N3O7, C10H7O, and it is a half portion of both styphnic acid and naphthalene-1,4-diol. The O1–H1⋯O2 intramolecular hydrogen bond was found between the O–H and a nitro group in the styphnic acid unit.

  7. Characterization of the SgcF epoxide hydrolase supporting an (R)-vicinal diol intermediate for enediyne antitumor antibiotic C-1027 biosynthesis.

    Science.gov (United States)

    Lin, Shuangjun; Horsman, Geoffrey P; Chen, Yihua; Li, Wenli; Shen, Ben

    2009-11-18

    C-1027 is a chromoprotein antitumor antibiotic consisting of an apoprotein and the C-1027 chromophore. The C-1027 chromophore possesses four distinct structural moieties-an enediyne core, a deoxy aminosugar, a benzoxazolinate, and an (S)-3-chloro-5-hydroxy-beta-tyrosine-the latter two of which are proposed to be appended to the enediyne core via a convergent biosynthetic strategy. Here we report the in vitro characterization of SgcF, an epoxide hydrolase from the C-1027 biosynthetic gene cluster that catalyzes regio- and stereospecific hydrolysis of styrene oxide, serving as an enediyne core epoxide intermediate mimic, to form a vicinal diol. Abolishment of C-1027 production in the DeltasgcF mutant strain Streptomyces globisporus SB1010 unambiguously establishes that sgcF plays an indispensable role in C-1027 biosynthesis. SgcF efficiently hydrolyzes (S)-styrene oxide, displaying an apparent K(m) of 0.6 +/- 0.1 mM and k(cat) of 48 +/- 1 min(-1), via attack at the alpha-position to exclusively generate the (R)-phenyl vicinal diol, consistent with the stereochemistry of the C-1027 chromophore. These findings support the role of SgcF in the proposed convergent pathway for C-1027 biosynthesis, unveiling an (R)-vicinal diol as a key intermediate. Interestingly, SgcF can also hydrolyze (R)-styrene oxide to afford preferentially the (R)-phenyl vicinal diol via attack at the beta-position, albeit with significantly reduced efficiency (apparent K(m) of 2.0 +/- 0.4 mM and k(cat) = 4.3 +/- 0.3 min(-1)). Although the latter activity unlikely contributes to C-1027 biosynthesis in vivo, such enantioconvergence arising from complementary regioselective hydrolysis of a racemic substrate could be exploited to engineer epoxide hydrolases with improved regio- and/or enantiospecificity. PMID:19856960

  8. Carbonate phosphonium salts as catalysts for the transesterification of dialkyl carbonates with diols. The competition between cyclic carbonates and linear dicarbonate products.

    Science.gov (United States)

    Selva, Maurizio; Caretto, Alessio; Noè, Marco; Perosa, Alvise

    2014-06-28

    At 90-120 °C, in the presence of methylcarbonate and bicarbonate methyltrioctylphosphonium salts as catalysts ([P8881][A]; [A] = MeOCO2 and HOCO2), the transesterification of non-toxic dimethyl- and diethyl-carbonate (DMC and DEC, respectively) with 1,X-diols (2 ≤ X ≤ 6) proceeds towards the formation of cyclic and linear products. In particular, 1,2-propanediol and ethylene glycol afford propylene- and ethylene-carbonate with selectivity and yields up to 95 and 90%, respectively; while, the reaction of DMC with higher diols such 1,3-butanediol, 2-methyl-1,3-propanediol, 1,3-propanediol, 2,2-dimethyl, 1,3-propanediol, 1,4-butanediol and 1,6-hexanediol produce linear C8-C10 dicarbonates of general formula MeOC(O)O∼∼∼OC(O)OMe as the almost exclusive products. Of note, these dicarbonate derivatives are not otherwise accessible in good yields by other conventional base catalyzed methods. Among 1,3-diols, the only exception was 2-methyl 2,4-pentandiol that yields the corresponding cyclic carbonate, i.e. 4,4,6-trimethyl-1,3-dioxan-2-one. In no one case, polycarbonates are observed. Such remarkable differences of product distributions are ascribed to the structure (branching and relative position of OH groups) of diols and to the role of cooperative (nucleophilic and electrophilic) catalysis which has been proved for onium salts. The investigated carbonate salts are not only effective in amounts as low as 0.5 mol%, but they are highly stable and recyclable. PMID:24825024

  9. 2-aminopyrimidine-4,6-diol as an efficient ligand for solvent-free copper-catalyzed N-arylations of imidazoles with aryl and heteroaryl halides.

    Science.gov (United States)

    Xie, Ye-Xiang; Pi, Shao-Feng; Wang, Jian; Yin, Du-Lin; Li, Jin-Heng

    2006-10-13

    Efficient and solvent-free copper-catalyzed N-arylations of imidazoles with aryl and heteroaryl halides have been demonstrated. In the presence of CuBr, 2-aminopyrimidine-4,6-diol, and TBAF (n-Bu4NF), a variety of imidazoles underwent the N-arylation reaction with aryl and heteroaryl halides smoothly in moderate to excellent yields. Noteworthy is that the reaction is conducted under solvent-free conditions. PMID:17025338

  10. 2-Butyne-1,4-diol as a novel corrosion inhibitor for API X65 steel pipeline in carbonate/bicarbonate solution

    International Nuclear Information System (INIS)

    Highlights: ► Corrosion of API 5L X65 is effectively reduced by the addition of the inhibitor. ► The techniques include weight loss, potentiodynamic polarization, EIS and AFM. ► 2-Butyne-1,4-diol acts as a mixed-type inhibitor. ► The adsorption of 2-butyne-1,4-diol obeys Langmuir adsorption isotherm. - Abstract: The inhibition effects of 2-butyne-1,4-diol on the corrosion susceptibility of grade API 5L X65 steel pipeline in 2 M Na2CO3/1 M NaHCO3 solution were studied by electrochemical techniques and weight loss measurements. The results indicated that this inhibitor was a mixed-type inhibitor, with a maximum percentage inhibition efficiency of approximately 92% in the presence of 5 mM inhibitor. Atomic force microscopy revealed that a protective film was formed on the surface of the inhibited sample. The adsorption of the inhibitor was found to conform to the Langmuir isotherm with the standard adsorption free energy of −21.08 kJ mol−1.

  11. Preliminary neutron and ultrahigh-resolution X-ray diffraction studies of the aspartic proteinase endothiapepsin cocrystallized with a gem-diol inhibitor

    International Nuclear Information System (INIS)

    Three data sets have been collected on endothiapepsin complexed with the gem-diol inhibitor PD-135,040: a high-resolution synchrotron X-ray data set, a room-temperature X-ray data set and a neutron diffraction data set. Until recently, it has been impossible to grow large protein crystals of endothiapepsin with any gem-diol inhibitor that are suitable for neutron diffraction. Endothiapepsin has been cocrystallized with the gem-diol inhibitor PD-135,040 in a low solvent-content (39%) unit cell, which is unprecedented for this enzyme–inhibitor complex and enables ultrahigh-resolution (1.0 Å) X-ray diffraction data to be collected. This atomic resolution X-ray data set will be used to deduce the protonation states of the catalytic aspartate residues. A room-temperature neutron data set has also been collected for joint refinement with a room-temperature X-ray data set in order to locate the H/D atoms at the active site

  12. Preparation and characterization of bifunctional oxidative and acidic catalysts Nb2O5/TS-1 for synthesis of diols

    International Nuclear Information System (INIS)

    Bifunctional oxidative and acidic catalyst was prepared by incorporation of titanium ion (Ti4+) and niobic acid in zeolite molecular-sieve. The catalysts being active both in oxidation reactions due to the presence of tetrahedral Ti4+, and acid-catalyzed reactions due to the presence of niobic acid. Nb/TS-1 was prepared by hydrothermal synthesis of TS-1, calcination in air and subsequent impregnation of niobium into TS-1. The sample was characterized by XRD, FTIR, UV-vis DR, TPR and pyridine adsorption techniques. The XRD analysis of Nb/TS-1 revealed that the MFI structure of the TS-1 support was found to be intact upon incorporation of niobium. The infrared spectra showed that the tetrahedral titanium in the TS-1 is still remained after impregnation with niobium while based on the UV-vis DR result, the niobium species are in the octahedral structure. On the basis TPR and infrared of hydroxyl groups results, it is concluded that niobium species interacted with the silanols on the surface of TS-1. Pyridine adsorption study shows both Bronsted and Lewis acid sites are present in Nb/TS-1. The catalytic results in the transformation of 1-octene to 1,2-octanediol through the formation of 1,2-epoxyoctane by using Nb/TS-1 indicate that the production of epoxide and diol was correlated with the presence of oxidative and Bronsted acidic sites in the catalyst

  13. Synthesis of bio-based thermoplastic polyurethane elastomers containing isosorbide and polycarbonate diol and their biocompatible properties.

    Science.gov (United States)

    Oh, So-Yeon; Kang, Min-Sil; Knowles, Jonathan C; Gong, Myoung-Seon

    2015-09-01

    A new family of highly elastic polyurethanes (PUs) partially based on renewable isosorbide were prepared by reacting hexamethylene diisocyanate with a various ratios of isosorbide and polycarbonate diol 2000 (PCD) via a one-step bulk condensation polymerization without catalyst. The influence of the isorsorbide/PCD ratio on the properties of the PU was evaluated. The successful synthesis of the PUs was confirmed by Fourier transform-infrared spectroscopy and (1)H nuclear magnetic resonance. The resulting PUs showed high number-average molecular weights ranging from 56,320 to 126,000 g mol(-1) and tunable Tg values from -34 to -38℃. The thermal properties were determined by differential scanning calorimetry and thermogravimetric analysis. The PU films were flexible with breaking strains from 955% to 1795% at from 13.5 to 54.2 MPa tensile stress. All the PUs had 0.9-2.8% weight lost over 4 weeks and continual slow weight loss of 1.1-3.6% was observed within 8 weeks. Although the cells showed a slight lower rate of proliferation than that of the tissue culture polystyrene as a control, the PU films were considered to be cytocompatible and nontoxic. These thermoplastic PUs were soft, flexible and biocompatible polymers, which open up a range of opportunities for soft tissue augmentation and regeneration. PMID:26055962

  14. Efficiency of 1,9- Nonane-diol-diacrylate as a radiation vulcanization accelerator for natural rubber latex

    International Nuclear Information System (INIS)

    The efficiency of 1,9- Nonane-diol-diacrylate (NDDA) as a radiation vulcanization accelerator (RVA) for natural rubber latex (NRL) was investigated. Both gamma rays and electron beam (EB) were used for vulcanizing NRL with NDDA. The radiation dose of gamma rays, concentration of NDDA required to vulcanize the latex were optimized. 20 kGy radiation dose of gamma rays and 5 phr concentration of NDDA were found optimum to get maximum tensile and related properties. NRL was vulcanized under EB to find out the optimum condition of irradiation with this RVA. The defoamer concentrations, length of irradiation time under EB, concentration of RVA were optimizer by changing various parameters of the EB machine with a constant set of the others. 0.2 phr defoamer concentration, 30 minutes irradiation time and 5 phr concentration of NDDA were found optimum for irradiation of NRL under the EB machine. Effect of low current and optimum volume of latex charged in the reaction vessel suitable for vulcanization at a time were found out. (author)

  15. Analysis of Benzo[a]pyrene in Vegetable Oils Using Molecularly Imprinted Solid Phase Extraction (MISPE) Coupled with Enzyme-Linked Immunosorbent Assay (ELISA)

    OpenAIRE

    Michael Pschenitza; Rudolf Hackenberg; Reinhard Niessner; Dietmar Knopp

    2014-01-01

    This paper describes the development of a molecularly imprinted polymer-based solid phase extraction (MISPE) method coupled with enzyme-linked immunosorbent assay (ELISA) for determination of the PAH benzo[a]pyrene (B[a]P) in vegetable oils. Different molecularly imprinted polymers (MIPs) were prepared using non-covalent 4-vinylpyridine/divinylbenzene co-polymerization at different ratios and dichloromethane as porogen. Imprinting was done with a template mixture of phenanthrene and pyrene ...

  16. Benzo[a]pyrene metabolites: formation in rat liver cell-culture lines, binding to macromolecules, and mutagenesis in V79 hamster cells

    International Nuclear Information System (INIS)

    Benzo[a]pyrene was metabolized in liver cell lines derived from BD-IV and BD-VI rats which included several chemically-transformed lines (IAR-6-1; IAR-19; IAR-28), one spontaneous transformant (IAR-27) as well as one nonmalignant line (IAR-20). Cultures were treated with tritiated benzo[a]pyrene over a 5-day period. The cells and medium were extracted with ethyl acetate and the distribution between organic-soluble and water-soluble metabolites determined. Organic-soluble metabolites consisting of dihydrodiols, phenols and quinones were determined by high-pressure liquid chromatography, and macromolecular binding of BP to each cell line was measured over a 24-h period. Comparisons between binding and overall metabolism were not directly proportional in these liver cell lines. However, there was a positive correlation for benzo[a]pyrene mutagenesis in the V-79 hamster cell assay with 8-azaguanine as a marker when the cell lines with the highest (IAR-20) and lowest (IAR-27) metabolic competence were used as activating cell layers

  17. Enhanced oxidation of benzo[a]pyrene by crude enzyme extracts produced during interspecific fungal interaction of Trametes versicolor and Phanerochaete chrysosporium

    Institute of Scientific and Technical Information of China (English)

    Linbo Qian; Baoliang Chen

    2012-01-01

    The effects of interspecific fungal interactions between Trametes versicolor and Phanerochaete chrysosporium on laccase activity and enzymatic oxidation of polycyclic aromatic hydrocarbons (PAHs) were investigated.A deadlock between the two mycelia rather than replacement of one fungus by another was observed on an agar medium.The laccase activity in crude enzyme extracts from interaction zones reached a maximum after a 5-day incubation,which was significantly higher than that from regions of T.versicolor or P.chrysosporium alone.The enhanced induction of laccase activity lasted longer in half nutrition than in normal nutrition.A higher potential to oxidize benzo[a]pyrene by a crude enzyme preparation extracted from the interaction zones was demonstrated.After a 48 hr incubation period,the oxidation of benzo[a]pyrene by crude enzyme extracts from interaction zones reached 26.2%,while only 9.5% of benzo[a]pyrene was oxidized by crude extracts from T.versicolor.The oxidation was promoted by the co-oxidant 2,2'-azinobis-3-ethylbenzthiazoline-6-sulphonate diammonium salt (ABTS).These findings indicate that the application of co-culturing of white-rot fungi in bioremediation is a potential ameliorating technique for the restoration of PAH-contaminated soil.

  18. An investigation of endocrine disrupting effects and toxic mechanisms modulated by benzo[a]pyrene in female scallop Chlamys farreri

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Shuangmei; Pan, Luqing, E-mail: panlq@ouc.edu.cn; Sun, Xiaohua

    2013-11-15

    Highlights: •B[a]P disturbed progesterone, 17β-estradiol and testosterone production in scallop. •B[a]P inhibited 3β-HSD, CYP17 and 17β-HSD expression after a 10-day exposure. •B[a]P of lower dose elevated AHR-CYP1A expression but high dose B[a]P inhibited them. •ER and vitellogenin transcription was consistent with AHR after B[a]P exposure. •B[a]P exposure induced relatively developmental delay and impairment of ovary. -- Abstract: The purpose of this study was to investigate the endocrine disrupting effects induced by benzo[a]pyrene (B[a]P) and explore the underlying mechanisms in mollusks. In this study, sexually mature female Chlamys farreri were exposed to benzo[a]pyrene for 10 days at four different concentrations as 0, 0.025, 0.5 and 10 μg/L. Sex steroids were identified and quantified by electrochemiluminescence immunoassay (ECLIA) method and results showed that exposure to B[a]P exerts great suppression on 17β-estradiol, testosterone production and disrupts progesterone levels in ovary. Transcription of genes were detected and measured by real-time RT-PCR. It showed that at day 10 B[a]P inhibited 3β-HSD, CYP17 and 17β-HSD mRNA expression in a dose-dependent manner, which suggests that they could be potential targets of B[a]P that disrupt steroidogenic machinery. Moreover, 0.025 μg/L B[a]P activated transcription of aryl hydrocarbon receptor (AHR), AHR nuclear translocator (ARNT), CYP1A1 and estrogen receptor (ER), while 10 μg/L B[a]P suppressed all of them. The consistency of their responses to B[a]P exposure implies that AHR action may be involved in invertebrate CYP regulation and ER transcription despite of unknown mechanisms. Additionally, B[a]P exposure could induce ovarian impairment and developmental delay in C. farreri. Overall, sensitivity of C. farreri to endocrine disruption and toxicity suggests that C. farreri is a suitable species for study of endocrine-disrupting effects in marine invertebrates. This study will form a

  19. Investigation on the Protective Effects of Cranberry Against the DNA Damage Induced by Benzo[a]pyrene

    Directory of Open Access Journals (Sweden)

    José A. Morales-González

    2012-04-01

    Full Text Available There are few reports that demonstrate the antigenotoxic potential of cranberries. Although the types of berry fruits consumed worldwide are many, this paper focuses on cranberries that are commonly consumed in Mexico (Vaccinium macrocarpon species. The purpose of the present study is to determine whether cranberry ethanolic extract (CEE can prevent the DNA damage produced by benzo[a]pyrene (B[a]P using an in vivo mouse peripheral blood micronucleus assay. The experimental groups were organized as follows: a negative control group (without treatment, a positive group treated with B[a]P (200 mg/kg, a group administered with 800 mg/kg of CEE, and three groups treated with B[a]P and CEE (200, 400, and 800 mg/kg respectively. The CEE and benzo[a]pyrene were administered orally for a week, on a daily basis. During this period the body weight, the feed intake, and the determination of antigenotoxic potential were quantified. At the end of this period, we continued with the same determinations for one week more (recovery period but anymore administration of the substances. The animals treated with B[a]P showed a weight increase after the first week of administration. The same phenomenon was observed in the lots combined with B[a]P and CEE (low and medium doses. The dose of 800 mg/kg of CEE showed similar values to the control group at the end of the treatment period. In the second part of the assay, when the substances were not administered, these experimental groups regained their normal weight. The dose of CEE (800 mg/kg was not genotoxic nor cytotoxic. On the contrary, the B[a]P increases the frequency of micronucleated normochromatic erythrocytes (MNNE and reduces the rate of polychromatic erythrocytes (PE at the end of the treatment period. With respect to the combined lots, a significant decrease in the MN rate was observed from the sixth to the eighth day of treatment with the two high doses applied; the highest protection (60% was obtained with

  20. Preparation and surface active properties of oxypropylated α-hydroxyacids, α-hydroxyesters and α-, β-alkane diols

    Directory of Open Access Journals (Sweden)

    Shaker, N. O.

    1994-10-01

    Full Text Available A series of a-hydroxyacids RCH(OHCO2H, α-hydroxyesters RCH(OHCO2CH3 and α, β-alkane diols was synthetized and condensed with 5-20 moles propylene oxide to obtain nonionic surfactants. Some of the physicochemical properties and the biodegradability of these products were examined. The results showed that the best wetting properties were obtained by the addition of 15 oxypropylene groups to methyl α-hydroxymyristate. The α-hydroxymyristic acid with 20 moles of propylene oxide gave the highest foam. Biodegradation studies indicated that increasing both the chain length of the hydrophobic alkyl chain or the number of oxypropylene groups in the adduct decreased biodegradation.

    Una serie de α-hidroxiácidos RCH(OHCO2H, α-hidroxiésteres RCH(OHCO2CH3 y α, β-alcanodioles se sintetizaron y condensaron con 5-20 moles de óxido de propileno para obtener tensioactivos no iónicos. Se examinaron algunas propiedades fisicoquímicas y de biodegradabilidad de estos productos. Los resultados mostraron que las mejores propiedades humectantes se obtuvieron por adición de 15 grupos oxipropilenos a α-hidroximiristato de metilo.
    El ácido α-hidroximirístico con 20 moles de óxido de propileno dio la espuma más poderosa. Estudios de biodegradación indicaron que tanto el aumento de la longitud de cadena de los grupos alquilo hidrofóbicos como el número de grupos oxipropilenos en el aducto disminuyeron la biodegradación.

  1. CHARACTERIZATION AND FUNCTIONAL STUDY OF A PUTATIVE JUVENILE HORMONE DIOL KINASE IN THE COLORADO POTATO BEETLE Leptinotarsa decemlineata (Say).

    Science.gov (United States)

    Fu, Kai-Yun; Lü, Feng-Gong; Guo, Wen-Chao; Li, Guo-Qing

    2015-11-01

    Juvenile hormone diol kinase (JHDK) is an enzyme involved in JH degradation. In the present article, a putative JHDK cDNA (LdJHDK) was cloned from the Colorado potato beetle Leptinotarsa decemlineata. The cDNA consists of 814 bp, containing a 555 bp open reading frame encoding a 184 amino acid protein. LdJHDK reveals a high degree of identity to the previously reported insect JHDKs. It possesses three conserved purine nucleotide-binding elements, and contains three EF-hand motifs (helix-loop-helix structural domains). LdJHDK mRNA was mainly detected in hindgut and Malpighian tubules. Besides, a trace amount of LdJHDK mRNA was also found in thoracic muscles, brain-corpora cardiaca-corpora allata complex, foregut, midgut, ventral ganglia, fat body, epidermis, and hemocytes. Moreover, LdJHDK was expressed throughout all developmental stages. Within the first, second, and third larval instar, the expression levels of LdJHDK were higher just before and right after the molt, and were lower in the intermediate instar. In the fourth larval instar, the highest peak of LdJHDK occurred 56 h after ecdysis. Ingestion of double-stranded RNA (dsRNA) against LdJHDK successfully knocked down the target gene, increased JH titer, and significantly upregulated LdKr-h1 mRNA level. Knockdown of LdJHDK significantly impaired adult emergence. Thus, we provide a line of experimental evidence in L. decemlineata to support that LdJHDK encodes function protein involved in JH degradation. PMID:26280246

  2. Two-step biocatalytic route to biobased functional polyesters from omega-carboxy fatty acids and diols.

    Science.gov (United States)

    Yang, Yixin; Lu, Wenhua; Zhang, Xiaoyan; Xie, Wenchun; Cai, Minmin; Gross, Richard A

    2010-01-11

    Biobased omega-carboxy fatty acid monomers 1,18-cis-9-octadecenedioic, 1,22-cis-9-docosenedioic, and 1,18-cis-9,10-epoxy-octadecanedioic acids were synthesized in high conversion yields from oleic, erucic and epoxy stearic acids by whole-cell biotransformations catalyzed by C. tropicalis ATCC20962. Maximum volumetric yields in shake-flasks were 17.3, 14.2, and 19.1 g/L after 48 h conversion for oleic acid and 72 h conversions for erucic and epoxy stearic acids, respectively. Studies in fermentor with better control of pH and glucose feeding revealed that conversion of oleic acid to 1,18-cis-9-octadecenedioic acid by C. tropicalis ATCC20962 occurred with productivities up to 0.5 g/L/h. The conversion of omega-carboxy fatty acid monomers to polyesters was then studied using immobilized Candida antarctica Lipase B (N435) as catalyst. Polycondensations with diols were performed in bulk as well as in diphenyl ether. The retension of functionality from fatty acid, to omega-carboxy fatty acid monomer and to corresponding polyesters resulted in polymers with with unsaturated and epoxidized repeat units and M(w) values ranging from 25000 to 57000 g/mol. These functional groups along chains disrupted crystallization giving materials that are low melting (23-40 degrees C). In contrast, saturated polyesters prepared from 1,18-octadecanedioic acid and 1,8-octanediol have correspondingly higher melting transitions (88 degrees C). TGA results indicated that all synthesized polyesters showed high thermal stabilities. Thus, the preparation of functional monomers from C. tropicalis omega-oxidation of fatty acids provides a wide range of new monomer building blocks to construct functional polymers. PMID:20000460

  3. Punicalagin and Ellagic Acid Demonstrate Antimutagenic Activity and Inhibition of Benzo[a]pyrene Induced DNA Adducts

    Directory of Open Access Journals (Sweden)

    Maryam Zahin

    2014-01-01

    Full Text Available Punicalagin (PC is an ellagitannin found in the fruit peel of Punica granatum. We have demonstrated antioxidant and antigenotoxic properties of Punica granatum and showed that PC and ellagic acid (EA are its major constituents. In this study, we demonstrate the antimutagenic potential, inhibition of BP-induced DNA damage, and antiproliferative activity of PC and EA. Incubation of BP with rat liver microsomes, appropriate cofactors, and DNA in the presence of vehicle or PC and EA showed significant inhibition of the resultant DNA adducts, with essentially complete inhibition (97% at 40 μM by PC and 77% inhibition by EA. Antimutagenicity was tested by Ames test. PC and EA dose-dependently and markedly antagonized the effect of tested mutagens, sodium azide, methyl methanesulfonate, benzo[a]pyrene, and 2-aminoflourine, with maximum inhibition of mutagenicity up to 90 percent. Almost all the doses tested (50–500 μM exhibited significant antimutagenicity. A profound antiproliferative effect on human lung cancer cells was also shown with PC and EA. Together, our data show that PC and EA are pomegranate bioactives responsible for inhibition of BP-induced DNA adducts and strong antimutagenic, antiproliferative activities. However, these compounds are to be evaluated in suitable animal model to assess their therapeutic efficacy against cancer.

  4. Modulatory effects of catechin hydrate against genotoxicity, oxidative stress, inflammation and apoptosis induced by benzo(a)pyrene in mice.

    Science.gov (United States)

    Shahid, Ayaz; Ali, Rashid; Ali, Nemat; Hasan, Syed Kazim; Bernwal, Preeti; Afzal, Shekh Mohammad; Vafa, Abul; Sultana, Sarwat

    2016-06-01

    Benzo(a)pyrene [B(a)P], a polycyclic aromatic hydrocarbon (PAH) is a strong mutagen and potent carcinogen. The aim of the present study was to investigate the efficacy of catechin hydrate against B(a)P induced genotoxicity, oxidative stress, inflammation, apoptosis and to explore its underlying molecular mechanisms in the lungs of Swiss albino mice. Administration of B(a)P (125 mg/kg b. wt., p. o.) increased the activities of toxicity markers such as LPO, LDH and B(a)P metabolizing enzymes [NADPH-cytochrome P450 reductase (CYPOR) and microsomal epoxide hydrolase (mEH)] with subsequent decrease in the activities of tissue anti-oxidant armory (SOD, CAT, GPx, GR, GST, QR and GSH). It also caused DNA damage and activation of apoptotic and inflammatory pathway by upregulation of TNF-α, IL-6, NF-kB, COX-2, p53, bax, caspase-3 and down regulating Bcl-2. However, pre-treatment with catechin at a dose of 20 and 40 mg/kg significantly decreased LDH, LPO, B(a)P metabolizing enzymes and increased anti-oxidant armory as well as regulated apoptosis and inflammation in lungs. Histological results also supported the protective effects of catechin. The findings of the present studies suggested that catechin as an effective natural product attenuates B(a)P induced lung toxicity. PMID:27020533

  5. Effects of benzo(a)pyrene on the skeletal development of Sebastiscus marmoratus embryos and the molecular mechanism involved

    International Nuclear Information System (INIS)

    Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants, which have been known to be carcinogenic and teratogenic. However, the skeletal development toxicity of PAHs and the mechanism involved remain unclear. In fishes, the neurocranial and craniofacial skeleton develop as cartilage. The signaling molecules of hedgehog (Hh) family play crucial roles in regulating skeletal development. In the present study, rockfish (Sebastiscus marmoratus) embryos were exposed to benzo(a)pyrene (BaP) for 7 days at environmental levels (0.05, 0.5 and 5 nmol/L) which resulted in craniofacial skeleton deformities. BaP exposure reduced the cell proliferation activity in the craniofacial skeleton as detected by quantitative PCR and in situ hybridization. The expression of Sonic hedgehog (Shh), rather than Indian hedgehog (Ihh), was down-regulated in the craniofacial skeleton in the 0.5 and 5 nmol/L groups. Consistent with the Shh results, the expression of Ptch1 and Gli2 was decreased by BaP exposure and BMP4 was presented on changes in the 0.5 and 5 nmol/L groups. These results suggested that BaP could impair the expression and function of Shh signaling pathway, perturbing the proliferation of chondrocytes and so disturbing craniofacial skeletal development.

  6. Synergism of aromatic amines and benzo[a]pyrene in induction of Ah receptor-dependent genes.

    Science.gov (United States)

    Borza, Alexandra; Plöttner, Sabine; Wolf, Alexander; Behm, Claudia; Selinski, Silvia; Hengstler, Jan G; Roos, Peter H; Bolt, Hermann M; Kuhlmann, Jürgen; Föllmann, Wolfram

    2008-12-01

    Aromatic amines have been shown to cause bladder cancer. However, epithelial cells of the urinary bladder, cells of origin of bladder cancer, may be exposed to numerous substances besides aromatic amines. In the present study, we analysed possible interactions between the aromatic amines 4-aminobiphenyl (4-ABP) as well as 2-naphthylamine (2-NA) and the polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P). For this purpose we incubated primary porcine urinary bladder epithelial cells (PUBEC) with concentrations of 1 to 50 microM 4-ABP with and without co-exposure to B[a]P. As expected B[a]P increased mRNA expression of cytochrome P450 1A1 (CYP1A1), whereas 4-ABP had no effect. However, when co-exposed 4-ABP enhanced the induction of CYP1A1 by B[a]P. This result was confirmed by Western blot analysis of CYP1A1 protein expression. A similar effect as for CYP1A1 was also observed for cyclooxygenase-2 (COX-2) and UDP-glucuronosyltransferase 1 (UGT1). Next, we studied co-exposures of 2-NA and B[a]P. Similar as for 4-ABP also 2-NA enhanced B[a]P-mediated induction of CYP1A1. Our results demonstrate that some aromatic amines may enhance the influence of B[a]P on Ah receptor-dependent genes. PMID:18989657

  7. Tissue-specific antioxidant responses in pale chub (Zacco platypus) exposed to copper and benzo[a]pyrene.

    Science.gov (United States)

    Kim, Woo-Keun; Park, June-Woo; Lim, Eun-Suk; Lee, Sung-Kyu; Kim, Jungkon; Kim, Sunmi; Lee, Sang-Woo; Choi, Kyungho; Jung, Jinho

    2014-05-01

    In this study, antioxidant responses including lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST), were evaluated in the liver, gill and muscle tissues of pale chub (Zacco platypus) exposed to copper (Cu) and benzo[a]pyrene (BaP). Cu exposure induced significant antioxidant responses in Z. platypus, particularly in the liver, whereas BaP exposure had a negligible effect. Following Cu exposure, both SOD and CAT activity increased in a concentration-dependent manner, showing significant correlations with malondialdehyde (MDA) levels as a measure of LPO (r = 0.646 and 0.663, respectively). SOD, CAT and GST mRNA levels were also enhanced following Cu exposure, except at 20 μg L(-1), although significant correlations with antioxidant enzyme activities were not found. The results of this study suggest that combined information on SOD and CAT activities together with LPO levels in the liver could be a useful indicator for assessing oxidative stress in freshwater fish. PMID:24477393

  8. Effects of benzo(a)pyrene on the skeletal development of Sebastiscus marmoratus embryos and the molecular mechanism involved

    Energy Technology Data Exchange (ETDEWEB)

    He Chengyong [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); Zuo Zhenghong [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen (China); Shi Xiao; Li Ruixia; Chen Donglei; Huang Xin; Chen Yixin [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); Wang Chonggang, E-mail: cgwang@xmu.edu.cn [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen (China)

    2011-01-25

    Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants, which have been known to be carcinogenic and teratogenic. However, the skeletal development toxicity of PAHs and the mechanism involved remain unclear. In fishes, the neurocranial and craniofacial skeleton develop as cartilage. The signaling molecules of hedgehog (Hh) family play crucial roles in regulating skeletal development. In the present study, rockfish (Sebastiscus marmoratus) embryos were exposed to benzo(a)pyrene (BaP) for 7 days at environmental levels (0.05, 0.5 and 5 nmol/L) which resulted in craniofacial skeleton deformities. BaP exposure reduced the cell proliferation activity in the craniofacial skeleton as detected by quantitative PCR and in situ hybridization. The expression of Sonic hedgehog (Shh), rather than Indian hedgehog (Ihh), was down-regulated in the craniofacial skeleton in the 0.5 and 5 nmol/L groups. Consistent with the Shh results, the expression of Ptch1 and Gli2 was decreased by BaP exposure and BMP4 was presented on changes in the 0.5 and 5 nmol/L groups. These results suggested that BaP could impair the expression and function of Shh signaling pathway, perturbing the proliferation of chondrocytes and so disturbing craniofacial skeletal development.

  9. Protective effect of curcumin and chlorophyllin against DNA mutation induced by cyclophosphamide or benzo[a]pyrene

    Energy Technology Data Exchange (ETDEWEB)

    Ibrahim, M.A.; Elbehairy, A.M.; Ghoneim, M.A.; Amer, H.A. [Cairo Univ., Giza (Egypt). Biochemistry Dept. and Biotechnology Center

    2007-03-15

    The current study was carried out to evaluate the potency of curcumin and chlorophyllin as natural antioxidants to reduce the oxidative stress markers induced by cyclophosphamide (CP) and benzo[a]pyrene [B(a)P] which were used as free radical inducers. For this purpose, 126 male albino rats were used. The animals were assigned into 4 main groups: negative control group; oxidant-treated group (subdivided into two subgroups: cyclophosphamide- treated group and benzo[a]pyrene-treated group); curcumin-treated group; and chlorophyllin-treated group. Liver samples were collected after two days post the oxidant inoculation and at the end of the experimental period (10 weeks). These samples were examined for determination of liver microsomal malondialdehyde (MDA), DNA fragmentation, restriction fragment length polymorphism (RFLP) and 8-hydroxy deoxyguanosine (8-OHdG) concentration. Both CP and B(a)P caused increments in DNA fragmentation percentages, liver microsomal MDA, concentration of 8-OHdG and induced point mutation. Treatment of rats with either curcumin or chlorophyllin revealed lower DNA fragmentation percentages, liver microsomal MDA concentration, concentration of 8-OHdG and prevented induction of mutations, i. e., reversed the oxidative stress induced by CP and B(a)P and proved that they were capable of protecting rats against the oxidative damage evoked by these oxidants. (orig.)

  10. Can we use modelling methodologies to assess airborne benzo[a]pyrene from biomonitors? A comprehensive evaluation approach

    Directory of Open Access Journals (Sweden)

    N. Ratola

    2015-09-01

    Full Text Available Biomonitoring data available on levels of atmospheric polycyclic aromatic hydrocarbons (PAHs in pine needles from the Iberian Peninsula was used to estimate air concentrations of benzo[a]pyrene (BaP and, at the same time, fuelled the comparison with chemistry transport model representations. Simulations with the modelling system WRF + CHIMERE were validated against data from the European Monitoring and Evaluation Programme (EMEP air sampling network and using modelled atmospheric concentrations as a consistent reference in order to compare the performance of vegetation-to-air estimating methods. A spatial and temporal resolution of 9 km and 1 h was implemented. The field-based database relied on a pine needles sampling scheme comprising 33 sites in Portugal and 37 sites in Spain complemented with the BaP measurements available from the EMEP sites. The ability of pine needles to act as biomonitoring markers for the atmospheric concentrations of BaP was estimated converting the levels obtained in pine needles into air concentrations by six different approaches, one of them presenting realistic concentrations when compared to the modelled atmospheric values. The justification for this study is the gaps still existing in the knowledge of the life cycles of semi-volatile organic compounds (SVOCs, particularly the partition processes between air and vegetation. The strategy followed in this work allows the definition of the transport patterns (e.g. dispersion established by the model for atmospheric concentrations and the estimated values in vegetation.

  11. Coassimilation of dietary fat and benzo(a)pyrene in the small intestine: an absorption model using the killifish

    Energy Technology Data Exchange (ETDEWEB)

    Vetter, R.D.; Carey, M.C.; Patton, J.S.

    1985-04-01

    Benzo(a)pyrene (BP) was dissolved in dietary fat and fed in a single dose to killifish (Fundulus heteroclitus). Fluorescence microscopic examinations of small intestinal content and frozen sections of whole small intestine revealed that during fat digestion BP was codispersed in liquid crystalline product phases produced during lipolysis and then coabsorbed with dietary lipid followed by its reappearance in intracellular fat droplets. During the time that the absorbed fat remained in the enterocytes, BP fluorescence was initially concentrated in the intracellular fat droplets and then spread throughout the cytosol of the enterocytes. Tissue analyses showed that BP was rapidly metabolized in the intestine and transported to the gallbladder. These studies show that separation of a dissolved hydrophobic carcinogen from dietary fat occurs primarily after the fat has been digested, dispersed, absorbed, and reassembled in the enterocyte. The inability of the enterocyte to discriminate between dietary fat and dissolved carcinogenic compounds may be a partial explanation of the observed link between high fat diets and the incidence of some cancers. In vertebrates, the intestine and not the liver, appears to be the major site of metabolism of dietary polycyclic aromatic hydrocarbons (PAHs).

  12. Enhancement of the genotoxicity of benzo[a]pyrene by arecoline through suppression of DNA repair in HEp-2 cells.

    Science.gov (United States)

    Huang, J L; Lu, H H; Lu, Y N; Hung, P S; Lin, Y J; Lin, C C; Yang, C C; Wong, T Y; Lu, S Y; Lin, C S

    2016-06-01

    The International Agency for Research on Cancer lists the principal component of betel quid (BQ), the areca nut, and that of cigarette smoke, benzo[a]pyrene (BaP), as Group 1 carcinogens. Epidemiological studies have shown that coexposure of BQ and cigarette smoke markedly increases the risk of cancer. We previously demonstrated that arecoline, the most abundant alkaloid in the areca nut, inhibits nucleotide excision repair through the repression of p53 activity. To investigate the combined potency of arecoline and BaP in carcinogenesis, we treated human epithelial HEp-2 cells with subcytotoxic doses of arecoline and BaP, alone or in combination, and examined the effects on DNA damage and repair. When exposed for 24h, BaP enhanced DNA repair and p53 transactivation activity. However, these enhancements were suppressed through concurrent treatment of the cells with arecoline. Using a Comet assay, we found that extended exposure to arecoline and BaP caused moderate-to-severe DNA damage in 60% of the cells. Expression of the XPD helicase was transcriptionally suppressed by 1week of treatment with BaP. Our studies have revealed potential targets in the DNA repair pathway that are affected by BQ and tobacco components, as well as the effect of these components on carcinogenesis. PMID:26891812

  13. Can we use modelling methodologies to assess airborne benzo[a]pyrene from biomonitors? A comprehensive evaluation approach

    Science.gov (United States)

    Ratola, N.; Jiménez-Guerrero, P.

    2015-09-01

    Biomonitoring data available on levels of atmospheric polycyclic aromatic hydrocarbons (PAHs) in pine needles from the Iberian Peninsula was used to estimate air concentrations of benzo[a]pyrene (BaP) and, at the same time, fuelled the comparison with chemistry transport model representations. Simulations with the modelling system WRF + CHIMERE were validated against data from the European Monitoring and Evaluation Programme (EMEP) air sampling network and using modelled atmospheric concentrations as a consistent reference in order to compare the performance of vegetation-to-air estimating methods. A spatial and temporal resolution of 9 km and 1 h was implemented. The field-based database relied on a pine needles sampling scheme comprising 33 sites in Portugal and 37 sites in Spain complemented with the BaP measurements available from the EMEP sites. The ability of pine needles to act as biomonitoring markers for the atmospheric concentrations of BaP was estimated converting the levels obtained in pine needles into air concentrations by six different approaches, one of them presenting realistic concentrations when compared to the modelled atmospheric values. The justification for this study is the gaps still existing in the knowledge of the life cycles of semi-volatile organic compounds (SVOCs), particularly the partition processes between air and vegetation. The strategy followed in this work allows the definition of the transport patterns (e.g. dispersion) established by the model for atmospheric concentrations and the estimated values in vegetation.

  14. Metabolic and immune impairments induced by the endocrine disruptors benzo[a]pyrene and triclosan in Xenopus tropicalis.

    Science.gov (United States)

    Regnault, Christophe; Willison, John; Veyrenc, Sylvie; Airieau, Antinéa; Méresse, Patrick; Fortier, Marlène; Fournier, Michel; Brousseau, Pauline; Raveton, Muriel; Reynaud, Stéphane

    2016-07-01

    Despite numerous studies suggesting that amphibians are highly sensitive to cumulative anthropogenic stresses, the role played by endocrine disruptors (EDs) in the decline of amphibian populations remains unclear. EDs have been extensively studied in adult amphibians for their capacity to disturb reproduction by interfering with the sexual hormone axis. Here, we studied the in vivo responses of Xenopus tropicalis males exposed to environmentally relevant concentrations of each ED, benzo[a]pyrene (BaP) and triclosan (TCS) alone (10 μg L(-1)) or a mixture of the two (10 μg L(-1) each) over a 24 h exposure period by following the modulation of the transcription of key genes involved in metabolic, sexual and immunity processes and the cellular changes in liver, spleen and testis. BaP, TCS and the mixture of the two all induced a marked metabolic disorder in the liver highlighted by insulin resistance-like and non-alcoholic fatty liver disease (NAFLD)-like phenotypes together with hepatotoxicity due to the impairment of lipid metabolism. For TCS and the mixture, these metabolic disorders were concomitant with modulation of innate immunity. These results confirmed that in addition to the reproductive effects induced by EDs in amphibians, metabolic disorders and immune system disruption should also be considered. PMID:27153234

  15. Quantitative determination of benzo[a]pyrene in foodstuffs using benzo[a]pyrene[G-3H

    International Nuclear Information System (INIS)

    A method for quantitative determination of nano gram level of benzo(a)pyrene (BP) in foodstuffs using tritiated BP(3H-BP) was described. Extracts from foodstuffs, having been added a certain amount of 3H-BP, were fractionated by column chromatography on Florisil, and thinlayer chromatography on acetylated cellulose. Concentration and radio activity of BP in the final fraction were determined by fluorescence spectrometry and liquid scintillation. Recovery ratio of each experiment was obtained by comparing the radio activities of added 3H-BP and separated BP. Concentration of BP in the sample analyzed was calculated from the amount of isolated BP and the recovery ratio in each experiment. A quantitative limit of BP by this method was 0.2 ppb when 50 g of sample was used. By this method, contents of BO in each sample of Tenpura oil, salad oil, flour, and polished rice were determined as 0.6, 0.2, 0.1 and < 0.1 ppb on average, respectively. (auth.)

  16. Transcriptional profiling of the mouse hippocampus supports an NMDAR‐mediated neurotoxic mode of action for benzo[a]pyrene

    Science.gov (United States)

    Chepelev, Nikolai L.; Long, Alexandra S.; Bowers, Wayne J.; Gagné, Rémi; Williams, Andrew; Kuo, Byron; Phillips, David H.; Arlt, Volker M.; White, Paul A.

    2016-01-01

    Benzo[a]pyrene (BaP) is a genotoxic carcinogen and a neurotoxicant. The neurotoxicity of BaP is proposed to arise from either genotoxicity leading to neuronal cell death, or perturbed expression of N‐methyl‐d‐aspartate receptor (NMDAR) subunits. To explore these hypotheses, we profiled hippocampal gene expression of adult male Muta™Mouse administered 0, 1, 35, or 70 mg BaP/kg bw per day by oral gavage for 3 days. Transcriptional profiles were examined by RNA‐sequencing (RNA‐seq), DNA microarrays, and real‐time quantitative reverse transcription polymerase chain reaction (RT‐PCR). BaP‐DNA adducts in the cerebellum were quantified by 32P‐post‐labeling to measure genotoxicity. RNA‐seq revealed altered expression of 0, 260, and 219 genes (P‐value Environ. Mol. Mutagen. 57:350–363, 2016. © 2016 Her Majesty the Queen in Right of Canada. Environmental and Molecular Mutagenesis © 2016 Environmental Mutagen Society. PMID:27195522

  17. Proteomic and metabolomic analysis on the toxicological effects of Benzo[a]pyrene in pearl oyster Pinctada martensii.

    Science.gov (United States)

    Chen, Hao; Song, Qinqin; Diao, Xiaoping; Zhou, Hailong

    2016-06-01

    Benzo[a]pyrene (BaP) is one of the typical toxic polycyclic aromatic hydrocarbons (PAHs) that are widely present in marine environment. BaP has diverse toxic effects, including teratogenic, carcinogenic, mutagenic effects and so on, in various organisms. In this work, we focused on the differential proteomic and metabolomic responses in the digestive gland of pearl oyster Pinctada martensii exposed to two doses of BaP (1 and 10μg/L). Metabolic responses revealed that the high dose of BaP (10μg/L) mainly caused disturbances in osmotic regulation and energy metabolism in the digestive gland. Proteomic responses indicated that both doses of BaP induced disturbances in energy metabolism, cytoskeleton, cell injury, oxidative stress and signal transduction based on the differential proteomic biomarkers. Overall, these results demonstrated a number of potential biomarkers that were characterized by an integrated proteomic and metabolomic approach and provided a useful insight into the toxicological effects on pearl oyster P. martensii. PMID:26999675

  18. Stabilization of membrane bound ATPases and lipid peroxidation by carotenoids from Chlorococcum humicola in Benzo(a)pyrene induced toxicity

    Institute of Scientific and Technical Information of China (English)

    Bhagavathy S; Sumathi P

    2012-01-01

    Objective: To identify the alteration of the membrane potential and the effect of carotenoid extracts from Chlorococcum humicola (C. humicola) on membrane bound ATPases and lipid peroxidation. Methods: The total carotenoids were extracted from C. humicola. Four groups of Swiss albino mice were treated as control, Benzo(a)pyrene [B(a)P], total carotenoids, B(a)P +total carotenoids respectively for a period of 60 days. Membrane lipid peroxidation and ATPases (Total ATPases, Ca2+- ATPases, Mg2+ - ATPases, Na+K+ - ATPase) were determined in lung, liver and erythrocyte samples. Results: The activity of total ATPase was found to be significantly increased in the B(a)P treated liver and lung tissue. Erythrocyte membrane also showed higher ATPase activity which was significantly reverted on total carotenoid treatment. Conclusions:It can be concluded that the changes in membrane potential favour the functional deterioration of physiological system. The overall findings demonstrates that the animals post treated with carotenoid extract from C. humicola may maintains the alterations in membrane bound ATPase and lipid peroxidation in tissues against the carcinogenic chemical and hence aid in establishing the membrane potential action. Therefore C. humicola can be further extended to exploits its possible application for various health benefits as neutraceuticals and food additives.

  19. Small angle neutron scattering study on the aggregation behaviour of PEO–PPO–PEO copolymers in the presence of a hydrophobic diol

    Indian Academy of Sciences (India)

    B Bharatiya; V K Aswal; P Bahadur

    2008-11-01

    Small angle neutron scattering (SANS) measurements on aqueous solutions of four polyethylene oxide–polypropylene oxide–polyethylene oxide block copolymers (commercially known as Pluronic®)F88, P85, F127 and P123 in the presence of hydrophobic C14Diol (also known as Surfynol® 104) reveal information on micellization, micellar size and micellar transitions. While most hydrophilic F88 (with least PPO/PEO ratio) remained unimers in water at 30◦ C, other copolymers formed micellar solutions. Surfynol® 104 is sparingly soluble in water to only about ∼ 0.1 wt%, but on addition to pluronic solution, it gets incorporated in the micellar region of block copolymer which leads to increase in aggregation number and transformation of spherical to ellipsoidal micelles. The added diol-induced micellization in F88, though hydrophilic copolymers F88 and F127 did not show any appreciable micellar growth or shape changes as observed for P85 and P123 (which are comparatively more hydrophobic). The SANS results on copolymer pairs with same molecular weight PPO but different % PEO (viz. F88 and P85, F127 and P123) and with same molecular weight PEO but different PPO (F88 and F127) reveal that the copolymer with large PPO/PEO ratio facilitate micellar transition in the presence of diol. An increase in temperature and presence of added electrolyte (sodium chloride) in the solution further enhances these effects. The micellar parameters for these systems were found out using available software and are reported.

  20. Acaricidal effects of Corymbia citriodora oil containing para-menthane-3,8-diol against nymphs of Ixodes ricinus (Acari: Ixodidae)

    OpenAIRE

    Elmhalli, Fawzeia; Pålsson, Katinka; Örberg, Jan; Jaenson, Thomas

    2009-01-01

    The toxicity of para-menthane-3,8-diol (PMD), the main arthropod-repellent compound in the oil of the lemon eucalyptus, Corymbia citriodora, was evaluated against nymphs of Ixodes ricinus using five methods (A-E) of a contact toxicity bioassay. Mortality rates were estimated by recording numbers of dead nymphs at 30 min intervals during the first 5 h after the start of exposure and at longer intervals thereafter. The mortality rate increased with increasing concentration of PMD and duration o...

  1. 5-Cholesten-3β,25-Diol 3-Sulfate Decreases Lipid Accumulation in Diet-Induced Nonalcoholic Fatty Liver Disease Mouse Model

    OpenAIRE

    Xu, Leyuan; Kim, Jin Koung; Bai, Qianming; Zhang, Xin; Kakiyama, Genta; Min, Hae-Ki; Arun J Sanyal; Pandak, William M.; Ren, Shunlin

    2013-01-01

    Sterol regulatory element-binding protein-1c (SREBP-1c) increases lipogenesis at the transcriptional level, and its expression is upregulated by liver X receptor α (LXRα). The LXRα/SREBP-1c signaling may play a crucial role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We previously reported that a cholesterol metabolite, 5-cholesten-3β,25-diol 3-sulfate (25HC3S), inhibits the LXRα signaling and reduces lipogenesis by decreasing SREBP-1c expression in primary hepatocytes. T...

  2. Steviamine, a new class of indolizidine alkaloid [(1R,2S,3R,5R,8aR-3-hydroxymethyl-5-methyloctahydroindolizine-1,2-diol hydrobromide

    Directory of Open Access Journals (Sweden)

    Amber L. Thompson

    2009-11-01

    Full Text Available X-ray crystallographic analysis of the title hydrobromide salt, C10H20N+·Br−, of (1R,2S,3R,5R,8aR-3-hydroxymethyl-5-methyloctahydroindolizine-1,2-diol defines the absolute and relative stereochemistry at the five chiral centres in steviamine, a new class of polyhydroxylated indolizidine alkaloid isolated from Stevia rebaudiana (Asteraceae leaves. In the crystal structure, molecules are linked by intermolecular O—H...Br and N—H...Br hydrogen bonds, forming double chains around the twofold screw axes along the b-axis direction. Intramolecular O—H...O interactions occur.

  3. QSPR models based on molecular mechanics and quantum chemical calculations. 1. Construction of Boltzmann averaged descriptors for alkanes, alcohols, diols, ethers and cyclic compounds

    DEFF Research Database (Denmark)

    Dyekjær, Jane Dannow; Rasmussen, Kjeld; Jonsdottir, Svava Osk

    2002-01-01

    Values for nine descriptors for QSPR (quantitative structure-property relationships) modeling of physical properties of 96 alkanes, alcohols, ethers, diols, triols and cyclic alkanes and alcohols in conjunction with the program Codessa are presented. The descriptors are Boltzmann-averaged by...... selection of the most relevant conformers out of a set of possible molecular conformers generated by a systematic scheme presented in this paper. Six of these descriptors are calculated with molecular mechanics and three with quantum chemical methods. Especially interesting descriptors are the relative van...

  4. Biotransformation of (-)-α-pinene and geraniol to α-terpineol and p-menthane-3,8-diol by the white rot fungus, Polyporus brumalis.

    Science.gov (United States)

    Lee, Su-Yeon; Kim, Seon-Hong; Hong, Chang-Young; Park, Se-Yeong; Choi, In-Gyu

    2015-07-01

    In this study, the monoterpenes, α-pinene and geraniol, were biotransformed to synthesize monoterpene alcohol compounds. Polyporus brumalis which is classified as a white rot fungus was used as a biocatalyst. Consequently α-terpineol was synthesized from α-pinene by P. brumalis mycelium, after three days. Moreover, another substrate, the acyclic monoterpenoids geraniol was transformed into the cyclic compound, p-menthane-3, 8-diol (PMD). The main metabolites, i.e., α-terpineol and PMD, are known to be bioactive monoterpene alcohol compounds. This study highlights the potential of fungal biocatalysts for monoterpene transformation. PMID:26115995

  5. Synthesis and characterization of new polyesters based on 2,5-bis[(4-chloro carboxyanilino)carbonyl]pyridine and aromatic diols

    Institute of Scientific and Technical Information of China (English)

    Khalil; Faghihi

    2010-01-01

    Six new polyesters 7a-f were synthesized through the solution polycondensation reaction of diacid chloride 5 with six aromatic diols 6a-f in N,N-dimethyl acetamide(DMAc) as solvent in the presence of pyridine as base.The polycondensation reaction produced a series of novel polyester containing pyridyl moiety in the main chain in high yields with inherent viscosities between 0.35 and 0.54 dL/g.The resulted polymers were fully characterized by means of FT-IR spectroscopy,elemental analyses,inherent viscosi...

  6. Development of analytical methods for the gas chromatographic determination of 1,2-epoxy-3-butene, 1,2:3,4-diepoxybutane, 3-butene-1,2-diol, 3,4-epoxybutane-1,2-diol and crotonaldehyde from perfusate samples of 1,3-butadiene exposed isolated mouse and rat livers

    Energy Technology Data Exchange (ETDEWEB)

    Bhowmik, S.; Schuster, A.; Filser, J.G.

    2003-07-01

    Mutagenicity and carcinogenicity of 1,3-butadiene (BD) highly probably results from epoxide metabolites as 1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane (DEB) and 3,4-epoxybutane-1,2-diol (EBD). A further metabolite crotonaldehyde (CA) has also been discussed to be relevant. So far, in BD exposed rodents only EB and DEB concentrations had been quantified. However, the methods used were either not very sensitive or instrumentally expensive. Therefore, the goal of the present work was to establish simple analytical methods selective and sensitive enough to determine all of these compounds and a further secondary BD intermediate, 3-butene-1,2-diol (B-diol), in BD exposed rodent livers. The once-through perfused liver system was chosen for testing the applicability of the methods to be developed, since it enables BD exposures of this quantitatively most relevant metabolising organ near to the in-vivo situation. All the metabolites were extracted from the aqueous perfusion medium and analysed using a gas chromatograph equipped with a mass selective detector (GC/MS) in the PCI mode. (orig.)

  7. The androgen 5alpha-dihydrotestosterone and its metabolite 5alpha-androstan-3beta, 17beta-diol inhibit the hypothalamo-pituitary-adrenal response to stress by acting through estrogen receptor beta-expressing neurons in the hypothalamus.

    Science.gov (United States)

    Lund, Trent D; Hinds, Laura R; Handa, Robert J

    2006-02-01

    Estrogen receptor beta (ERbeta) and androgen receptor (AR) are found in high levels within populations of neurons in the hypothalamus. To determine whether AR or ERbeta plays a role in regulating hypothalamo-pituitary-adrenal (HPA) axis function by direct action on these neurons, we examined the effects of central implants of 17beta-estradiol (E2), 5alpha-dihydrotestosterone (DHT), the DHT metabolite 5alpha-androstan-3beta, 17beta-diol (3beta-diol), and several ER subtype-selective agonists on the corticosterone and adrenocorticotropin (ACTH) response to immobilization stress. In addition, activation of neurons in the paraventricular nucleus (PVN) was monitored by examining c-fos mRNA expression. Pellets containing these compounds were stereotaxically implanted near the PVN of gonadectomized male rats. Seven days later, animals were killed directly from their home cage (nonstressed) or were restrained for 30 min (stressed) before they were killed. Compared with controls, E2 and the ERalpha-selective agonists moxestrol and propyl-pyrazole-triol significantly increased the stress induced release of corticosterone and ACTH. In contrast, central administration of DHT, 3beta-diol, and the ERbeta-selective compound diarylpropionitrile significantly decreased the corticosterone and ACTH response to immobilization. Cotreatment with the ER antagonist tamoxifen completely blocked the effects of 3beta-diol and partially blocked the effect of DHT, whereas the AR antagonist flutamide had no effect. Moreover, DHT, 3beta-diol, and diarylpropionitrile treatment significantly decreased restraint-induced c-fos mRNA expression in the PVN. Together, these studies indicate that the inhibitory effects of DHT on HPA axis activity may be in part mediated via its conversion to 3beta-diol and subsequent binding to ERbeta. PMID:16452668

  8. Integrative assessment of biomarker responses in pale chub (Zacco platypus) exposed to copper and benzo[a]pyrene.

    Science.gov (United States)

    Kim, Woo-Keun; Lee, Sung-Kyu; Choi, Kyungho; Jung, Jinho

    2013-06-01

    Multi-level biomarker responses (molecular/biochemical and histological/physiological levels) were studied to assess the sublethal toxicities of copper (Cu: 1.25, 5, and 20μg/L) and benzo[a]pyrene (BaP: 0.5, 5, and 50μg/L) induced in the freshwater pale chub Zacco platypus. Except for the kidney tissues when exposed to 20μg Cu/L, no significant differences were observed at the histological or physiological levels among the treatment groups. However, various molecular and biochemical responses were observed in Z. platypus, and these responses primarily depended on exposure time. Upon Cu exposure, both DNA single-strand breaks (COMET) and metallothionein (MT) concentration significantly increased after 4 days, whereas there were no significant changes after 14 days of exposure. Both 4 and 14 days of BaP exposure induced significant increases in COMET and 7-ethoxyresorufin-O-deethylase (EROD) activity, but there was no significant difference between them. Additionally, both Cu and BaP induced acetylcholinesterase (AChE) activity only after 14 days of exposure. The current findings demonstrate that the differences in the responses of MT and EROD are associated with each chemical's particular mode of action. Biomarker responses at the molecular and biochemical levels were quantized in terms of the integrated biomarker response (IBR) index to compare the toxicities of Cu and BaP. The IBR values were well correlated with the concentrations of Cu and BaP, and the correlations were enhanced at 4 days of exposure (r(2)=0.849 and 0.945, respectively) compared with 14 days (r(2)=0. 412 and 0.634, respectively). These results suggest that the IBR index may be a useful tool for the integrative quantification of the molecular and biochemical biomarker responses in a short-term exposure to Cu and BaP. PMID:23478165

  9. Toxicogenomic outcomes predictive of forestomach carcinogenesis following exposure to benzo(a)pyrene: Relevance to human cancer risk

    Energy Technology Data Exchange (ETDEWEB)

    Labib, Sarah, E-mail: Sarah.Labib@hc-sc.gc.ca; Guo, Charles H., E-mail: Charles.Guo@hc-sc.gc.ca; Williams, Andrew, E-mail: Andrew.Williams@hc-sc.gc.ca; Yauk, Carole L., E-mail: Carole.Yauk@hc-sc.gc.ca; White, Paul A., E-mail: Paul.White@hc-sc.gc.ca; Halappanavar, Sabina, E-mail: Sabina.Halappanavar@hc-sc.gc.ca

    2013-12-01

    Forestomach tumors are observed in mice exposed to environmental carcinogens. However, the relevance of this data to humans is controversial because humans lack a forestomach. We hypothesize that an understanding of early molecular changes after exposure to a carcinogen in the forestomach will provide mode-of-action information to evaluate the applicability of forestomach cancers to human cancer risk assessment. In the present study we exposed mice to benzo(a)pyrene (BaP), an environmental carcinogen commonly associated with tumors of the rodent forestomach. Toxicogenomic tools were used to profile gene expression response in the forestomach. Adult Muta™Mouse males were orally exposed to 25, 50, and 75 mg BaP/kg-body-weight/day for 28 consecutive days. The forestomach was collected three days post-exposure. DNA microarrays, real-time RT-qPCR arrays, and protein analyses were employed to characterize responses in the forestomach. Microarray results showed altered expression of 414 genes across all treatment groups (± 1.5 fold; false discovery rate adjusted P ≤ 0.05). Significant downregulation of genes associated with phase II xenobiotic metabolism and increased expression of genes implicated in antigen processing and presentation, immune response, chemotaxis, and keratinocyte differentiation were observed in treated groups in a dose-dependent manner. A systematic comparison of the differentially expressed genes in the forestomach from the present study to differentially expressed genes identified in human diseases including human gastrointestinal tract cancers using the NextBio Human Disease Atlas showed significant commonalities between the two models. Our results provide molecular evidence supporting the use of the mouse forestomach model to evaluate chemically-induced gastrointestinal carcinogenesis in humans. - Highlights: • Benzo(a)pyrene-mediated transcriptomic response in the forestomach was examined. • The immunoproteosome subunits and MHC class I

  10. Benzo[a]pyrene induces intercellular adhesion molecule-1 through a caveolae and aryl hydrocarbon receptor mediated pathway

    International Nuclear Information System (INIS)

    Toxicologic and epidemiologic studies have linked benzo[a]pyrene (B[a]P) exposure with cardiovascular diseases such as atherosclerosis. The mechanisms of action leading to these diseases have not been fully understood. One key step in the development of atherosclerosis is vascular endothelial dysfunction, which is characterized by increased adhesiveness. To determine if B[a]P could lead to increased endothelial adhesiveness, the effects of B[a]P on human endothelial cell intercellular adhesion molecule-1 (ICAM-1) expression was investigated. B[a]P was able to increase ICAM-1 protein only after pretreatment with the aryl hydrocarbon receptor (AhR) agonist β-naphthoflavone (β-NF). Knockdown of AhR by siRNA or treatment with AhR antagonist α-naphthoflavone (α-NF) eliminated the induction of ICAM-1 from B[a]P, confirming the necessity of AhR in this process. Likewise, B[a]P only increased monocyte adhesion to the vascular endothelium when cells were pretreated with β-NF. Experiments were done to define a signaling mechanism. B[a]P increased phosphorylation of MEK and p38-MAPK, and inhibitors to these proteins blunted the ICAM-1 induction. B[a]P was also able to increase AP-1 DNA binding and phosphorylation of cJun. Phosphorylation of cJun was disrupted by MEK and p38-MAPK inhibitors linking the signaling cascade. Finally, the importance of membrane microdomains, caveolae, was demonstrated by knockdown of the structural protein caveolin-1. Disruption of caveolae eliminated the B[a]P-induced ICAM-1 expression. These data suggest a possible pro-inflammatory mechanism of action of B[a]P involving caveolae, leading to increased vascular endothelial adhesiveness, and this inflammation may be a critical step in the development of B[a]P-induced atherosclerosis

  11. Chronic exposure to low benzo[a]pyrene level causes neurodegenerative disease-like syndromes in zebrafish (Danio rerio).

    Science.gov (United States)

    Gao, Dongxu; Wu, Meifang; Wang, Chonggang; Wang, Yuanchuan; Zuo, Zhenghong

    2015-10-01

    Previous epidemiological and animal studies report that exposure to environmental pollutant exposure links to neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Benzo[a]pyrene (BaP), a neurotoxic polycyclic aromatic hydrocarbon, has been increasingly released into the environment during recent decades. So far, the role of BaP on the development of neurodegenerative diseases remaind unclear. This study aimed to determine whether chronic exposure to low dose BaP would cause neurodegenerative disease-like syndromes in zebrafish (Danio rerio). We exposed zebrafish, from early embryogenesis to adults, to environmentally relevant concentrations of BaP for 230 days. Our results indicated that BaP decreased the brain weight to body weight ratio, locomotor activity and cognitive ability; induced the loss of dopaminergic neurons; and resulted in neurodegeneration. In addition, obvious cell apoptosis in the brain was found. Furthermore, the neurotransmitter levels of dopamine and 3,4-dihydroxyphenylacetic acid, the mRNA levels of the genes encoding dopamine transporter, Parkinson protein 7, phosphatase and tensin-induced putative kinase 1, ubiquitin carboxy-terminal hydrolase L1, leucine-rich repeat serine/threonine kinase 2, amyloid precursor protein b, presenilin 1 and presenilin 2 were significantly down-regulated by BaP exposure. These findings suggest that chronic exposure to low dose BaP could cause the behavioral, neuropathological, neurochemical, and genetic features of neurodegenerative diseases. This study provides clues that BaP may constitute an important environmental risk factor for neurodegenerative diseases in humans. PMID:26349946

  12. Influence of sulfur dioxide on metabolism and distribution of benzo[a]pyrene in isolated perfused rabbit lung

    International Nuclear Information System (INIS)

    An isolated perfused lung (IPL) preparation was used to investigate the effects of SO2 (1 to 2 ppM) on the metabolism of benzo[a]pyrene (BaP), a ubiquitous potent carcinogen that has been associated with the increased incidence of human brochiogenic carcinoma in occupational and urban populations. [14C]BaP, with and without crude air particulate (CAP), was administered intracheally to the IPL in conjunction with SO2 or after pretreatment of the whole animal with SO2. Metabolites were isolated from serial blood samples up to 3 h after the administration of [14C]BaP to the IPL. Metabolites were also isolated from lung tissue, washout fluid, macrophage, and trachea and bronchi at the end of the perfusion at 180 min. Patterns of BaP metabolites were determined by thin-layer and high-performance liquid chromatography and liquid scintillation counting. SO2 given in conjunction with BaP on the IPL or given to the whole animal followed by BaP on the IPL, in comparison with BaP only on the IPL, resulted in a twofold increase in the total rate of appearance of metabolites of BaP in the blood with changes in the metabolic pattern. SO2 given in conjunction with BaP and CAP on the IPL, in comparison with BaP plus SO2 on the IPL, resulted in a threefold decrease in the total rate of appearance of metabolites of BaP in the blood with changes in the metabolic pattern

  13. Metabolism of benzo(a)pyrene by aortic subcellular fractions in the setting of abdominal aortic aneurysms.

    Science.gov (United States)

    Ramesh, A; Prins, P A; Perati, P R; Rekhadevi, P V; Sampson, U K

    2016-01-01

    As exposure to polycyclic aromatic hydrocarbons (PAHs; a family of environmental toxicants) have been implicated in cardiovascular diseases, the ability of the aortic tissue to process these toxicants is important from the standpoint of abdominal aortic aneurysms and atherosclerosis. Benzo(a)pyrene (B(a)P), a representative PAH compound is released into the environment from automobile exhausts, industrial emissions, and considerable intake of B(a)P is also expected in people who are smokers and barbecued red meat eaters. Therefore, knowledge of B(a)P metabolism in the cardiovascular system will be of importance in the management of vascular disorders. Toward this end, subcellular fractions (nuclear, cytosolic, mitochondrial, and microsomal) were isolated from the aortic tissues of Apo E mice that received a 5 mg/kg/week of B(a)P for 42 days and 0.71 mg/kg/day for 60 days. The fractions were incubated with 1 and 3 μM B(a)P. Post incubation, samples were extracted with ethyl acetate and analyzed by reverse-phase HPLC. Microsomal B(a)P metabolism was greater than the rest of the fractions. The B(a)P metabolite levels generated by all the subcellular fractions showed a B(a)P exposure concentration-dependent increase for both the weekly and daily B(a)P treatment categories. The preponderance of B(a)P metabolites such as 7,8-dihydrodiol, 3,6-, and 6,12-dione metabolites are interesting due to their reported involvement in B(a)P-induced toxicity through oxidative stress. PMID:26530167

  14. Effect of benzo[a]pyrene on detoxification and the activity of antioxidant enzymes of marine microalgae

    Science.gov (United States)

    Shen, Chen; Miao, Jingjing; Li, Yun; Pan, Luqing

    2016-04-01

    The objective of this study was to examine the effect of benzo[a]pyrene (BaP) on the detoxification and antioxidant systems of two microalgae, Isochrysis zhanjiangensis and Platymonas subcordiformis. In our study, these two algae were exposed to BaP for 4 days at three different concentrations including 0.5 μg L-1 (low), 3 μg L-1 (mid) and 18 μg L-1 (high). The activity of detoxification enzymes, ethoxyresorufin O-deethylase (EROD) and glutathione S-transferase (GST) increased in P. subcordiformis in all BaP-treated groups. In I. zhanjiangensis, the activity of these two enzymes increased at the beginning of exposure, and then decreased in the groups treated with mid- and high BaP. The activity of antioxidant enzyme superoxide dismutase (SOD) increased in I. zhanjiangensis in all BaP-treated groups, and then decreased in high BaP-treated group, while no significant change was observed in P. subcordiformis. The activity of antioxidant enzyme catalase (CAT) increased in I. zhanjiangensis and P. subcordiformis in all BaPtreated groups. The content of malondialdehyde (MDA) in Isochrysis zhanjiangensis increased first, and then decreased in high BaP-treated group, while no change occurred in P. subcordiformis. These results demonstrated that BaP significantly influenced the activity of detoxifying and antioxidant enzymes in microalgae. The metabolic related enzymes (EROD, GST and CAT) may serve as sensitive biomarkers of measuring the contamination level of BaP in marine water.

  15. Exposure of sea bream (Sparus aurata) to toxic concentrations of benzo[a]pyrene: possible human health effect.

    Science.gov (United States)

    Zena, R; Speciale, A; Calabrò, C; Calò, M; Palombieri, D; Saija, A; Cimino, F; Trombetta, D; Lo Cascio, P

    2015-12-01

    Polycyclic aromatic hydrocarbons (PAHs) can accumulate in the food chain, due to their lipophilic properties. Fish can accumulate contaminants including PAHs and frequent consumption of such contaminated fish can pose risk to human health. The aim of this study was to clarify if acute exposure of sea bream (Sparus aurata, a fish species of great economic importance in the Atlantic and Mediterranean areas) to a PAH, benzo[a]pyrene (B[a]P), at a dose that can induce CYP1A and pathological changes in fish gills, liver and muscle, can induce accumulation in muscle. We investigated the cytotoxic effects (as changes in cell viability, DNA laddering and glutathione content) of in vitro exposure of human peripheral blood mononuclear cells (PBMCs) to organic extracts obtained from muscle of sea breams previously exposed via water to B[a]P (2mg/l, for 12, 24 and 72 h). At this level of exposure, B[a]P caused morphological changes, inflammatory response and CYP1A induction not only in sea bream gills and liver but also in muscle; furthermore, in fish muscle we observed a substantial B[a]P accumulation, which may be associated with the increased CYP1A activity in liver and especially in muscle. However, when PBMCs were exposed to organic extracts obtained from sea bream muscle contaminated with B[a]P, a toxic, although modest effect was revealed, consisting in a significant decrease in cell glutathione levels without alterations in cell viability and DNA laddering. This suggests that consumption of sea breams from B[a]P contaminated waters might represent a risk for human health. PMID:26232038

  16. Toxicogenomic outcomes predictive of forestomach carcinogenesis following exposure to benzo(a)pyrene: Relevance to human cancer risk

    International Nuclear Information System (INIS)

    Forestomach tumors are observed in mice exposed to environmental carcinogens. However, the relevance of this data to humans is controversial because humans lack a forestomach. We hypothesize that an understanding of early molecular changes after exposure to a carcinogen in the forestomach will provide mode-of-action information to evaluate the applicability of forestomach cancers to human cancer risk assessment. In the present study we exposed mice to benzo(a)pyrene (BaP), an environmental carcinogen commonly associated with tumors of the rodent forestomach. Toxicogenomic tools were used to profile gene expression response in the forestomach. Adult Muta™Mouse males were orally exposed to 25, 50, and 75 mg BaP/kg-body-weight/day for 28 consecutive days. The forestomach was collected three days post-exposure. DNA microarrays, real-time RT-qPCR arrays, and protein analyses were employed to characterize responses in the forestomach. Microarray results showed altered expression of 414 genes across all treatment groups (± 1.5 fold; false discovery rate adjusted P ≤ 0.05). Significant downregulation of genes associated with phase II xenobiotic metabolism and increased expression of genes implicated in antigen processing and presentation, immune response, chemotaxis, and keratinocyte differentiation were observed in treated groups in a dose-dependent manner. A systematic comparison of the differentially expressed genes in the forestomach from the present study to differentially expressed genes identified in human diseases including human gastrointestinal tract cancers using the NextBio Human Disease Atlas showed significant commonalities between the two models. Our results provide molecular evidence supporting the use of the mouse forestomach model to evaluate chemically-induced gastrointestinal carcinogenesis in humans. - Highlights: • Benzo(a)pyrene-mediated transcriptomic response in the forestomach was examined. • The immunoproteosome subunits and MHC class I

  17. Transcriptomics responses in marine diatom Thalassiosira pseudonana exposed to the polycyclic aromatic hydrocarbon benzo[a]pyrene.

    Directory of Open Access Journals (Sweden)

    Raquel N Carvalho

    Full Text Available Diatoms are unicellular, photosynthetic, eukaryotic algae with a ubiquitous distribution in water environments and they play an important role in the carbon cycle. Molecular or morphological changes in these species under ecological stress conditions are expected to serve as early indicators of toxicity and can point to a global impact on the entire ecosystem. Thalassiosira pseudonana, a marine diatom and the first with a fully sequenced genome has been selected as an aquatic model organism for ecotoxicological studies using molecular tools. A customized DNA microarray containing probes for the available gene sequences has been developed and tested to analyze the effects of a common pollutant, benzo(apyrene (BaP, at a sub-lethal concentration. This approach in diatoms has helped to elucidate pathway/metabolic processes involved in the mode of action of this pollutant, including lipid metabolism, silicon metabolism and stress response. A dose-response of BaP on diatoms has been made and the effect of this compound on the expression of selected genes was assessed by quantitative real time-PCR. Up-regulation of the long-chain acyl-CoA synthetase and the anti-apoptotic transmembrane Bax inhibitor, as well as down-regulation of silicon transporter 1 and a heat shock factor was confirmed at lower concentrations of BaP, but not the heat-shock protein 20. The study has allowed the identification of molecular biomarkers to BaP to be later on integrated into environmental monitoring for water quality assessment.

  18. Reduction of benzo[a]pyrene with acid-activated magnesium metal in ethanol: A possible application for environmental remediation

    International Nuclear Information System (INIS)

    Highlights: ► In this study we examine the use of Mg-ethanol for the partial reduction of PAHs at room temperature. ► The reduction of B[a]P occurred after the activation of Mg with acetic acid. ► This reducing system transformed 94% of B[a]P and produce six hydrogenated derivatives in 24 h. ► This technique can be a cheap alternative to current PAH remediation and hydrogenation methods. - Abstract: Persistent organic pollutants (POPs) are a well-known threat to the environment. Substances such as polycyclic aromatic hydrocarbons (PAHs) in contaminated soils and sediments can have severe and long-term effects on human and environmental health. There is an urgent need for the development of safe technologies for their effective degradation. Here we present a new technique using ball-milled magnesium powder and ethanol solvent as a convenient electron transfer/proton source for the partial reduction of PAHs under ambient conditions. The rates of degradation were determined while evaluating the influences of acetic acid and type of ball-milled magnesium added to the reaction mixture. The results of these triplicate studies indicate that with the use of acetic acid as an activator and ball-milled magnesium carbon (Mg/C), this reducing system (Mg–EtOH) is able to achieve a 94% conversion of 250 μg/mL of toxic benzo[a]pyrene into a mixture of less toxic and partially hydrogenated polycyclic compounds within 24 h. This methodology can be used as a combined process involving ethanol washing followed by reduction reaction and it can also be considered as an easy handling and efficient alternative process to the catalytic hydrogenation of PAHs.

  19. Biomarker responses in persian sturgeon (Acipenser persicus exposed to benzo-a-pyrene and beta-naphthoflavone

    Directory of Open Access Journals (Sweden)

    Karimzadeh Katayoon

    2013-01-01

    Full Text Available Biotransformation enzymes of xenobiotics (ethoxyresorufin-O-deethylase, cytochrome P4501A1 content and glutathione-S-transferase were investigated in the liver of Persian Sturgeon (Acipenser persicus after a 96-hour exposure to polycyclic aromatic hydrocarbons (PAHs, premutagenic benzo[a]pyrene (BaP and beta-naphthoflavone (BNF. The fish were injected 10 mg/kg wet-body weight in corn oil for 96 hours every days. Ethoxyresorufin-O-deethylase activity (EROD and glutathione s-transferase activity (GST were measured in the fish liver. Cytochrome P4501A1 (CYP1A1 content was estimated by indirect enzyme-linked immunosorbent assay (ELISA. The response appeared as early as 12 hours post exposure. A time-dependent response was observed in the EROD activity, being significantly higher at 48 hours post exposure to 10 mg/kg of BaP. The greatest induction occurred in the fish treated with 10 mg/kg BaP, in which a 32.1- fold increase in EROD activity was observed. Results showed that EROD activity in A. persicus is significantly increased by BaP and BNF treatments. Both chemicals showed higher values of EROD activity compared to the liver CYP1A content. There was a rise in glutathione-S-transferase activity in fish exposed to BNF, but no increase was observed in fish treated with BaP. The results showed that hepatic CYP1A expression in terms of induction of EROD activity might be suited as a biomarker of organic contamination in aquatic environments and led to lower sensitivity of the second phase in the detoxification enzyme.

  20. The arbuscular mycorrhizal Rhizophagus irregularis activates storage lipid biosynthesis to cope with the benzo[a]pyrene oxidative stress.

    Science.gov (United States)

    Calonne, Maryline; Fontaine, Joël; Debiane, Djouher; Laruelle, Frédéric; Grandmougin-Ferjani, Anne; Lounès-Hadj Sahraoui, Anissa

    2014-01-01

    The phytoremediation assisted by arbuscular mycorrhizal fungi (AMF) could constitute an ecological and economic method to restore polycyclic aromatic hydrocarbon (PAH) polluted soils. Unfortunately, little is known about the PAH impact on the beneficial symbiotic AMF. Using radiolabelling experiments, our work aims to understand how benzo[a]pyrene (B[a]P), a representative of high molecular weight PAH, acts on the AMF lipid metabolism. Our results showed decreases in the sterol precursors as well as in total phospholipid quantities, in link with the [1-(14)C]acetate incorporation decreases in these lipids. Interestingly, a concomitant increase of [1-(14)C]acetate incorporation by 29.5% into phosphatidylcholine with its content decrease in Rhizophagus irregularis extraradical mycelium was observed, suggesting a membrane regeneration. A second concomitant increase (estimated to 69%) of [1-(14)C]acetate incorporation into triacylglycerols (TAG) with the content decrease was also observed. This suggests a fungal TAG biosynthesis activation probably to offset the decrease in storage lipid content when the fungus was grown under B[a]P pollution. In addition, our findings showed that lipase activity was induced by more than 3 fold in the presence of B[a]P in comparison to the control indicating that the drop in TAG content could be a consequence of their active degradation. Taken together, our data suggest the involvement of the fungal TAG metabolism to cope B[a]P toxicity through two means: (i) by providing carbon skeletons and energy necessary for membrane regeneration and/or for B[a]P translocation and degradation as well as (ii) by activating the phosphatidic acid and hexose metabolisms which may be involved in cellular stress defence. PMID:24246754

  1. Induction of micronuclei by X radiation and various chemical agents in red blood cells of Pleurodeles waltl. Uptake, release and excretion of one of them: benzo(a)pyrene

    International Nuclear Information System (INIS)

    The first part of the study is concerned with the effects of X radiation and of various substances dissolved in the breeding water (carbaryl, N-nitrosocarbaryl, benzo(a)pyrene, formol, cafeine, colchicine...) on the formation of micronuclei in red blood cells of Pleurodele larvae. The curves of the dose-effect relationships and of the kinetics of micronuclei formation are established for X radiation and benzo(a)pyrene. In the second part, a scintigraphic study concerning benzo(a)pyrene uptake, release and excretion by larvae, is presented. This study enables the dose-effect curve and the kinetics of micronuclei formation for this substance, to be interpreted. This study must allow the development of a cytogenetic test for the detection of radiomimetic substances in aqueous medium. Pleurodele is proposed as a new animal for the study of genetic toxicology

  2. Development and validation of SPE-HPLC method for the determination of carbamazepine and its metabolites carbamazepine epoxide and carbamazepine trans-diol in plasma

    Directory of Open Access Journals (Sweden)

    Spasić Mirjana

    2012-01-01

    Full Text Available SPE-HPLC method has been developed and validated for rapid analysis of carbamazepine and its two metabolites carbamazepine epoxide and carbamazepine trans-diol in human plasma. The analysis was performed using C18 Bakerbond-BDC analytical column (250 mm x 4.6 mm i.d., particle size 5 μm. The optimal conditions for the separation were established with the mobile phase acetonitrile - 10 mM phosphate buffer, pH 7.0 (30:70, v/v at the flow rate of 1.5 mL min-1, temperature 35°C, and UV detection at 210 nm. Total run time was about 8 minutes. SPE procedure for extraction of the analytes from plasma sample was developed using Oasis HLB cartridges and subsequently eluate was injected into the HPLC system for analysis. Afterwards, SPE-HPLC method was subjected to validation. Linearity was obtained over the concentration range of 0.2-25 μg/mL for carbamazepine, carbamazepine epoxide and carbamazepine trans-diol with correlation coefficients higher than 0.995. The method showed good intra-day and inter-day precision with relative standard deviation below 7.96%, while accuracy ranged from 92.09% to 108.5% for all analytes. Finally, the method was successfully applied to analysis of plasma samples of epileptic patients in monotherapy and polytherapy. [Acknowledgments. Projekat Ministarstva nauke Republike Srbije, br. OI 172033].

  3. Diacyltransferase Activity and Chain Length Specificity of Mycobacterium tuberculosis PapA5 in the Synthesis of Alkyl β-Diol Lipids

    Energy Technology Data Exchange (ETDEWEB)

    Touchette, Megan H.; Bommineni, Gopal R.; Delle Bovi, Richard J.; Gadbery, John; Nicora, Carrie D.; Shukla, Anil K.; Kyle, Jennifer E.; Metz, Thomas O.; Martin, Dwight W.; Sampson, Nicole S.; Miller, W. T.; Tonge, Peter J.; Seeliger, Jessica C.

    2015-09-08

    Although classified as Gram-positive bacteria, Corynebacterineae possess an asymmetric outer membrane that imparts structural and thereby physiological similarity to more distantly related Gram-negative bacteria. Like lipopolysaccharide in Gram-negative bacteria, lipids in the outer membrane of Corynebacterineae have been associated with the virulence of pathogenic species such as Mycobacterium tuberculosis (Mtb). For example, Mtb strains that lack long, branched-chain alkyl esters known as dimycocerosates (DIMs) are significantly attenuated in model infections. The resultant interest in the biosynthetic pathway of these unusual virulence factors has led to the elucidation of many of the steps leading to the final esterification of the alkyl beta-diol, phthiocerol, with branched-chain fatty acids know as mycocerosates. PapA5 is an acyltransferase implicated in these final reactions. We here show that PapA5 is indeed the terminal enzyme in DIM biosynthesis by demonstrating its dual esterification activity and chain-length preference using synthetic alkyl beta-diol substrate analogues. Applying these analogues to a series of PapA5 mutants, we also revise a model for the substrate binding within PapA5. Finally, we demonstrate that the Mtb Ser/Thr kinase PknB modifies PapA5 on three Thr residues, including two (T196, T198) located on an unresolved loop. These results clarify the DIM biosynthetic pathway and suggest possible mechanisms by which DIM biosynthesis may be regulated by the post-translational modification of PapA5.

  4. Enhancement effect of p-menthane-3,8-diol on in vitro permeation of antipyrine and indomethacin through Yucatan micropig skin.

    Science.gov (United States)

    Fujii, Makiko; Takeda, Yasuhiro; Yoshida, Minako; Matsumoto, Mitsuo; Watanabe, Yoshiteru

    2004-07-01

    The enhancing effect of p-Menthane-3,8-diol (MDO) on skin permeation of antipyrine (ANP) and indomethacin (IM) through Yucatan micropig skin in vitro was compared with 1-menthol. p-Menthane-3,8-diol is a metabolite of 1-menthol and has little odor. It is easy to combine the vehicle because of lower lipophilicity than 1-menthol. All formulations contained 40% (v/v) ethanol. The permeation of ANP increased with MDO about three times that without enhancer by increasing ANP concentration in the skin. However, the MDO effect was about a quarter that of 1-menthol. The permeation of IM with MDO was about 15 times that with no enhancer and it was almost the same as that with 1-menthol. The lag time of permeation was not significantly changed by MDO, which was not so in the case of 1-menthol. Skin concentration of IM increased about 11 times and six times with MDO and 1-menthol, respectively. MDO and 1-menthol partitioned to the skin relatively high concentrations, 5.9 and 2.5 mg/ cm3, respectively. The solubility of IM in the skin was improved by MDO, and consequently, the permeation of IM was enhanced. PMID:15285341

  5. Experimental Study of Structure-Energy Changes in Molecules and Crystals of 2,2-Dinitropropane-1,3-diol Caused by Temperature Variations

    Science.gov (United States)

    Golovina, N. I.; Raevskii, A. V.; Fedorov, B. S.; Gusakovskaya, I. G.; Trofimova, R. F.; Chukanov, N. V.; Vozchikova, S. A.; Shilov, G. V.; Tarasov, V. P.; Erofeev, L. N.; Atovmyan, L. O.

    2001-03-01

    Crystals of 2,2-dinitropropane-1,3-diol were prepared and grown at different temperatures. An X-ray analysis was used to study the structure of three phases (1, 2 and 3) of the 2,2-dinitropropane-1,3-diol crystals. The calorimetric study of the crystals temperature behavior (1) showed the presence of two phase transitions in the regions of T=309 K and T=340 K, as well as crystals (2) with a phase transition at T=340 K. Observations in a hot stage with the optical microscope phase transitions for separate crystals were made. X-ray diffraction studies of polycrystalline samples (1) for temperatures increasing up to the temperatures of phase transitions I and II demonstrated that phase transition I is followed by conversion of crystals 1 into 2, and transition II is connected with conversion of crystals 2 into a disordered body-centered structure. The temperature behavior of the bands of symmetric N-O stretching vibrations of nitro groups and stretching vibrations of O-H groups was studied by IR spectroscopy. The temperature dependence of hydrogen bonds redistribution and nitro group reorientational dynamics was examined. Data on the structure-dynamic rearrangement in the crystal lattice of the examined compound were obtained by the NMR pulse method in the solid phase using relaxational free induction decay of protons. The kinetic parameters of the process were obtained.

  6. Selective Enrichment and MALDI-TOF MS Analysis of Small Molecule Compounds with Vicinal Diols by Boric Acid-Functionalized Graphene Oxide

    Science.gov (United States)

    Zhang, Jing; Zheng, Xiaoling; Ni, Yanli

    2015-08-01

    In this study, a 4-vinylphenylboronic acid-functionalized graphene oxide (GO) material was prepared via atom-transfer radical polymerization (ATRP) method and applied for the first time as a novel matrix for the selective enrichment and analysis of small-molecule compounds with vicinal diols, which have been the focus of intense research in the field of life science, by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in positive-ion mode. There are two main factors playing a decisive role in assisting laser D/I process comparing to some traditional matrices: (1) GO provides π-conjugated system by itself for laser absorption and energy transfer; (2) the modified 4-vinylphenylboronic acid can selectively capture small-molecule compounds with vicinal diols. The results demonstrate that the novel material has distinct advantages over previously reported matrices in enriching and assisting the highly efficient ionization of target molecules for mass spectrometry analysis. This work indicates a new application branch for graphene-based matrices and provides an alternative solution for small-molecules analysis.

  7. Mikrosomale Biotransformation von Benzo[ghi]perylen, einem mutagenen polyaromatischen Kohlenwasserstoff ohne das Strukturelement der Bay-Region des kanzerogenen Benzo[a]pyrens

    OpenAIRE

    Grupe, Stefanie

    2005-01-01

    Kanzerogene polyaromatische Kohlenwasserstoffe (PAKs), wie Benzo[a]pyren, besitzen eine Bay-Region mit ortho-kondensiertem Benzoring. Dadurch ist die enzymatische Bildung von Bay-Region-Dihydrodiolepoxiden (Oxiranylring in der sterisch abgeschirmten Molekülbucht) möglich, die als ultimal kanzerogene Metaboliten der PAKs gelten. Diese lösen durch DNA-Modifikation Primärläsionen aus, die, sofern sie nicht enzymatisch repariert werden, bei der DNA-Replikation Fehler verursachen (Mu-tationen). De...

  8. Immunogenicity of a Promiscuous T Cell Epitope Peptide Based Conjugate Vaccine against Benzo[a]pyrene: Redirecting Antibodies to the Hapten

    OpenAIRE

    Schellenberger, Mario T; Grova, Nathalie; Farinelle, Sophie; Willième, Stéphanie; Revets, Dominique; Muller, Claude P.

    2012-01-01

    The prototype polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P) is an environmental pollutant and food contaminant of epidemiological importance. To protect against adverse effects of this ubiquitous carcinogen, we developed an immunoprophylactic strategy based on a B[a]P-protein conjugate vaccine to induce B[a]P specific antibodies (Grova et al., Vaccine. 2009;27:4142–51). Here, we investigated in mice the efficacy of B[a]P-peptide conjugates based on promiscuous T cell epitopes (TCE) i...

  9. Determination of benzo[a]pyrene in cigarette mainstream smoke by using mid-infrared spectroscopy associated with a novel chemometric algorithm.

    Science.gov (United States)

    Zhang, Yan; Zou, Hong-Yan; Shi, Pei; Yang, Qin; Tang, Li-Juan; Jiang, Jian-Hui; Wu, Hai-Long; Yu, Ru-Qin

    2016-01-01

    Determination of benzo[a]pyrene (BaP) in cigarette smoke can be very important for the tobacco quality control and the assessment of its harm to human health. In this study, mid-infrared spectroscopy (MIR) coupled to chemometric algorithm (DPSO-WPT-PLS), which was based on the wavelet packet transform (WPT), discrete particle swarm optimization algorithm (DPSO) and partial least squares regression (PLS), was used to quantify harmful ingredient benzo[a]pyrene in the cigarette mainstream smoke with promising result. Furthermore, the proposed method provided better performance compared to several other chemometric models, i.e., PLS, radial basis function-based PLS (RBF-PLS), PLS with stepwise regression variable selection (Stepwise-PLS) as well as WPT-PLS with informative wavelet coefficients selected by correlation coefficient test (rtest-WPT-PLS). It can be expected that the proposed strategy could become a new effective, rapid quantitative analysis technique in analyzing the harmful ingredient BaP in cigarette mainstream smoke. PMID:26703252

  10. Benzo(a)pyrene oxidation, conjugation and disposition in the isolated perfused rabbit lung: role of the glutathione S-transferases.

    Science.gov (United States)

    Ball, L M; Plummer, J L; Smith, B R; Bend, J R

    1979-10-01

    The isolated perfused rabbit lung metabolised 7--11 % of 20 mumol of [14C]-benzo(a)pyrene added in the perfusion medium in 1 h. The major metabolite formed was 3-hydroxybenzo(a)pyrene, both free (30--40 % of the total metabolites) and conjugated (4 % of total metabolites). Quinones comprised 15 % of the total and metabolism at the 9, 10 position accounted for a further 10 %. Forty per cent of the water-soluble metabolites was chromatographically identical to the glutathione conjugate of benzo(a)pyrene 4,5-oxide. Sulphate and glucuronide conjugates were formed in small but detectable amounts, principally from phenols, but also from dihydrodiols. After 1 h the more water-soluble conjugates had diffused from the lung into the perfusion medium, but the majority (60--90 %) of the metabolic products were still concentrated within the lung. The lung's limited ability to conjugate its major metabolites of benzo(a)pyrene with sulphuric or glucuronic acid, coupled with slow elimination of the products formed, particularly dihydrodiols may contribute to the susceptibility of this organ to polycyclic aromatic hydrocarbon-induced carcinogenesis. PMID:522517

  11. Anti-inflammatory and Immune Regulatory Properties of 5-Androsten-3{beta}, 17{beta}-Diol (HE2100), and Synthetic Analogue HE3204: Implications for Treatment of Autoimmune Diseases.

    NARCIS (Netherlands)

    Auci, D.; Nicoletti, F.; Mangano, K.; Pieters, R.; Nierkens, S.; Morgan, L.; Offner, H.; Frincke, J.; Reading, C.

    2005-01-01

    5-Androsten-3beta, 17beta-diol (HE2100), and a synthetic analogue HE3204 are regarded as immune-regulating hormones, because both induce changes in the reporter antigen-popliteal lymph node assay (RA-PLNA). Mice were injected in the footpad with either HE2100 or HE3204 (0.01-3 mg), and a nonsensitiz

  12. Thermodynamics and activity coefficients at infinite dilution for organic solutes, water and diols in the ionic liquid choline bis(trifluoromethylsulfonyl)imide

    International Nuclear Information System (INIS)

    Graphical abstract: - Highlights: • Measurements of activity coefficients at infinite dilution using GLC. • 63 Solvents including water and 6 diols in the ionic liquid choline bis(trifluoromethylsulfonyl)imide. • High selectivity for thiophene/heptane and pyridine/heptane separation. • The excess thermodynamic functions and the (gas + liquid) partition coefficients were calculated. - Abstract: The activity coefficients at infinite dilution, γ13∞, for 63 solutes, including alkanes, cycloalkanes, alkenes, alkynes, aromatic hydrocarbons, alcohols, water, thiophene, ethers, ketones, esters, aldehyde, acetonitrile, pyridine and 1-nitropropane and 6 diols in the ionic liquid (IL) choline bis(trifluoromethylsulfonyl)imide, [N1112OH][NTf2] were determined by (gas + liquid) chromatography at six temperatures in range of (318.15 to 368.15) K and at three temperatures for diols in the range of (388.15 to 418.15) K. The thermodynamic functions at infinite dilution as partial molar excess Gibbs free energy, ΔG1E,∞, enthalpy ΔH1E,∞, and entropy term TrefΔS1E,∞ were calculated from the experimental γ13∞ values obtained over the temperature range. The density of [N1112OH][NTf2] was measured within temperature range (313.15 to 353.15) K. The (gas + liquid) partition coefficient KL was calculated for all solutes. The values of selectivity and capacity for a few separation problems as hexane/benzene, cyclohexane/benzene, heptane/thiophene at T = 328.15 K were calculated from γ13∞ and compared to literature values for similar ionic liquids, N-methyl-2-pyrrolidinone (NMP), and sulfolane. In comparison with the former measured ammonium-based ILs and the morpholinium-based ILs, the [N1112OH][NTf2] shows average selectivity for the separation of aromatic hydrocarbons, or sulfur compound from aliphatic hydrocarbons, and very high selectivity for pyridine/heptane separation. New data show that [N1112OH][NTf2] IL may be proposed as an alternative solvent for the

  13. Determinação de benzo(apireno em pescados Determination of benzo(apyrene in fish products

    Directory of Open Access Journals (Sweden)

    Antonio Azeredo

    2006-03-01

    Full Text Available No presente estudo, peixes, camarões, mexilhões e carnes de siri frescos e processados, comercializados na região metropolitana de Campinas (SP, foram analisados quanto à presença de benzo(apireno (B(aP. A metodologia utilizada envolveu extração com n-hexano, limpeza em Sep-Pak sílica plus e determinação por Cromatografia Líquida de Alta Eficiência com Detector de Fluorescência. A presença de B(aP foi detectada em todas as amostras analisadas (n=35, em quantidades variando na faixa de 0,03 a 4,54 µg/kg. Os maiores níveis de contaminação foram encontrados em produtos defumados (níveis médios=2,5 µg/kg e mexilhões (níveis médios=2,4 µg/kg. Considerando-se o potencial carcinogênico desse contaminante e a importância desse grupo de alimentos na dieta, um programa de monitoramento deve ser iniciado para identificar e controlar a fonte de contaminação de pescados por B(aP.In the present study samples of fresh and processed fish, shrimp, mussels and crab meat commercialized in the metropolitan area of Campinas (SP, Brazil were analysed for benzo(apyrene (B(aP. The methodology involved extraction with n-hexane, clean-up on Sep-Pak silica plus and determination by High Performance Liquid Chromatography with a Fluorescence Detector. B(aP was detected in all samples analysed (n=35 at levels ranging from to 0.03 a 4.54 µg/kg. The highest content of B(aP was found in smoked products (mean level=2.5 µg/kg and mussels (mean level=2.4 µg/kg. In view of the carcinogenic potential of this widely distributed contaminant and the importance of seafood in the daily diet of fisherman communities, a monitoring program should be initiated to identify and control the source of contamination of seafood by B(aP.

  14. Effects of a cocarcinogen, ferric oxide, on the metabolism of benzo[a]pyrene in the isolated perfused lung

    International Nuclear Information System (INIS)

    An isolated perfused New Zealand rabbit lung preparation was used to investigate the effects of a cocarcinogen, ferric oxide (Fe2O3), on the metabolism of benzo[a]pyrene (BaP), a ubiquitous potent carcinogen that has been associated with the increased incidence of human bronchiogenic carcinoma in occupational and urban settings. [14C]-BaP was administered intratracheally to an isolated perfused lung (IPL) preparation with and without Fe2O3 after intraperitoneal pretreatment of the whole animal with BaP or intratracheal pretreatment of the whole animal with Fe2O3 and/or BaP. BaP and its metabolites were isolated from serial blood samples up to 180 min after administration of [14C]BaP to the IPL. BaP and its metabolites were also isolated from lung tissue, washout fluid, macrophage, and trachea bronchi at the end of the perfusion at 180 min. Patterns of BaP metabolites were determined by chromatographic techniques and liquid scintillation counting. Fe2O3 pretreatment to the whole animal or administration of Fe2O3 to the IPL altered BaP metabolism by the perfused lung. Fe2O3 pretreatment to the whole animal resulted in an increase in the total rate of appearance of metabolites of BaP in the blood, while Fe2O3 administration to the IPL resulted in a decrease in the total rate of appearance of BaP metabolites in the blood and inhibited the effect of pretreatment. These data suggest that pulmonary exposure to a known cocarcinogen, Fe2O3, in the presence of BaP results in increased production of dihydrodiols of BaP, which may be further metabolized to the ultimate carcinogenic form(s) of BaP. Therefore, Fe2O3 can enhance the metabolic activation of BaP by the lung, as well as act as a carrier for penetration and retention of BaP in the lung. 49 references, 6 tables

  15. Impact of benzo(a)pyrene, Cu and their mixture on the proteomic response of Mytilus galloprovincialis

    Energy Technology Data Exchange (ETDEWEB)

    Maria, V.L., E-mail: vmaria@ualg.pt [CIMA, Faculty of Sciences and Technology, University of Algarve, Campus de Gambelas, 8005-139 Faro (Portugal); Gomes, T., E-mail: tcgomes@ualg.pt [CIMA, Faculty of Sciences and Technology, University of Algarve, Campus de Gambelas, 8005-139 Faro (Portugal); Barreira, L., E-mail: lbarreir@ualg.pt [CCMAR, Faculty of Sciences and Technology, University of Algarve, Campus de Gambelas, 8005-139 Faro (Portugal); Bebianno, M.J., E-mail: mbebian@ualg.pt [CIMA, Faculty of Sciences and Technology, University of Algarve, Campus de Gambelas, 8005-139 Faro (Portugal)

    2013-11-15

    Highlights: •Distinct protein expression profiles dependent of BaP and Cu accumulation, metabolism and chemical interactions in mussels, Mytilus galloprovincialis. •Processes that involve adhesion and motility, cytoskeleton and cell structure, stress response, transcription regulation and energy metabolism are common mechanisms. •Traditional (ATP synthase, GST, HSP and actin) and novel biomarkers for BaP (ZFP), Cu (chitin synthase) and mixture (MVP) exposures identified in mussels. -- Abstract: In natural waters, chemical interactions between mixtures of contaminants can result in potential synergistic and/or antagonic effects in aquatic animals. Benzo(a)pyrene (BaP) and copper (Cu) are two widespread environmental contaminants with known toxicity towards mussels Mytilus spp. The effects of the individual and the interaction of BaP and Cu exposures were assessed in mussels Mytilus galloprovincialis using proteomic analysis. Mussels were exposed to BaP [10 μg L{sup −1} (0.396 μM)], and Cu [10 μg L{sup −1} (0.16 μM)], as well as to their binary mixture (mixture) for a period of 7 days. Proteomic analysis showed different protein expression profiles associated to each selected contaminant condition. A non-additive combined effect was observed in mixture in terms of new and suppressed proteins. Proteins more drastically altered (new, suppressed and 2-fold differentially expressed) were excised and analyzed by mass spectrometry, and eighteen putatively identified. Protein identification demonstrated the different accumulation, metabolism and chemical interactions of BaP, Cu and their mixture, resulting in different modes of action. Proteins associated with adhesion and motility (catchin, twitchin and twitchin-like protein), cytoskeleton and cell structure (α-tubulin and actin), stress response (heat shock cognate 71, heat shock protein 70, putative C1q domain containing protein), transcription regulation (zinc-finger BED domain-containing and nuclear

  16. Impact of benzo(a)pyrene, Cu and their mixture on the proteomic response of Mytilus galloprovincialis

    International Nuclear Information System (INIS)

    Highlights: •Distinct protein expression profiles dependent of BaP and Cu accumulation, metabolism and chemical interactions in mussels, Mytilus galloprovincialis. •Processes that involve adhesion and motility, cytoskeleton and cell structure, stress response, transcription regulation and energy metabolism are common mechanisms. •Traditional (ATP synthase, GST, HSP and actin) and novel biomarkers for BaP (ZFP), Cu (chitin synthase) and mixture (MVP) exposures identified in mussels. -- Abstract: In natural waters, chemical interactions between mixtures of contaminants can result in potential synergistic and/or antagonic effects in aquatic animals. Benzo(a)pyrene (BaP) and copper (Cu) are two widespread environmental contaminants with known toxicity towards mussels Mytilus spp. The effects of the individual and the interaction of BaP and Cu exposures were assessed in mussels Mytilus galloprovincialis using proteomic analysis. Mussels were exposed to BaP [10 μg L−1 (0.396 μM)], and Cu [10 μg L−1 (0.16 μM)], as well as to their binary mixture (mixture) for a period of 7 days. Proteomic analysis showed different protein expression profiles associated to each selected contaminant condition. A non-additive combined effect was observed in mixture in terms of new and suppressed proteins. Proteins more drastically altered (new, suppressed and 2-fold differentially expressed) were excised and analyzed by mass spectrometry, and eighteen putatively identified. Protein identification demonstrated the different accumulation, metabolism and chemical interactions of BaP, Cu and their mixture, resulting in different modes of action. Proteins associated with adhesion and motility (catchin, twitchin and twitchin-like protein), cytoskeleton and cell structure (α-tubulin and actin), stress response (heat shock cognate 71, heat shock protein 70, putative C1q domain containing protein), transcription regulation (zinc-finger BED domain-containing and nuclear receptor

  17. 3H thymidine an indicator of benzo(a)pyrene induced lung carcinogenesis: role of quercetin and curcumin

    International Nuclear Information System (INIS)

    Full text: Lung cancer is responsible for most of the cancer related deaths and calls for new approaches to control the menace. In the present study chemopreventive efficacy of curcumin and quercetin was investigated against benzo(a)pyrene (BP) induced lung carcinogenesis. The mice were segregated into five groups which included normal control, BP treated, BP+curcumin treated, BP+quercetin treated and BP+curcumin+quercetin treated groups. The morphological and histological analyses of tumor nodules confirmed lung carcinogenesis, after 22 weeks of single i.p. injection of BP at a dose of 100 mg/Kg body weight to mice. Tumor incidence and tumor multiplicity were observed to be 88% and 1.75, respectively in the BP treated mice. A statistically significant increase in the uptake of 3H thymidine indicative of increased DNA synthesis which in turn is the marker of uncontrolled cancer cell proliferation, was observed in the lung slices of BP treated mice. Further, BP treatment resulted in marked disruption in the histoarchitecture of lungs. Nuclei were enlarged, thickening of epithelium was seen. Structure-less masses of cells were visible all over. Nuclear pleomorphism and decreased cytoplasmic contents were also observed in BP treated mice. Squamous epithelial metaplasia, severe epithelial thickening and alveolar vocuolizations in distal airways indicative of lung carcinogensis were also observed in the BP treated mice. Supplementation with curcumin alone resulted in a significant decrease in the tumor incidence as well as tumor multicity which were observed to be 77% and 1.42 respectively. Also, quercetin significantly decreased tumor incidence and tumor multiplicity to 70% and 1.28 respectively. However, upon combined supplementation with phytochemicals, an appreciable decrease in the tumor incidence and multiplicity was observed which was found to be 60% and 1.00 respectively. Further, Supplementation with curcumin alone to BP treated mice resulted in statistically

  18. Zinc finger proteins and other transcription regulators as response proteins in benzo[a]pyrene exposed cells

    International Nuclear Information System (INIS)

    Proteomic analysis, which combines two-dimensional electrophoresis (2-DE) and mass spectrometry (MS), is an important approach to screen proteins responsive to specific stimuli. Benzo[a]pyrene (B[a]P), a prototype of polycyclic hydrocarbons (PAHs), is a potent procarcinogen generated from the combustion of fossil fuel and cigarette smoke. To further probe the molecular mechanism of mutagenesis and carcinogenesis, and to find potential molecular markers involved in cellular responses to B[a]P exposure, we performed proteomic analysis of whole cellular proteins in human amnion epithelial cells after B[a]P-treatment. Image visualization and statistical analysis indicated that more than 40 proteins showed significant changes following B[a]P-treatment (P<0.05). Among them, 20 proteins existed only in the control groups, while six were only present in B[a]P-treated cells. In addition, the expression of 10 proteins increased whereas 11 decreased after B[a]P-treatment. These proteins were subjected to in-gel tryptic digestion followed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) analysis. Using peptide mass fingerprinting (PMF) to search the nrNCBI database, we identified 22 proteins. Most of these proteins have unknown functions and have not been previously connected to a response to B[a]P exposure. To further annotate the characteristics of these proteins, GOblet analysis was carried out and results indicated that they were involved in multiple biological processes including regulation of transcription, cell proliferation, cell aging and other processes. However, expression changes were noted in a number of transcription regulators, including eight zinc finger proteins as well as SNF2L1 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 1), which is closely linked to the chromatin remodeling process. These data may provide new clues to further understand the implication of

  19. 17a-Ethynyl-5a-androstane-3a, 17 β-diol Treatment of MNU-Induced Mammary Cancer in Rats

    International Nuclear Information System (INIS)

    N-methyl-N-nitrosourea (MNU) induces estrogen-dependent mammary tumors in female Lewis rats. We explored the antineoplastic activity of a synthetic androstane derivative, 17 a-ethynyl-5a-androstane-3a, 17β-diol (HE3235), as a single agent or in combination with docetaxel compared to tamoxifen, anastrazole, and docetaxel mono therapies against MNU-induced mammary tumors in female Lewis rats. Treatment with HE3235 alone rapidly reduced tumor burden, similar in effect to tamoxifen and anastrozole. The combination of HE3235 with docetaxel was more effective than any single agent, although without apparent toxicity. Only HE3235 or HE3235 plus docetaxel continued to suppress tumor growth after cessation of treatment. HE3235 treatment increased immunohistochemical markers of apoptosis and expression of pro apoptotic genes and estrogen receptor beta and decreased expression of anti apoptotic genes, androgen receptor, and estrogen receptor alpha. These data warrant clinical investigation of HE3235 for breast cancer treatment.

  20. Binding, distribution, and clearance of 3H-benzo(a)pyrene-7,8-diol-9,10-epoxide from chromosomes of CHO cells

    International Nuclear Information System (INIS)

    The purpose of this study was to determine if the binding of a chemical carcinogen was random both within and between chromosomes. Chinese hamster ovary cells were exposed to 3H-labeled +/- anti[G-3H]-benzo(a)pyrene-7,8-diol-9,10-epoxide (3H-BPDE) and serially harvested. Autoradiographs were prepared and the distribution of silver grains over metaphase chromosomes was determined. The 3H-BPDE was randomly distributed down the length of the chromosome. The 3H-BPDE was rapidly removed from the chromosomes with 6% of the initial label remaining at 9 h after exposure. The distribution of silver grains between chromatids was nonrandom at 3 and 6 h after exposure, suggesting a differential removal of 3H-BPDE. 4 references, 4 figures

  1. THE EFFECT OF PENTACHLOROPHENOL ON DNA ADDUCT FORMATION IN C57B1/6 TRP53 +/+ AND C57B16 TRP53 -/- MICE EXPOSED TO BENZO[A]PYRENE MAY BE ASSOCIATED WITH P53 FUNCTION.

    Science.gov (United States)

    AbstractPrevious studies have shown that pentachlorophenol (PCP) has both potentiative and antagonistic effects on the genotoxicity of benzo[a]pyrene (B[a]P). It has been suggested that these effects are due to inhibition and/or induction of enzymes involved in the biotr...

  2. Mutations Induced by Benzo[a]pyrene and Dibenzo[a,l]pyrene in lacI Transgenic B6C3F1 Mouse Lung Result from Stable DNA Adducts

    Science.gov (United States)

    Dibenzo[a,l]pyrene (DB[a,l]P) and benzo[a]pyrene (B[a]P) are carcinogenic polycyclic aromatic hydrocarbons (PAH) that are each capable of forming a variety of covalent adducts with DNA. Some of the DNA adducts formed by these PAHs have been demonstrated to spontaneously depurina...

  3. Pulmonary gene and microRNA expression changes in mice exposed to benzo(a)pyrene by oral gavage

    International Nuclear Information System (INIS)

    Highlights: → The study examines pulmonary response in mice exposed to BaP by oral gavage. → We examined pulmonary gene and miRNA expression changes and measured DNA adducts. → We compare the mechanisms of action that operate in lungs relative to the liver. → We show differences in biological pathways activated in lungs versus the liver. → We suggest that liver miRNAs are less sensitive to perturbations than lung miRNAs. -- Abstract: Exposure to the environmental mutagen benzo(a)pyrene (BaP) alters the expression of AHR-responsive genes as well as genes involved in other pathways. We recently reported that exposure of adult mice to BaP resulted in a robust transcriptome response in the liver, but this was accompanied by a complete lack of change in microRNA (miRNA) expression. Since BaP exposure does not result in hepatocarcinogenicity, but does cause lung cancer, in the present study we examine the pulmonary mRNA and miRNA responses to BaP in the same mice. Adult male B6C3F1 mice were exposed to 150 and 300 mg/kg BaP by oral gavage for three consecutive days and sacrificed 4 h after the last exposure. Serum clinical chemistry was performed for both the doses to assess the general toxicity of BaP; a modest decrease in serum inorganic phosphorous was observed at both the doses. A small decrease in serum glucose following 150 mg/kg and alkaline phosphatase following 300 mg/kg BaP was observed. BaP-DNA adduct levels in whole lung and liver tissues were assessed by 32P postlabelling and similar dose dependent increases were observed for lung and liver. Using DNA microarrays, pulmonary mRNA and miRNA expressions were analysed. Over 1000 genes were statistically differentially expressed (p < 0.05). The perturbed pathways included oxidative stress, xenobiotic metabolism, cell proliferation, cell cycle, B and T-cell receptor signalling and primary immunodeficiency signalling pathways. Analysis of miRNA profiles revealed downregulation of miR-150, miR-142-5p, mi

  4. Cytochrome P450 system expression and DNA adduct formation in the liver of Zacco platypus following waterborne benzo(a)pyrene exposure: implications for biomarker determination.

    Science.gov (United States)

    Lee, Jin Wuk; Kim, Yong Hwa; Yoon, Seokjoo; Lee, Sung Kyu

    2014-09-01

    Benzo(a)pyrene (BaP) is a polycyclic aromatic hydrocarbon that causes mutations and tumor formation. Zacco platypus is a sentinel species that is suitable for monitoring aquatic environments. We studied cytochrome P450 system (CYP system) expression and DNA adduct formation in the liver of Z. platypus following waterborne exposure to BaP. The results showed both dose and time dependency. The significant induction levels of CYP system mRNA and protein reached maximums at 2 days and 14 days, respectively, and hepatosomatic index was maximally induced at 4 days during 14 days BaP exposure. DNA adduct formation was significantly induced compared to corresponding controls (t-test, p platypus is a useful species for assessing the risk of waterborne BaP exposure. PMID:23192953

  5. Bioavailability of benzo(a)pyrene and dehydroabietic acid from a few lake waters containing varying dissolved organic carbon concentrations to Daphnia magna

    International Nuclear Information System (INIS)

    Dissolved organic carbon (DOC) in natural waters consists of a great variety of organic molecules. Some of these molecules have been identified but most of them cannot be identified. This unidentified group of heterogeneous organic macromolecules is considered as humic substances. The role of humic substances in water chemistry and in aquatic toxicology is receiving increasing attention. The effects of DOC on the bioavailability of organic pollutants have been demonstrated in several studies. A decreased bioavailability has been demonstrated in most cases. Both the quantity and the quality of DOC are suggested determinants of this apparent ecotoxicological buffer of inland waters worldwide. In this study, the authors measured the bioaccumulation of benzo(a)pyrene (BaP) and dehydroabietic acid (DHAA) in Daphnia magna using a wide range of naturally occurring DOC levels. Another objective was to associate the reduced bioavailability with the chemical characteristics of water and DOC

  6. Asbestos and benzo[a]pyrene act synergistically to induce squamous metaplasia and incorporation of [3H]thymidine in hamster tracheal epithelium

    International Nuclear Information System (INIS)

    When exposed to either crocidolite asbestos (single 1-h exposure to 0.4 mg/ml medium) or the polycyclic aromatic hydrocarbon, benzo[a]pyrene (BaP) (less than or equal to 2.5 micrograms/ml medium, 1x weekly for 4 weeks), the epithelium of hamster tracheal explants exhibits insignificant amounts of squamous metaplasia, an atypical lesion, in comparison to amounts observed in untreated tissues. Incorporation of [3H]thymidine, an indication of DNA synthesis by epithelial cells, likewise is unchanged. However, the extent of squamous metaplasia and numbers of labeled basal and suprabasal cells are increased substantially when BaP and asbestos are added in combination. These results suggest an important mechanism of co-carcinogenesis involving chemical and physical carcinogens and support epidemiologic observations documenting an increased risk of bronchogenic carcinoma in asbestos workers who smoke

  7. Phosphatase activity in commercial spleen exonuclease decreases the recovery of benzo[a]pyrene and N-hydroxy-2-naphthylamine DNA adducts by 32P-postlabeling.

    Science.gov (United States)

    Adams, S P; Laws, G M; Selden, J R; Nichols, W W

    1994-05-15

    Spleen exonuclease, which degrades nucleic acids into single 3'-nucleotides, is used in the detection of DNA adducts by 32P-postlabeling. Contamination of the exonuclease with phosphatase activity can reduce the recovery of benzo[a]pyrene and N-hydroxy-2-naphthylamine DNA adducts by 32P-postlabeling. Four preparations of spleen exonuclease containing varying levels of phosphatase activity (2-naphthylamine DNA adducts. Surprisingly, recovery of these DNA adducts was nearly 10 times greater using nuclease P1 than when using 1-butanol extraction for adduct enrichment, since arylamine DNA adducts have previously been reported to be poorly detected by 32P-postlabeling after nuclease P1 treatment. Our data indicate that the hydrolysis of DNA by spleen exonuclease may be an important source of variability in both qualitative and quantitative analysis of adducts by 32P-postlabeling. PMID:8059938

  8. Synthesis and in vitro evaluation of (R), (S) and (R/S)-2-hexyne-1,4-diol, a natural product produced by fungus Clitocybe catinus, and related analogs as potential anticancer agents.

    Science.gov (United States)

    Princival, Iza Mirela R G; Ferreira, Jeiely G; Silva, Teresinha G; Aguiar, Jaciana S; Princival, Jefferson L

    2016-06-15

    The search for natural products and related analogs as potential anticancer agents has seen a significant growth worldwide. Since small sized propargylic diols can be found in nature and chemically synthesized, their evaluation against cancer cells has been of great interest, being a topic of relevance to be investigated. For this purpose, a scalable approach aiming at the synthesis of several propargylic diols and their bioactivity against seven tumor cell lines were evaluated. Interestingly, when the compound 1a, a natural product produced by fungus Clitocybe catinus, was tested in its racemic mixture a more effective activity was observed if compared when enantiopure R-1a or S-1a were tested separately. PMID:27142752

  9. DEET (N,N-diethyl-meta-toluamide)/PMD (para-menthane-3,8-diol) repellent-treated mesh increases Culicoides catches in light traps.

    Science.gov (United States)

    Murchie, A K; Clawson, S; Rea, I; Forsythe, I W N; Gordon, A W; Jess, S

    2016-09-01

    Biting midges (Culicoides spp.) are vectors of bluetongue and Schmallenberg viruses. Treatment of mesh barriers is a common method for preventing insect-vectored diseases and has been proposed as a means of limiting Culicoides ingression into buildings or livestock transporters. Assessments using animals are costly, logistically difficult and subject to ethical approval. Therefore, initial screening of test repellents/insecticides was made by applying treatments to mesh (2 mm) cages surrounding Onderstepoort light traps. Five commercial treatments were applied to cages as per manufacturers' application rates: control (water), bendiocarb, DEET/p-menthane-3,8-diol (PMD) repellent, Flygo (a terpenoid based repellent) and lambda-cyhalothrin. The experimental design was a 5 × 5 Latin square, replicated in time and repeated twice. Incongruously, the traps surrounded by DEET/PMD repellent-treated mesh caught three to four times more Obsoletus group Culicoides (the commonest midge group) than the other treatments. A proposed hypothesis is that Obsoletus group Culicoides are showing a dose response to DEET/PMD, being attracted at low concentrations and repelled at higher concentrations but that the strong light attraction from the Onderstepoort trap was sufficient to overcome close-range repellence. This study does not imply that DEET/PMD is an ineffective repellent for Culicoides midges in the presence of an animal but rather that caution should be applied to the interpretation of light trap bioassays. PMID:27179956

  10. Stereochemical effects in the gas-phase pinacol rearrangement. 2. Ring contraction versus methyl migration in cis- and trans-1,2-dimethylcyclohexane-1,2-diol

    International Nuclear Information System (INIS)

    The gas-phase pinacol rearrangement of cis- and trans-1,2-dimethylcyclohexane-1,2-diols, promoted by D3+, CH5+/C2H5+ and t-C4H9+ ions, was studied by mass spectrometric and radiolytic methods in the pressure range 0.5-760 Torr. When product isomerization is inhibited, by using N(CH3)3 as a trapping reagent at high pressure, mixtures of 2,2-dimethylcyclohexanone and 1-acetyl-1-methylcyclopentane were recovered from the reaction. In methane, the trend of the measured relative rates for ring contraction (k5), methyl or hydroxyl group migration (k6) versus the rearrangement rate of pincaol itself (k/sub p/), is k6(trans) ∼ k5(trans) ≥ k5(cis) > k6(cis) ≥ k/sub p/. No evidence for the formation of an intermediate carbenium ion was found. Stereochemical aspects of the mechanism are discussed and compared with solution data

  11. Acaricidal effects of Corymbia citriodora oil containing para-menthane-3,8-diol against nymphs of Ixodes ricinus (Acari: Ixodidae).

    Science.gov (United States)

    Elmhalli, Fawzeia H; Pålsson, Katinka; Orberg, Jan; Jaenson, Thomas G T

    2009-07-01

    The toxicity of para-menthane-3,8-diol (PMD), the main arthropod-repellent compound in the oil of the lemon eucalyptus, Corymbia citriodora, was evaluated against nymphs of Ixodes ricinus using five methods (A-E) of a contact toxicity bioassay. Mortality rates were estimated by recording numbers of dead nymphs at 30 min intervals during the first 5 h after the start of exposure and at longer intervals thereafter. The mortality rate increased with increasing concentration of PMD and duration of exposure with a distinct effect after 3.5 h. From the results obtained by methods A, C and E, the LC(50) range was 0.035-0.037 mg PMD/cm(2) and the LC(95) range was 0.095-0.097 mg PMD/cm(2) at 4 h of exposure; the LT(50) range was 2.1-2.8 h and the LT(95) range was 3.9-4.2 h at 0.1 mg PMD/cm(2). To determine the duration of toxic activity of PMD, different concentrations (0.002, 0.01, 0.1 mg PMD/cm(2)) were tested and mortality was recorded at each concentration after 1 h; thereafter new ticks were tested. This test revealed that the lethal activity of PMD remained for 24 h but appeared absent after 48 h. The overall results show that PMD is toxic to nymphs of I. ricinus and may be useful for tick control. PMID:19169833

  12. In silico stereo-electronic analysis of PMD (p-Menthane-3-8-Diol) and its derivatives for pharmacophore development may aid discovery of novel insect repellents.

    Science.gov (United States)

    Bhattacharjee, Apurba K

    2013-09-01

    PMD (p-menthane-3-8-diol) is an insect repellent that can be synthesized chemically or derived from a steam distillate residue of the leaves of lemon eucalyptus, Corymbia citriodora. It is one of the few natural product endorsed by the Center for Disease Control (USA) for topical application to protect against mosquitoes though it is not as effective as the common repellent DEET (N,N -diethyl-1,3-toluamide). However, DEET has several undesirable side effects and toxicity too. Thus, although PMDs are comparatively safer than DEET, no quantitative structure activity relationship (QSAR) and pharmacophore modeling studies have been reported in literature to improve efficacy and aid further development of more effective PMD analogues. In this study, we report results of quantum chemical analysis of stereoelectronic properties and pharmacophore modeling of PMD and eight of its synthetic derivatives to aid discovery and design of more effective PMD analogues. Stereo-electronic analysis indicates that lower aqueous stabilization (favorable lipophilicity) and larger separation of electrostatic potential energy together with a large localized negative electrostatic potential region by the oxygen atom play important roles for repellent activity. Consistent to these properties, the generated pharmacophore model of the PMDs showed two aliphatic hydrophobic and a hydrogen-bond donor features for potent activity. These results aided us to design more effective PMD repellents which are currently under further investigations. PMID:24010930

  13. MALDI-TOF MS Imaging evidences spatial differences in the degradation of solid polycaprolactone diol in water under aerobic and denitrifying conditions.

    Science.gov (United States)

    Rivas, Daniel; Ginebreda, Antoni; Pérez, Sandra; Quero, Carmen; Barceló, Damià

    2016-10-01

    Degradation of solid polymers in the aquatic environment encompasses a variety of biotic and abiotic processes giving rise to heterogeneous patterns across the surface of the material, which cannot be investigated using conventional Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) that only renders an "average" picture of the sample. In that context, MALDI-TOF MS Imaging (MALDI MSI) provides a rapid and efficient tool to study 2D spatial changes occurred in the chemical composition of the polymer surface. Commercial polycaprolactone diol (average molecular weight of 1250Da) was selected as test material because it had been previously known to be amenable to biological degradation. The test oligomer probe was incubated under aerobic and denitrifying conditions using synthetic water and denitrifying mixed liquor obtained from a wastewater treatment plant respectively. After ca. seven days of exposure the mass spectra obtained by MALDI MSI showed the occurrence of chemical modifications in the sample surface. Observed heterogeneity across the probe's surface indicated significant degradation and suggested the contribution of biotic processes. The results were investigated using different image processing tools. Major changes on the oligomer surface were observed when exposed to denitrifying conditions. PMID:27213667

  14. INFLUENCE OF 2-BUTYNE-1, 4-DIOL ON THE STRUCTURE AND PERFORMANCE OF THE Co-Ni ALLOY PLATED BY ELECTRODEPOSITION

    Institute of Scientific and Technical Information of China (English)

    S.L. Wang; L.L. Hong; W.W. Yu

    2008-01-01

    The effect of 2-butyne-1, 4-diol (BD) on the deposition behavior of the Co-Ni alloy was investigated by linear sweep voltammetry. The results showed that BD could prevent the deposition of the Co-Ni alloy. The elect of BD concentration in the sulfate plating bath, on the structure of the Co-Ni deposit was studied by energy dispersive x-ray spectroscopy, scanning electron microscope, and X-ray diffraction, respectively. As a result, BD could smoothen the deposit surface and decrease the diameter of the grain, but too much of BD was not good for the size of the grain. In general, a hexagonal close-packed (hcp) phase of the Co-Ni alloy, with a preferentially oriented (110) plane, was prepared by electrodeposition in the presence of BD. The Co-Ni alloy as a catalyst for the electro-oxidation of ethanol in alkaline medium was investigated by cyclic voltammetry. The deposit plated from the bath containing BD possessed better electro-oxidation of ethanol performance compared with that of the deposit plated from only the sulfate plating bath, but too much of BD was not beneficial for catalytic activity. The Co-Ni film was suitable as a magnetic recording material.

  15. Thermo-Responsive Polyurethane Hydrogels Based on Poly(ε-caprolactone Diol and Amphiphilic Polylactide-Poly(Ethylene Glycol Block Copolymers

    Directory of Open Access Journals (Sweden)

    Shan-hui Hsu

    2016-07-01

    Full Text Available Waterborne polyurethane (PU based on poly(ε-caprolactone (PCL diol and an amphiphilic polylactide-poly(ethylene glycol (PLA-PEG diblock copolymer was synthesized. The molar ratio of PCL/PLA-PEG was 9:1 with different PLA chain lengths. The PU nanoparticles were characterized by dynamic light scattering (DLS, small angle X-ray scattering (SAXS and rheological analysis. The water contact angle measurement, infrared spectroscopy, wide angle X-ray scattering (WAXS, thermal and mechanical analyses were conducted on PU films. Significant changes in physio-chemical properties were observed for PUs containing 10 mol % of amphiphilic blocks. The water contact angle was reduced to 12°–13°, and the degree of crystallinity was 5%–10%. The PU dispersions underwent sol-gel transition upon the temperature rise to 37 °C. The gelation time increased as the PLA chain length increased. In addition, the fractal dimension of each gel was close to that of a percolation cluster. Moreover, PU4 with a solid content of 26% could support the proliferation of human mesenchymal stem cells (hMSCs. Therefore, thermo-responsive hydrogels with tunable properties are promising injectable materials for cell or drug delivery.

  16. Optically active helical polyurethane-attapulgite composites: Effect of optical purity of S-1,1'-binaphthyl-2,2'-diol on infrared emissivity

    Energy Technology Data Exchange (ETDEWEB)

    Wang Zhiqiang [School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189 (China); Zhou Yuming, E-mail: ymzhou@seu.edu.cn [School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189 (China); Sun Yanqing; Mei Zhenyu; Miao Yuee [School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189 (China)

    2009-05-15

    Helical polyurethane-attapulgite (HPU-ATT) composites were prepared after the surface modification of the rod-like attapulgite (ATT). HPU-ATT composites based on S-1,1'-binaphthyl-2,2'-diol (S-BINOL) with different optical purity (O.P.) were characterized by Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). The results indicate that the helical polyurethane has been successfully grafted onto the surfaces of the modified ATT without destroying the original crystalline structure of ATT. The rod-like nanoparticles were confirmed by transmission electron microscopy (TEM). Infrared emissivity values of HPU-ATT composites have been investigated, and the results indicate that the optical purity of monomer plays a very important role in the infrared emissivity for HPU-ATT owing to the effect of helical conformation and interchain hydrogen bonds. Along with the increased optical purity of S-BINOL, the infrared emissivity of HPU-ATT is reduced evidently. Infrared emissivity value of HPU-ATT based on S-BINOL with 100% optical purity is the lowest one (0.431).

  17. Optically active helical polyurethane-attapulgite composites: Effect of optical purity of S-1,1'-binaphthyl-2,2'-diol on infrared emissivity

    International Nuclear Information System (INIS)

    Helical polyurethane-attapulgite (HPU-ATT) composites were prepared after the surface modification of the rod-like attapulgite (ATT). HPU-ATT composites based on S-1,1'-binaphthyl-2,2'-diol (S-BINOL) with different optical purity (O.P.) were characterized by Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). The results indicate that the helical polyurethane has been successfully grafted onto the surfaces of the modified ATT without destroying the original crystalline structure of ATT. The rod-like nanoparticles were confirmed by transmission electron microscopy (TEM). Infrared emissivity values of HPU-ATT composites have been investigated, and the results indicate that the optical purity of monomer plays a very important role in the infrared emissivity for HPU-ATT owing to the effect of helical conformation and interchain hydrogen bonds. Along with the increased optical purity of S-BINOL, the infrared emissivity of HPU-ATT is reduced evidently. Infrared emissivity value of HPU-ATT based on S-BINOL with 100% optical purity is the lowest one (0.431).

  18. 5-Androstene-3{beta},17{beta}-diol Promotes Recovery of Immature Hematopoietic Cells Following Myelosuppressive Radiation and Synergizes With Thrombopoietin

    Energy Technology Data Exchange (ETDEWEB)

    Aerts-Kaya, Fatima S.F.; Visser, Trudi P.; Arshad, Shazia [Department of Hematology, Erasmus University Medical Center, Rotterdam (Netherlands); Frincke, James; Stickney, Dwight R.; Reading, Chris L. [Harbor Therapeutics, Inc, San Diego, California (United States); Wagemaker, Gerard, E-mail: g.wagemaker@erasmusmc.nl [Department of Hematology, Erasmus University Medical Center, Rotterdam (Netherlands)

    2012-11-01

    Purpose: 5-Androstene-3{beta},17{beta}-diol (5-AED) stimulates recovery of hematopoiesis after exposure to radiation. To elucidate its cellular targets, the effects of 5-AED alone and in combination with (pegylated) granulocyte colony-stimulating factor and thrombopoietin (TPO) on immature hematopoietic progenitor cells were evaluated following total body irradiation. Methods and Materials: BALB/c mice were exposed to radiation delivered as a single or as a fractionated dose, and recovery of bone marrow progenitors and peripheral blood parameters was assessed. Results: BALB/c mice treated with 5-AED displayed accelerated multilineage blood cell recovery and elevated bone marrow (BM) cellularity and numbers of progenitor cells. The spleen colony-forming unit (CFU-S) assay, representing the life-saving short-term repopulating cells in BM of irradiated donor mice revealed that combined treatment with 5-AED plus TPO resulted in a 20.1-fold increase in CFU-S relative to that of placebo controls, and a 3.7 and 3.1-fold increase in comparison to 5-AED and TPO, whereas no effect was seen of Peg-G-CSF with or without 5-AED. Contrary to TPO, 5-AED also stimulated reconstitution of the more immature marrow repopulating (MRA) cells. Conclusions: 5-AED potently counteracts the hematopoietic effects of radiation-induced myelosuppression and promotes multilineage reconstitution by stimulating immature bone marrow cells in a pattern distinct from, but synergistic with TPO.

  19. Inhibitory effect of sesquiterpene lactones and the sesquiterpene alcohol aromadendrane-4β,10α-diol on memory impairment in a mouse model of Alzheimer.

    Science.gov (United States)

    Amoah, Solomon K S; Dalla Vecchia, Maria Tereza; Pedrini, Beatriz; Carnhelutti, Gabriela Lazzarotto; Gonçalves, Ana Elisa; Dos Santos, Diogo Adolfo; Biavatti, Maique W; de Souza, Márcia Maria

    2015-12-15

    Alzheimer's disease (AD), a progressive neurodegenerative disorder of the aged brain with no known cause or cures, has become a major medical and social problem for industrialized countries. Cerebral deposition of amyloid-β peptide (Aβ) is a critical feature of AD. The use of medicinal plants as an alternative form of prevention, or even as a possible treatment of AD, is therefore interesting areas of research. Sesquiterpene lactones and a sesquiterpene alcohol are compounds found in H. brasiliense that have several anti-oxidative and anti-inflammatory effects. In the present study, we investigated whether these compounds have neuroprotective effects in an amyloid-β peptide-induced Alzheimer's disease mouse model. Mice were injected with Aβ1-42 peptide intracerebroventricularly and were subsequently injected (i.c.v.) with 1µg/site of IGM-A (15-acetoxy-isogermafurenolide), IGM-H (15-hydroxy-isogermafurenolide), PDA (Podoandin), EHP (1,2-epoxy-10α-hydroxy-podoandin), HDS (13-hydroxy-8,9-dehydroshizukanolide), and ARD (aromadendrane-4β,10α-diol). Seven days after treatments the animals had their memory tested in the inhibitory avoidance. After the behavioral testing of animals the brains were removed and subjected to biochemical tests for oxidative stress. The results showed that ARD, HDS and PDA significantly ameliorated the Aβ1-42 peptide-induced memory impairment in the passive avoidance task (Panimals induced peptide amyloid and may be potential candidates for Alzheimer's disease therapy. PMID:26593432

  20. The solid-matrix phosphorescence of (±)-anti-dibenzo[a,l]pyrene diol epoxide-DNA adducts and benzo[e]pyrene

    International Nuclear Information System (INIS)

    New solid-matrix phosphorescence (SMP) methods for (±)-anti-DB[a,l]PDE-DNA adducts and B[e]P were developed. The methods can be used to detect and characterize (±)-anti-DB[a,l]PDE-DNA adducts and B[e]P by employing SMP spectra, intensities, and lifetimes acquired with the heavy-atom salt, TlNO3, on Whatman 1PS paper. With the SMP data, a number of photophysical parameters were calculated such as biexponential SMP decay curves, pre-exponential factors, and fractional contribution to SMP decay curves. The SMP results were compared with earlier SMP data for (±)-anti-BPDE-DNA adducts and tetrol I-1. The SMP results show that small molecular-weight compounds like B[e]P can be readily detected and characterized by SMP. For example, the limit of detection for B[e]P was 0.60 pmol. Comparison of the SMP properties of the (±)-anti-DB[a,l]PDE-DNA adducts with earlier SMP data for the (±)-anti-BPDE-DNA adducts showed major differences in the SMP spectra, intensities, and lifetimes. The methods developed are important for the comparison of the SMP properties of different diol epoxides of PAH bonded to DNA

  1. 5-Androstene-3β,17β-diol Promotes Recovery of Immature Hematopoietic Cells Following Myelosuppressive Radiation and Synergizes With Thrombopoietin

    International Nuclear Information System (INIS)

    Purpose: 5-Androstene-3β,17β-diol (5-AED) stimulates recovery of hematopoiesis after exposure to radiation. To elucidate its cellular targets, the effects of 5-AED alone and in combination with (pegylated) granulocyte colony-stimulating factor and thrombopoietin (TPO) on immature hematopoietic progenitor cells were evaluated following total body irradiation. Methods and Materials: BALB/c mice were exposed to radiation delivered as a single or as a fractionated dose, and recovery of bone marrow progenitors and peripheral blood parameters was assessed. Results: BALB/c mice treated with 5-AED displayed accelerated multilineage blood cell recovery and elevated bone marrow (BM) cellularity and numbers of progenitor cells. The spleen colony-forming unit (CFU-S) assay, representing the life-saving short-term repopulating cells in BM of irradiated donor mice revealed that combined treatment with 5-AED plus TPO resulted in a 20.1-fold increase in CFU-S relative to that of placebo controls, and a 3.7 and 3.1-fold increase in comparison to 5-AED and TPO, whereas no effect was seen of Peg-G-CSF with or without 5-AED. Contrary to TPO, 5-AED also stimulated reconstitution of the more immature marrow repopulating (MRA) cells. Conclusions: 5-AED potently counteracts the hematopoietic effects of radiation-induced myelosuppression and promotes multilineage reconstitution by stimulating immature bone marrow cells in a pattern distinct from, but synergistic with TPO.

  2. Diastereo- and Enantioselective Iridium Catalyzed Coupling of Vinyl Aziridines with Alcohols: Site-Selective Modification of Unprotected Diols and Synthesis of Substituted Piperidines.

    Science.gov (United States)

    Wang, Gang; Franke, Jana; Ngo, Chinh Q; Krische, Michael J

    2015-06-24

    The chiral cyclometalated π-allyliridium ortho-C,O-benzoate complex (R)-Ir-VIb derived from [Ir(cod)Cl]2, allyl acetate, 4-cyano-3-nitro-benzoic acid, and (R)-MeO-BIPHEP catalyzes the coupling of N-(p-nitrophenylsulfonyl) protected vinyl aziridine 3a with primary alcohols 1a-1l to furnish branched products of C-C bond formation 4a-4l with good levels of anti-diastereo- and enantioselectivity. In the presence of 2-propanol, but under otherwise identical conditions, vinyl aziridine 3a and aldehydes 2a-2l engage in reductive coupling to furnish an equivalent set of adducts 4a-4l with roughly equivalent levels of anti-diastereo- and enantioselectivity. Using enantiomeric iridium catalysts, vinyl aziridine 3a reacts with unprotected chiral 1,3-diols 1m-1o in a site-selective manner to deliver the diastereomeric products of C-allylation syn-4m, -4n, -4o and anti-4m, -4n, -4o, respectively, with good isolated yields and excellent levels of catalyst-directed diastereoselectivity. These adducts were directly converted to the diastereomeric 2,4,5-trisubstituted piperidines syn-5m, -5n, -5o and anti-5m, -5n, -5o. PMID:26074091

  3. Treatment of a Human Papillomavirus Type 31b-Positive Cell Line with Benzo[a]Pyrene Increases Viral Titer through Activation of the Erk1/2 Signaling Pathway▿

    OpenAIRE

    Bowser, Brian S; Alam, Samina; Meyers, Craig

    2011-01-01

    Numerous epidemiological studies have implicated cigarette smoking as a cofactor in the progression to cervical cancer. Tobacco-associated hydrocarbons have been found in cervical mucus, suggesting a possible interaction with human papillomavirus (HPV)-infected cells. The polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP) is a major component of cigarette smoke condensate that has received significant attention due to its ability to induce carcinogenesis. We have previously demonstrated by ...

  4. Enhanced binding capacity of boronate affinity adsorbent via surface modification of silica by combination of atom transfer radical polymerization and chain-end functionalization for high-efficiency enrichment of cis-diol molecules

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Wei; He, Maofang; Wang, Chaozhan; Wei, Yinmao, E-mail: ymwei@nwu.edu.cn

    2015-07-30

    Boronate affinity materials have been widely used for specific separation and preconcentration of cis-diol molecules, but most do not have sufficient capacity due to limited binding sites on the material surface. In this work, we prepared a phenylboronic acid-functionalized adsorbent with a high binding capacity via the combination of surface-initiated atom transfer radical polymerization (SI-ATRP) and chain-end functionalization. With this method, the terminal chlorides of the polymer chains were used fully, and the proposed adsorbent contains dense boronic acid polymers chain with boronic acid on the chain end. Consequently, the proposed adsorbent possesses excellent selectivity and a high binding capacity of 513.6 μmol g{sup −1} for catechol and 736.8 μmol g{sup −1} for fructose, which are much higher than those of other reported adsorbents. The dispersed solid-phase extraction (dSPE) based on the prepared adsorbent was used for extraction of three cis-diol drugs (i.e., epinephrine, isoprenaline and caffeic acid isopropyl ester) from plasma; the eluates were analyzed by HPLC-UV. The reduced amount of adsorbent (i.e., 2.0 mg) could still eliminate interferences efficiently and yielded a recovery range of 85.6–101.1% with relative standard deviations ranging from 2.5 to 9.7% (n = 5). The results indicated that the proposed strategy could serve as a promising alternative to increase the density of surface functional groups on the adsorbent; thus, the prepared adsorbent has the potential to effectively enrich cis-diol substances in real samples. - Highlights: • Boronate adsorbent is prepared via ATRP and chain-end functionalization. • The adsorbent has quite high binding capacity for cis-diols. • Binding capacity is easily manipulated by ATRP condition. • Chain-end functionalization can improve binding capacity significantly. • Reduced adsorbent is consumed in dispersed solid-phase extraction of cis-diols.

  5. Enhanced binding capacity of boronate affinity adsorbent via surface modification of silica by combination of atom transfer radical polymerization and chain-end functionalization for high-efficiency enrichment of cis-diol molecules

    International Nuclear Information System (INIS)

    Boronate affinity materials have been widely used for specific separation and preconcentration of cis-diol molecules, but most do not have sufficient capacity due to limited binding sites on the material surface. In this work, we prepared a phenylboronic acid-functionalized adsorbent with a high binding capacity via the combination of surface-initiated atom transfer radical polymerization (SI-ATRP) and chain-end functionalization. With this method, the terminal chlorides of the polymer chains were used fully, and the proposed adsorbent contains dense boronic acid polymers chain with boronic acid on the chain end. Consequently, the proposed adsorbent possesses excellent selectivity and a high binding capacity of 513.6 μmol g−1 for catechol and 736.8 μmol g−1 for fructose, which are much higher than those of other reported adsorbents. The dispersed solid-phase extraction (dSPE) based on the prepared adsorbent was used for extraction of three cis-diol drugs (i.e., epinephrine, isoprenaline and caffeic acid isopropyl ester) from plasma; the eluates were analyzed by HPLC-UV. The reduced amount of adsorbent (i.e., 2.0 mg) could still eliminate interferences efficiently and yielded a recovery range of 85.6–101.1% with relative standard deviations ranging from 2.5 to 9.7% (n = 5). The results indicated that the proposed strategy could serve as a promising alternative to increase the density of surface functional groups on the adsorbent; thus, the prepared adsorbent has the potential to effectively enrich cis-diol substances in real samples. - Highlights: • Boronate adsorbent is prepared via ATRP and chain-end functionalization. • The adsorbent has quite high binding capacity for cis-diols. • Binding capacity is easily manipulated by ATRP condition. • Chain-end functionalization can improve binding capacity significantly. • Reduced adsorbent is consumed in dispersed solid-phase extraction of cis-diols

  6. Polycyclic aromatic hydrocarbons as skin carcinogens: Comparison of benzo[a]pyrene, dibenzo[def,p]chrysene and three environmental mixtures in the FVB/N mouse

    International Nuclear Information System (INIS)

    The polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BaP), was compared to dibenzo[def,p]chrysene (DBC) and combinations of three environmental PAH mixtures (coal tar, diesel particulate and cigarette smoke condensate) using a two stage, FVB/N mouse skin tumor model. DBC (4 nmol) was most potent, reaching 100% tumor incidence with a shorter latency to tumor formation, less than 20 weeks of 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion compared to all other treatments. Multiplicity was 4 times greater than BaP (400 nmol). Both PAHs produced primarily papillomas followed by squamous cell carcinoma and carcinoma in situ. Diesel particulate extract (1 mg SRM 1650b; mix 1) did not differ from toluene controls and failed to elicit a carcinogenic response. Addition of coal tar extract (1 mg SRM 1597a; mix 2) produced a response similar to BaP. Further addition of 2 mg of cigarette smoke condensate (mix 3) did not alter the response with mix 2. PAH-DNA adducts measured in epidermis 12 h post initiation and analyzed by 32P post‐labeling, did not correlate with tumor incidence. PAH‐dependent alteration in transcriptome of skin 12 h post initiation was assessed by microarray. Principal component analysis (sum of all treatments) of the 922 significantly altered genes (p < 0.05), showed DBC and BaP to cluster distinct from PAH mixtures and each other. BaP and mixtures up-regulated phase 1 and phase 2 metabolizing enzymes while DBC did not. The carcinogenicity with DBC and two of the mixtures was much greater than would be predicted based on published Relative Potency Factors (RPFs). -- Highlights: ► Dibenzo[def,p]chrysene (DBC), 3 PAH mixtures, benzo[a]pyrene (BaP) were compared. ► DBC and 2 PAH mixtures were more potent than Relative Potency Factor estimates. ► Transcriptome profiles 12 hours post initiation were analyzed by microarray. ► Principle components analysis of alterations revealed treatment-based clustering. ► DBC gave a unique pattern of

  7. Benzo(a)pyrene inhibits migration and invasion of extravillous trophoblast HTR-8/SVneo cells via activation of the ERK and JNK pathway.

    Science.gov (United States)

    Liu, Liyuan; Wang, Yingxiong; Shen, Cha; He, Junlin; Liu, Xueqing; Ding, Yubin; Gao, Rufei; Chen, Xuemei

    2016-07-01

    Benzo(a)pyrene (BaP) is a persistent organic pollutant (POP) that is a serious threat to human health. Numerous studies have shown that BaP causes adverse effects in pregnancy, but the mechanism remains unclear. The moderate invasion of trophoblast cells into the endometrium is an important factor during successful embryo implantation. The aim of this study was to investigate the effect and mechanism of BaP on the invasion and migration of trophoblast cells. HTR-8/SVneo cells were treated with different concentrations (1, 5, 10, 25, 50 and 100 μM) of BaP. The invasion and migration of HTR-8/SVneo cells were observed after BaP treatment. The protein levels related to migration and invasion was detected by Western blot. The results confirmed that BaP inhibits the migration and invasion of extravillous trophoblast HTR-8/SVneo cells. Further investigations indicated that the protein levels of MMP-2, MMP-9 and E-cadherin in HTR-8/SVneo cells were changed by BaP treatment. Moreover, the data demonstrated that BaP activated the MAPK signaling pathway. Pretreatment with specific inhibitors of MAPK rescued BaP-induced change in the migration and invasion of HTR-8/SVneo cells. Taken together, our results indicated that BaP inhibits invasion and the migration of HTR-8/SVneo cells, which might cause a failure in early pregnancy. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26359795

  8. MicroRNA Responses to the Genotoxic Carcinogens Aflatoxin B1 and Benzo[a]pyrene in Human HepaRG Cells.

    Science.gov (United States)

    Marrone, April K; Tryndyak, Volodymyr; Beland, Frederick A; Pogribny, Igor P

    2016-02-01

    Recent advances in toxicogenomics present an opportunity to develop new in vitro testing methodologies to identify human carcinogens. We have investigated microRNA expression responses to the treatment of human liver HepaRG cells with the human genotoxic carcinogens aflatoxin B1 (AFB1) and benzo[a]pyrene (B[a]P), and the structurally similar compounds aflatoxin B2 (AFB2) and benzo[e]pyrene (B[e]P) that exhibit minimal carcinogenic potential. We demonstrate that treatment of HepaRG cells with AFB1 or B[a]P resulted in specific changes in the expression of miRNAs as compared with their non-carcinogenic analogues, particularly in a marked over-expression of miR-410. An additional novel finding is the dose- and time-dependent inhibition of miR-122 in AFB1-treated HepaRG cells. Mechanistically, the AFB1-induced down-regulation of miR-122 was attributed to inhibition of the HNF4A/miR-122 regulatory pathway. These results demonstrate that HepaRG cells can be used to investigate miRNA responses to xenobiotic exposure, and illustrate the existence of early non-genotoxic events, in addition to a well-established genotoxic mode of action changes, in the mechanism of AFB1 and B[a]P carcinogenicity. PMID:26609139

  9. Ontogenetic variation in rat liver, lung and kidney monooxygenase induction by low doses of benzo(A)pyrene and cigarette-smoke condensate

    Energy Technology Data Exchange (ETDEWEB)

    van Cantfort, J.; Gielen, J.E.

    1981-12-01

    The specific lung-AHH induction, which we previously observed after the inhalation of cigarette smoke, is not due to the route followed by the inhaled smoke, for the same phenomenon occurs after i.p. injection of either cigarette smoke condensate (CSC) or benzo(a)pyrene in low doses. In this respect lung AHH behaves completely differently from the liver and kidney enzyme, in which organs, basal AHH activity (which is low in the foetus) increases rapidly after birth to reach the adult level 2 months later, and is only inducible by CSC and low doses of BP in unweaned rats. In the lung, the basal AHH activity (low in the foetus) increases abruptly at birth, peaks in 5-day-old rats and then decreases slightly. Contrary to enzyme activity in other tissues, lung AHH cannot be induced in unweaned young animals. The enzyme subsequently becomes sensitive to inducing agents and is highly inducible in 90-day-old rats. Similar behaviour occurs in 2 other enzymes linked to cytochrome P1450: ethoxycoumarin deethylase and ethoxyresorufin deethylase. The results could be related to the particular susceptibility of the lung to develop cancer after the inhalation of cigarette smoke.

  10. Differences in the covalent binding of benzo(a)pyrene, safrole, 1'-hydroxysafrole, and 4-aminobiphenyl to DNA of pregnant and non-pregnant mice

    International Nuclear Information System (INIS)

    The effects of pregnancy on the covalent binding of several carcinogens to DNA were investigated in mice. Non-pregnant or timed-pregnant (18th day of gestation) ICR mice of similar age were treated with benzo(a)pyrene (BP, 200 μmol/kg), safrole (600 μmol/kg), 1'-hydroxysafrole (400 μmol/kg), 4-aminobiphenyl (4-ABP, 800 μmol/kg) or trioctanoin (4 ml/kg) per os. Tissue DNA adduct levels at 24 h after carcinogen treatment were analyzed via a 32P-postabeling assay. Pregnancy lowered the binding of the ultimate carcinogenic metalolite of BP, 7β, 8α-dihydroxy-9, 10α-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDE I), to liver and lung DNA by 29-41%, but not the binding of other metabolites. The binding of safrole and its proximate carcinogen, 1'-hydroxysafrole, to liver and kidney DNA was increased 2.3-3.5 fold. Pregnancy decreased the binding of 4-ABP to liver DNA by approx. 18% but increased its binding to kidney DNA by 67%. The results suggest that exposure to some genotoxic compounds especially those requiring conjugation reactions for metabolic activation, may be more hazardous during pregnancy than in the non-pregnant state (author)

  11. Preliminary evidence of the role of hydrogen peroxide in the degradation of benzo[a]pyrene by a non-white rot fungus Fusarium solani

    Energy Technology Data Exchange (ETDEWEB)

    Veignie, Etienne; Rafin, Catherine; Woisel, Patrice; Cazier, Fabrice

    2004-05-01

    In order to study the enzymatic mechanisms involved in the successive steps of BaP degradation by a Deuteromycete fungus Fusarium solani, we developed an indirect approach by using inhibitors of enzymes. We used either specific inhibitors of peroxidases (i.e. salicylhydroxamic acid) and of cytochrome P-450 (i.e. piperonyl butoxyde) or inhibitors of both enzymes (i.e. potassium cyanide). Surprisingly, no expected decrease of BaP degradation was observed with most inhibitors tested. On the contrary, more BaP was degraded. Only butylated hydroxytoluene, which acts as a free radical scavenger, inhibited BaP degradation. The inhibition of these enzymes, which use H{sub 2}O{sub 2} as a cosubstrat, might have resulted in an increase of hydrogen peroxide availability in the fungal cultures. This enhancement could induce formation of reactive oxygen species (ROS) which might be the agents that initiate benzo[a]pyrene oxidation. This study proposed a hypothetic alternative metabolic pathway involved in PAH metabolism by Fusarium solani. - An alternative metabolic pathway was demonstrated.

  12. Humic acid-bonded silica as a novel sorbent for solid-phase extraction of benzo[a]pyrene in edible oils

    International Nuclear Information System (INIS)

    A novel solid-phase extraction (SPE) sorbent, humic acid-bonded silica (HAS), was prepared. Humic acids (HAs) were grafted onto silica matrices via an amide linkage between humyl chloride and the amido terminus of 3-aminopropyltrimethoxysilane (APTS)-silica gel. The resulting material was characterized by Fourier transform infrared spectrometer, elemental analysis, and nitrogen adsorption analysis. This sorbent exhibits an excellent adsorption capacity for some electron-abundant analytes owing to its peculiar structure. In this paper, we choose benzo[a]pyrene (BaP) in oil as a probe to validate the adsorption capacity of the material. Thus a fast, cheap and simple SPE method with humic acid-bonded silica cartridge for edible oil clean-up, followed by high-performance liquid chromatography (HPLC) with fluorescence detection was established. The effects of experimental variables, such as washing and elution solvents, and the amount of sorbents have been studied. The recoveries of BaP in edible oils spiked at 0.2-100 μg kg-1 were in the range of 78.8-102.7% with relative standard deviations ranging between 1.3 and 9.3%; the limit of detection was -0.06 μg kg-1

  13. The combined toxicity of dibutyl phthalate and benzo(a)pyrene on the reproductive system of male Sprague Dawley rats in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Chen Xuemei [Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016 (China); An Hui; Ao Lin; Sun Lei; Liu Wenbin; Zhou Ziyuan [Department of Hygenic Toxicology, College of Military Preventive Medicine, Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Third Military Medical University, Chongqing 400038 (China); Wang Yingxiong, E-mail: wyx61221@yahoo.com.cn [Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016 (China); Cao Jia, E-mail: caojia1962@126.com [Department of Hygenic Toxicology, College of Military Preventive Medicine, Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Third Military Medical University, Chongqing 400038 (China)

    2011-02-15

    Our previous studies revealed more than 100 pollutants, most of which were endocrine disruptors (EDs) in two Chinese rivers, the Jialing and the Yangtze near Chongqing. Most EDs, such as dibutyl phthalate (DBP) and benzo(a)pyrene (BaP), are known to act individually as reproductive toxicants. However, little is known about the combined toxicity of DBP and BaP. In the current study, male Sprague Dawley rats were subchronically exposed to single doses of DBP (250 mg/kg), single doses of BaP (5 mg/kg) and combined doses of DBP and BaP. Significant adverse effects were observed on the reproductive system, including decreased sperm count, increased production of abnormal sperm, changes in serum testosterone levels and irregular arrangements of the seminiferous epithelium. Biochemical analyses showed that the activities of superoxide dismutase and glutathione peroxidase decreased after exposure to these EDs. Therefore, our data suggest that exposure to DBP and BaP, in either separate or combined doses, can affect the reproductive system of male rats adversely via oxidative stress-related mechanisms. No significant additive effect was observed after combined exposure. These results indicate that exposure to mixtures of EDs have unexpected and elusive effects. Our findings provide preliminary but important data for assessing water safety in China.

  14. Measurement of human CYP1A2 induction by inhalation exposure to benzo(a)pyrene based on in vivo isotope breath method.

    Science.gov (United States)

    Duan, Xiaoli; Shen, Guofeng; Yang, Hongbiao; Lambert, George; Wei, Fusheng; Zhang, Junfeng Jim

    2016-01-01

    Cytochrome P450 1A2 (CYP1A2) is an enzyme involved in the metabolic activation of certain carcinogens, and inducible by toxic substrates. To date, few studies have investigated in vivo CYP1A2 induction in humans and its relationship to polycylic aromatic hydrocarbons (PAHs) like benzo(a)pyrene (BaP). Non-smoking healthy male coke-oven workers (n = 30) were recruited as 'exposure' group, and non-smoking healthy office workers in the same city (n = 10) were selected as 'control' group, to test whether high inhalation exposure to PAHs can induce CYP1A2 activity in human livers. Significantly higher inhalation exposure of PAHs were found among the exposure group compared to the control. Inhalation BaP exposure concentration in the exposure group was more than 30 times higher than the control group (p < 0.001). However, the exposure group did not exhale significant higher levels of (13)CO2/(12)CO2 in breath samples (p = 0.81), and no significant relationship was found between the inhaled BaP concentration and the (13)CO2/(12)CO2 ratio (p = 0.91). A significant association was found between the (13)CO2/(12)CO2 exhalation and dietary BaP intake level. Hepatic CYP1A2 activity/induction level was not effected by inhaled BaP but was altered by ingestion of BaP. PMID:26552516

  15. Oral exposure to environmental pollutant benzo[a]pyrene impacts the intestinal epithelium and induces gut microbial shifts in murine model

    Science.gov (United States)

    Ribière, Céline; Peyret, Pierre; Parisot, Nicolas; Darcha, Claude; Déchelotte, Pierre J.; Barnich, Nicolas; Peyretaillade, Eric; Boucher, Delphine

    2016-01-01

    Gut microbiota dysbiosis are associated with a wide range of human diseases, including inflammatory bowel diseases. The physiopathology of these diseases has multifactorial aetiology in which environmental factors, particularly pollution could play a crucial role. Among the different pollutants listed, Polycyclic Aromatic Hydrocarbons (PAHs) are subject to increased monitoring due to their wide distribution and high toxicity on Humans. Here, we used 16S rRNA gene sequencing to investigate the impact of benzo[a]pyrene (BaP, most toxic PAH) oral exposure on the faecal and intestinal mucosa-associated bacteria in C57BL/6 mice. Intestinal inflammation was also evaluated by histological observations. BaP oral exposure significantly altered the composition and the abundance of the gut microbiota and led to moderate inflammation in ileal and colonic mucosa. More severe lesions were observed in ileal segment. Shifts in gut microbiota associated with moderate inflammatory signs in intestinal mucosa would suggest the establishment of a pro-inflammatory intestinal environment following BaP oral exposure. Therefore, under conditions of genetic susceptibility and in association with other environmental factors, exposure to this pollutant could trigger and/or accelerate the development of inflammatory pathologies. PMID:27503127

  16. Effects of polycyclic aromatic hydrocarbons (PAHs) on an aquatic ecosystem: acute toxicity and community-level toxic impact tests of benzo[a]pyrene using lake zooplankton community.

    Science.gov (United States)

    Ikenaka, Yoshinori; Sakamoto, Masaki; Nagata, Takamaru; Takahashi, Hirokazu; Miyabara, Yuichi; Hanazato, Takayuki; Ishizuka, Mayumi; Isobe, Tomohiko; Kim, Jun-Woo; Chang, Kwang-Hyeon

    2013-02-01

    We estimated acute toxicity of benzo[a]pyrene (B[a]P) using two cladoceran species, Ceriodaphnia reticulata and Daphnia magna, and also analyzed its impact on zooplankton community throughout an exposure experiment using small-scale mesocosms. LC(50) of B[a]P for C. reticulata and D. magna was 4.3 and 4.7 µg/l, respectively. However, individuals fed with Chlorella showed higher LC(50), 6.1 µg/l for C. reticulata and 8.0 µg/l for D. magna. In the exposure experiment, we examined the impact of B[a]P on zooplankton community using conceivable concentrations in the environment (5 and 10 µg/l) using typical zooplankton community in eutrophicated systems. Despite the residence time of B[a]P in the water column was short as recovery pattern was different among cladocerans and rotifers. Consequently, B[a]P showed insecticide-like impacts, suppressing cladoceran populations and inducing the dominance of rotifers particularly under high concentration (10 µg/l). Results have suggested that, even such short duration of B[a]P in the water body can have impact on zooplankton abundance and community structure. Since B[a]P easily precipitate to the bottom and rapidly disappears from the water body, careful monitoring and further assessment of the potential toxicity of polycyclic aromatic hydrocarbons are necessary. PMID:23358147

  17. Modulation of benzo[a]pyrene induced neurotoxicity in female mice actively immunized with a B[a]P-diphtheria toxoid conjugate.

    Science.gov (United States)

    Schellenberger, Mario T; Grova, Nathalie; Farinelle, Sophie; Willième, Stéphanie; Schroeder, Henri; Muller, Claude P

    2013-09-01

    Benzo[a]pyrene (B[a]P) is a small molecular weight carcinogen and the prototype of polycyclic aromatic hydrocarbons (PAHs). While these compounds are primarily known for their carcinogenicity, B[a]P and its metabolites are also neurotoxic for mammalian species. To develop a prophylactic immune strategy against detrimental effects of B[a]P, female Balb/c mice immunized with a B[a]P-diphtheria toxoid (B[a]P-DT) conjugate vaccine were sub-acutely exposed to 2mg/kg B[a]P and behavioral performances were monitored in tests related to learning and memory, anxiety and motor coordination. mRNA expression of the NMDA receptor (NR1, 2A and 2B subunits) involved in the above behavioral functions was measured in 5 brain regions. B[a]P induced NMDA1 expression in three (hippocampus, amygdala and cerebellum) of five brain regions investigated, and modulated NMDA2 in two of the five brain regions (frontal cortex and cerebellum). Each one of these B[a]P-effects was reversed in mice that were immunized against this PAH, with measurable consequences on behavior such as anxiety, short term learning and memory. Thus active immunization against B[a]P with a B[a]P-DT conjugate vaccine had a protective effect and attenuated the pharmacological and neurotoxic effects even of high concentrations of B[a]P. PMID:23684556

  18. In vitro and in vivo percutaneous absorption of benzo[a]pyrene from petroleum crude-fortified soil in the rat

    International Nuclear Information System (INIS)

    Concern regarding dermal exposure to soils contaminated with potentially toxic materials such as dioxins, pesticides, heavy metals, polynuclear aromatics (PNA) and petroleum products containing PNA, has prompted government and private sectors to examine and formulate dermal risk assessment methodologies for contaminated soils. In the absence of experimentally determined percutaneous absorption values, many risk assessment schemes substitute available animal toxicology data on the pure contaminant, estimate dermal penetration of pure contaminant based on physicochemical models or, in the extreme, assume 100% bioavailability of the contaminant from soil. Risk assessment based on these approaches is likely to result in an overestimate of dermal bioavailability of contaminants from soil, particularly for the water insoluble lipophilic compounds found in petroleum products. The authors have performed dermal bioavailability studies on a variety of lipophilic materials and special emphasis has been placed on the development and implementation of a modified in vitro technique for evaluating the percutaneous absorption of PNA and PNA mixtures. In the present paper, they apply the modified in vitro technique to evaluate the percutaneous absorption of [3H-labelled] benzo[a]pyrene (BaP) in petroleum crude oil sorbed on soil and compare the results with those for the percutaneous absorption of BaP from crude oil alone. Results of the in vitro experiments are compared with findings from parallel in vivo experiments

  19. Degradation of 14C labelled Benzo[a]pyrene by a PAH-adapted mixed bacterial culture in the presence of an alkylpolyglycoside-surfactant

    International Nuclear Information System (INIS)

    The biodegradation of the five ring PAH benzo[a]pyrene (BaP) is assumed to be limited by the low water solubility of this compound. A mixed culture of microorganisms - isolated from a PAH-contaminated soil - was able to degrade 14C labelled BaP in mineral medium by co-metabolism with phenanthrene, fluoranthene, anthracene and pyrene as sources of carbon and energy. The mineralisation of these compounds to low levels resulted in an inhibition of the degradation of BaP. After the new addition of the four PAH compounds to the culture medium the mineralisation of BaP started again. A non-ionic surfactant of the alkylpolyglycoside type (Plantacare 2000 UP) increased the concentration of BaP in the culture medium because of solubilization. At high Plantacare concentrations, the degradation of BaP was completely inhibited above the critical micelle concentration (cms). The degradation of the three and four ring PAHs was also inhibited. If the surfactant was metabolised to concentrations below the cmc, an increase of mineralisation of BaP could occur up to 24% in 384 days. (orig.)

  20. High Conservation in Transcriptomic and Proteomic Response of White Sturgeon to Equipotent Concentrations of 2,3,7,8-TCDD, PCB 77, and Benzo[a]pyrene.

    Science.gov (United States)

    Doering, Jon A; Tang, Song; Peng, Hui; Eisner, Bryanna K; Sun, Jianxian; Giesy, John P; Wiseman, Steve; Hecker, Markus

    2016-05-01

    Adverse effects associated with exposure to dioxin-like compounds (DLCs) are mediated primarily through activation of the aryl hydrocarbon receptor (AHR). However, little is known about the cascades of events that link activation of the AHR to apical adverse effects. Therefore, this study used high-throughput, next-generation molecular tools to investigate similarities and differences in whole transcriptome and whole proteome responses to equipotent concentrations of three agonists of the AHR, 2,3,7,8-TCDD, PCB 77, and benzo[a]pyrene, in livers of a nonmodel fish, the white sturgeon (Acipenser transmontanus). A total of 926 and 658 unique transcripts were up- and down-regulated, respectively, by one or more of the three chemicals. Of the transcripts shared by responses to all three chemicals, 85% of up-regulated transcripts and 75% of down-regulated transcripts had the same magnitude of response. A total of 290 and 110 unique proteins were up- and down-regulated, respectively, by one or more of the three chemicals. Of the proteins shared by responses to all three chemicals, 70% of up-regulated proteins and 48% of down-regulated proteins had the same magnitude of response. Among treatments there was 68% similarity between the global transcriptome and global proteome. Pathway analysis revealed that perturbed physiological processes were indistinguishable between equipotent concentrations of the three chemicals. The results of this study contribute toward more completely describing adverse outcome pathways associated with activation of the AHR. PMID:27070345

  1. Analysis of benzo[a]pyrene in vegetable oils using molecularly imprinted solid phase extraction (MISPE) coupled with enzyme-linked immunosorbent assay (ELISA).

    Science.gov (United States)

    Pschenitza, Michael; Hackenberg, Rudolf; Niessner, Reinhard; Knopp, Dietmar

    2014-01-01

    This paper describes the development of a molecularly imprinted polymer-based solid phase extraction (MISPE) method coupled with enzyme-linked immunosorbent assay (ELISA) for determination of the PAH benzo[a]pyrene (B[a]P) in vegetable oils. Different molecularly imprinted polymers (MIPs) were prepared using non-covalent 4-vinylpyridine/divinylbenzene co-polymerization at different ratios and dichloromethane as porogen. Imprinting was done with a template mixture of phenanthrene and pyrene yielding a broad-specific polymer for PAHs with a maximum binding capacity (Q) of ~32 μg B[a]P per 50 mg of polymer. The vegetable oil/n-hexane mixture (1:1, (v/v)) was pre-extracted with acetonitrile, the solvent evaporated, the residue reconstituted in n-hexane and subjected to MISPE. The successive washing with n-hexane and isopropanol revealed most suitable to remove lipid matrix constituents. After elution of bound PAHs from MISPE column with dichloromethane, the solvent was evaporated, the residue reconstituted with dimethyl sulfoxide and diluted 100-fold with methanol/water (10:90, (v/v)) for analysis of B[a]P equivalents with an ELISA. The B[a]P recovery rates in spiked vegetable oil samples of different fatty acid composition were determined between 63% and 114%. The presence of multiple PAHs in the oil sample, because of MIP selectivity and cross-reactivity of the ELISA, could yield overestimated B[a]P values. PMID:24887045

  2. Analysis of Benzo[a]pyrene in Vegetable Oils Using Molecularly Imprinted Solid Phase Extraction (MISPE Coupled with Enzyme-Linked Immunosorbent Assay (ELISA

    Directory of Open Access Journals (Sweden)

    Michael Pschenitza

    2014-05-01

    Full Text Available This paper describes the development of a molecularly imprinted polymer-based solid phase extraction (MISPE method coupled with enzyme-linked immunosorbent assay (ELISA for determination of the PAH benzo[a]pyrene (B[a]P in vegetable oils. Different molecularly imprinted polymers (MIPs were prepared using non-covalent 4-vinylpyridine/divinylbenzene co-polymerization at different ratios and dichloromethane as porogen. Imprinting was done with a template mixture of phenanthrene and pyrene yielding a broad-specific polymer for PAHs with a maximum binding capacity (Q of ~32 μg B[a]P per 50 mg of polymer. The vegetable oil/n-hexane mixture (1:1, (v/v was pre-extracted with acetonitrile, the solvent evaporated, the residue reconstituted in n-hexane and subjected to MISPE. The successive washing with n-hexane and isopropanol revealed most suitable to remove lipid matrix constituents. After elution of bound PAHs from MISPE column with dichloromethane, the solvent was evaporated, the residue reconstituted with dimethyl sulfoxide and diluted 100-fold with methanol/water (10:90, (v/v for analysis of B[a]P equivalents with an ELISA. The B[a]P recovery rates in spiked vegetable oil samples of different fatty acid composition were determined between 63% and 114%. The presence of multiple PAHs in the oil sample, because of MIP selectivity and cross-reactivity of the ELISA, could yield overestimated B[a]P values.

  3. Particle-Associated Ambient Benzo[a]pyrene and Levels of Urinary 1-Hydroxypyrene in a Non-occupationally Exposed Population of Adults and Children in Lanzhou, China.

    Science.gov (United States)

    Yu, Yunjiang; Wang, Qiong; Li, Liangzhong; Liu, Zien; Sun, Peng; Zhang, Yanping; Lin, Haipeng; Xiang, Mingdeng; Li, Hui; Lin, Bigui

    2016-03-01

    Concentrations of benzo[a]pyrene (B[a]P) in ambient air from different areas in Lanzhou city in northwest of China, and its metabolite 1-hydroxypyrene (1-OHP) in the urine of resident children and adults were determined by using gas chromatography/mass spectrometry and high performance liquid chromatography. Results showed that the atmospheric environmental concentration of B[a]P varied significantly from one part of the city to another with levels of 150 ng/m(3) in the industrial area of Xigu and 73.8 ng/m(3) in the agricultural area of Yuzhong. The geometric mean urinary 1-OHP concentration was 0.42 µmol/mol-creatinine, with a range of means between 0.067 and 2.05 for the various population sub-groups. The non-occupationally exposed populations' age, gender and area of residence were the major factors that influenced urinary 1-OHP levels. The health risks of B[a]P for adults and children in Xigu and for children in Yuzhong exceeded the acceptable level (1 × 10(-4)) of the US Environmental Protection Agency. PMID:26841792

  4. Assessment of Industry-Induced Urban Human Health Risks Related to Benzo[a]pyrene based on a Multimedia Fugacity Model: Case Study of Nanjing, China

    Directory of Open Access Journals (Sweden)

    Linyu Xu

    2015-05-01

    Full Text Available Large amounts of organic pollutants emitted from industries have accumulated and caused serious human health risks, especially in urban areas with rapid industrialization. This paper focused on the carcinogen benzo[a]pyrene (BaP from industrial effluent and gaseous emissions, and established a multi-pathway exposure model based on a Level IV multimedia fugacity model to analyze the human health risks in a city that has undergone rapid industrialization. In this study, GIS tools combined with land-use data was introduced to analyze smaller spatial scales so as to enhance the spatial resolution of the results. An uncertainty analysis using a Monte Carlo simulation was also conducted to illustrate the rationale of the probabilistic assessment mode rather than deterministic assessment. Finally, the results of the case study in Nanjing, China indicated the annual average human cancer risk induced by local industrial emissions during 2002–2008 (lowest at 1.99´10–6 in 2008 and highest at 3.34´10–6 in 2004, which was lower than the USEPA prescriptive level (1´10–6–1´10–4 but cannot be neglected in the long term. The study results could not only instruct the BaP health risk management but also help future health risk prediction and control.

  5. Molecular cloning and differential expression patterns of sigma and omega glutathione S-transferases from Venerupis philippinarum to heavy metals and benzo[a]pyrene exposure

    Science.gov (United States)

    Zhang, Linbao; Wu, Huifeng; Liu, Xiaoli; Chen, Leilei; Wang, Qing; Zhao, Jianmin; You, Liping

    2012-05-01

    Glutathione S-transferases (GSTs) are a class of enzymes that facilitate the detoxification of xenobiotics, and also play important roles in antioxidant defense. We identified two glutathione S-transferase isoforms (VpGSTS, sigma GST; VpGSTO, omega GST) from Venerupis philippinarum by RACE approaches. The open reading frames of VpGSTS and VpGSTO were of 612 bp and 729 bp, encoding 203 and 242 amino acids with an estimated molecular mass of 22.88 and 27.94 kDa, respectively. The expression profiles of VpGSTS and VpGSTO responded to heavy metals and benzo[a]pyrene (B[a]P) exposure were investigated by quantitative real-time RT-PCR. The expression of VpGSTS and VpGSTO were both rapidly up-regulated, however, they showed differential expression patterns to different toxicants. Cd displayed stronger induction of VpGSTS expression with an approximately 12-fold increase than that of VpGSTO with a maximum 6.4-fold rise. Cu exposure resulted in similar expression patterns for both VpGSTS and VpGSTO. For B[a]P exposure, the maximum induction of VpGSTO was approximately two times higher than that of VpGSTS. Altogether, these findings implied the involvement of VpGSTS and VpGSTO in host antioxidant responses, and highlighted their potential as a biomarker to Cd and B[a]P exposure.

  6. Mechanism-based inactivation of cytochrome P-450 dependent benzo[a]pyrene hydroxylase activity by acetylenic and olefinic polycyclic arylhydrocarbons

    International Nuclear Information System (INIS)

    A series of aryl acetylenes and aryl olefins have been examined as substrates and inhibitors of cytochrome P-450 dependent monooxygenases in liver microsomes from 5,6-benzoflavone or phenobarbital pretreated rats. 1-Ethynylpyrene (EP), 3-ethynylperylene (EPL), cis- and trans-1-(2-bromo-vinyl)pyrene (c-BVP and t-BVP), and 1-allylpyrene (AP) serve as mechanism-based irreversible inactivators (suicide inhibitors) of benzo(a)pyrene (BP) hydroxylase, while 1-vinyl-pyrene (VP) and phenyl 1-pyrenyl acetylene (PPA) do not cause a detectable suicide inhibition of the BP hydroxylase. The mechanism-based loss of BP hydroxylase activity caused by the aryl acetylenes is not accompanied by a corresponding loss of the P-450 content of the microsomes. In the presence of NADPH, 3H-labeled EP covalently attached to P-450 isozymes with a measured stoichiometry of one mole of EP per mole of the P-450 heme. The results of the effects of these aryl derivatives in the mammalian cell-mediated mutagenesis assay and toxicity assay show that none of the compounds examined nor any of the their metabolites produced in the incubation system are cytotoxic to V79 cells

  7. Preliminary evidence of the role of hydrogen peroxide in the degradation of benzo[a]pyrene by a non-white rot fungus Fusarium solani

    International Nuclear Information System (INIS)

    In order to study the enzymatic mechanisms involved in the successive steps of BaP degradation by a Deuteromycete fungus Fusarium solani, we developed an indirect approach by using inhibitors of enzymes. We used either specific inhibitors of peroxidases (i.e. salicylhydroxamic acid) and of cytochrome P-450 (i.e. piperonyl butoxyde) or inhibitors of both enzymes (i.e. potassium cyanide). Surprisingly, no expected decrease of BaP degradation was observed with most inhibitors tested. On the contrary, more BaP was degraded. Only butylated hydroxytoluene, which acts as a free radical scavenger, inhibited BaP degradation. The inhibition of these enzymes, which use H2O2 as a cosubstrat, might have resulted in an increase of hydrogen peroxide availability in the fungal cultures. This enhancement could induce formation of reactive oxygen species (ROS) which might be the agents that initiate benzo[a]pyrene oxidation. This study proposed a hypothetic alternative metabolic pathway involved in PAH metabolism by Fusarium solani. - An alternative metabolic pathway was demonstrated

  8. Alterations in benzo(A)pyrene metabolism and in vivo binding to hepatic DNA in rats red diets containing menhaden oil

    Energy Technology Data Exchange (ETDEWEB)

    Wade, A.E.; Dharwadkar, S.

    1987-01-01

    Polyunsaturated fatty acids of the omega-6 type have been shown to support the mixed function oxidases (MFO) responsible for carcinogen activation and to promote tumorigenesis in laboratory animals. The omega-3 fatty acids contained in menhaden oil (MO) have been shown to enhance MFO activity and increase the binding of Benzo(a)pyrene (B(a)P) metabolites to calf thymus DNA in an in vitro microsomal system. Rats fed two levels of MO (0.5% and 20%) for 11 days received a single i.p. dose of (/sup 3/H)B(a)P (5 m Ci/kg) dissolved in DMSO. At selected time intervals thereafter rats were killed, blood withdrawn, livers removed and DNA extracted. Hepatic microsomes were recovered from control rats on each diet at the time of B(a)P administration to assess MFO activities. Binding of B(a)P to DNA was higher in rats fed the 20% MO diet suggesting an increased rate of B(a)P activation. Blood levels of B(a)P were elevated at 16 and 24 hours post B(a)P, however no differences in urine concentrations were observed. Elevations in concentration of cytochrome P-450, ethoxycoumarin dealkylase, and glutathione S-transferase suggest that omega-3 fatty acids of menhaden fish oil support MFO related reactions not unlike the omega-6 fatty acids.

  9. A role for the androgen metabolite, 5alpha-androstane-3beta,17beta-diol, in modulating oestrogen receptor beta-mediated regulation of hormonal stress reactivity.

    Science.gov (United States)

    Handa, R J; Weiser, M J; Zuloaga, D G

    2009-03-01

    Activation of the hypothalamic-pituitary-adrenal (HPA) axis is a basic response of animals to environmental perturbations that threaten homeostasis. These responses are regulated by neurones in the paraventricular nucleus of the hypothalamus (PVN) that synthesise and secrete corticotrophin-releasing hormone (CRH). Other PVN neuropeptides, such as arginine vasopressin and oxytocin, can also modulate activity of CRH neurones in the PVN and enhance CRH secretagogue activity of the anterior pituitary gland. In rodents, sex differences in HPA reactivity are well established; females exhibit a more robust activation of the HPA axis after stress than do males. These sex differences primarily result from opposing actions of sex steroids, testosterone and oestrogen, on HPA function. Ostreogen enhances stress activated adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) secretion, whereas testosterone decreases the gain of the HPA axis and inhibits ACTH and CORT responses to stress. Data show that androgens can act directly on PVN neurones in the male rat through a novel pathway involving oestrogen receptor (ER)beta, whereas oestrogen acts predominantly through ERalpha. Thus, we examined the hypothesis that, in males, testosterone suppresses HPA function via an androgen metabolite that binds ERbeta. Clues to the neurobiological mechanisms underlying such a novel action can be gleaned from studies showing extensive colocalisation of ERbeta in oxytocin-containing cells of the PVN. Hence, in this review, we address the possibility that testosterone inhibits HPA reactivity by metabolising to 5alpha-androstane-3beta,17beta-diol, a compound that binds ERbeta and regulates oxytocin containing neurones of the PVN. These findings suggest a re-evaluation of studies examining pathways for androgen receptor signalling. PMID:19207807

  10. A Role for the Androgen Metabolite, 5α-Androstane-3β,17β-Diol, in Modulating Oestrogen Receptor β-Mediated Regulation of Hormonal Stress Reactivity

    Science.gov (United States)

    Handa, R. J.; Weiser, M. J.; Zuloaga, D. G.

    2009-01-01

    Activation of the hypothalamic-pituitary-adrenal (HPA) axis is a basic response of animals to environmental perturbations that threaten homeostasis. These responses are regulated by neurones in the paraventricular nucleus of the hypothalamus (PVN) that synthesise and secrete corticotrophin-releasing hormone (CRH). Other PVN neuropeptides, such as arginine vasopressin and oxytocin, can also modulate activity of CRH neurones in the PVN and enhance CRH secretagogue activity of the anterior pituitary gland. In rodents, sex differences in HPA reactivity are well established; females exhibit a more robust activation of the HPA axis after stress than do males. These sex differences primarily result from opposing actions of sex steroids, testosterone and oestrogen, on HPA function. Ostreogen enhances stress activated adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) secretion, whereas testosterone decreases the gain of the HPA axis and inhibits ACTH and CORT responses to stress. Data show that androgens can act directly on PVN neurones in the male rat through a novel pathway involving oestrogen receptor (ER)β, whereas oestrogen acts predominantly through ERα. Thus, we examined the hypothesis that, in males, testosterone suppresses HPA function via an androgen metabolite that binds ERβ. Clues to the neurobiological mechanisms underlying such a novel action can be gleaned from studies showing extensive colocalisation of ERβ in oxytocin-containing cells of the PVN. Hence, in this review, we address the possibility that testosterone inhibits HPA reactivity by metabolising to 5α-androstane-3β,17β-diol, a compound that binds ERβ and regulates oxytocin containing neurones of the PVN. These findings suggest a re-evaluation of studies examining pathways for androgen receptor signalling. PMID:19207807

  11. (Eco)toxicological effects of 2,4,7,9-tetramethyl-5-decyne-4,7-diol (TMDD) in zebrafish (Danio rerio) and permanent fish cell cultures.

    Science.gov (United States)

    Vincze, Krisztina; Gehring, Martin; Braunbeck, Thomas

    2014-01-01

    2,4,7,9-tetramethyl-5-decyne-4,7-diol (TMDD) is a high-production volume chemical used in paper, ink, pesticide, and adhesive industries as a wetting and anti-foaming agent. The physicochemical properties and slow biodegradation rate of TMDD indicate a low bioaccumulation potential but a high prevalence in the environment. As a consequence, TMDD has been detected in several European rivers in the nanogram per liter and lower microgram per liter range; however, its environmental risk to aquatic organisms is considered low. Recent studies almost exclusively focused on acute effects by TMDD, little is known about cytotoxic and genotoxic effects, reproduction and developmental toxicity, endocrine disruption, and any kind of long-term toxicity and carcinogenicity so far. The present study aims to provide more specific baseline information on the ecotoxicological effects of TMDD in fish. For this end, cyto- and genotoxicity assays were carried out in vitro with the permanent fish cell line RTL-W1; in addition, in vivo studies were conducted with the early life stages of zebrafish (Danio rerio) in order to fill the data gaps in developmental toxicity and endocrine disruption. TMDD showed a cytotoxic and slight genotoxic potential in fish cell lines; moreover, various sublethal and lethal effects could be detected in developing zebrafish embryos. There was no evidence of endocrine-disrupting effects by TMDD; however, mortality following prolonged exposure to TMDD during fish sexual development test was clearly higher than mortality in the fish embryo test after 96-h exposure. Our results thus confirmed previous findings of laboratory screening tests, suggesting short-term toxic effects of TMDD in the intermediate, and long-term effects in the lower milligram per liter range. PMID:24687796

  12. 4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol}, 1 a novel resveratrol analog, differentially regulates estrogen receptors α and β in breast cancer cells.

    Science.gov (United States)

    Ronghe, Amruta; Chatterjee, Anwesha; Singh, Bhupendra; Dandawate, Prasad; Abdalla, Fatma; Bhat, Nimee K; Padhye, Subhash; Bhat, Hari K

    2016-06-15

    Breast cancer is a public health concern worldwide. Prolonged exposure to estrogens has been implicated in the development of breast neoplasms. Epidemiologic and experimental evidence suggest a chemopreventive role of phytoestrogens in breast cancers. Resveratrol, a naturally occurring phytoestrogen, has been shown to have potent anti-cancer properties. However, poor efficacy and bioavailability have prevented the use of resveratrol in clinics. In order to address these problems, we have synthesized a combinatorial library of azaresveratrol analogs and tested them for their ability to inhibit the proliferation of breast cancer cells. We have recently shown that 4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol} (TIMBD), has better anti-cancer properties than resveratrol and any other resveratrol analog we have synthesized so far. The objective of this study was to investigate the regulation of estrogen receptors (ERs) α and β by TIMBD in breast cancer cell lines. We demonstrate that TIMBD significantly induces the mRNA and protein expression levels of ERβ and inhibits that of ERα. TIMBD inhibits mRNA and protein expression levels of oncogene c-Myc, and cell cycle protein cyclin D1, which are important regulators of cellular proliferation. TIMBD significantly induces protein expression levels of tumor suppressor genes p53 and p21 in MCF-7 cells. TIMBD inhibits c-Myc in an ERβ-dependent fashion in MCF-10A and ERβ1-transfected MDA-MB-231 cells, suggesting regulation of ERs as an important upstream mechanism of this analog. ERβ plays a partial role in inhibition of proliferation by TIMBD while ERα overexpression does not significantly affect TIMBD's inhibition. PMID:26970359

  13. Protection of rats against 3-butene-1,2-diol-induced hepatotoxicity and hypoglycemia by N-acetyl-L-cysteine

    International Nuclear Information System (INIS)

    3-Butene-1,2-diol (BDD), an allylic alcohol and major metabolite of 1,3-butadiene, has previously been shown to cause hepatotoxicity and hypoglycemia in male Sprague-Dawley rats, but the mechanisms of toxicity were unclear. In this study, rats were administered BDD (250 mg/kg) or saline, ip, and serum insulin levels, hepatic lactate levels, and hepatic cellular and mitochondrial GSH, GSSG, ATP, and ADP levels were measured 1 or 4 h after treatment. The results show that serum insulin levels were not causing the hypoglycemia and that the hypoglycemia was not caused by an enhancement of the metabolism of pyruvate to lactate because hepatic lactate levels were either similar (1 h) or lower (4 h) than controls. However, both hepatic cellular and mitochondrial GSH and GSSG levels were severely depleted 1 and 4 h after treatment and the mitochondrial ATP/ADP ratio was also lowered 4 h after treatment relative to controls. Because these results suggested a role for hepatic cellular and mitochondrial GSH in BDD toxicity, additional rats were administered N-acetyl-L-cysteine (NAC; 200 mg/kg) 15 min after BDD administration. NAC treatment partially prevented depletion of hepatic cellular and mitochondrial GSH and preserved the mitochondrial ATP/ADP ratio. NAC also prevented the severe depletion of serum glucose concentration and the elevation of serum alanine aminotransferase activity after BDD treatment without affecting the plasma concentration of BDD. Thus, depletion of hepatic cellular and mitochondrial GSH followed by the decrease in the mitochondrial ATP/ADP ratio was likely contributing to the mechanisms of hepatotoxicity and hypoglycemia in the rat

  14. Endocrine disruptive actions of inhaled benzo(a)pyrene on ovarian function and fetal survival in fisher F-344 adult rats.

    Science.gov (United States)

    Archibong, Anthony E; Ramesh, Aramandla; Inyang, Frank; Niaz, Mohammad S; Hood, Darryl B; Kopsombut, Prapaporn

    2012-12-01

    This study evaluated the effect of inhaled BaP on female reproductive function. Rats were exposed to 50, or 75 or 100 μg BaP/m(3), 4 h a day for 14 days via inhalation. Plasma E(2), P(4), LH and FSH concentrations were determined. Ovarian BaP metabolism and aryl hydrocarbon hydrolase (AHH) activity at proestrus were determined and fertility evaluations were conducted. Ovulation rate and number of pups/litter were reduced in rats exposed to 100 μg BaP/m(3) compared with other treatment and control groups. Plasma concentrations of E(2), and LH were significantly reduced at proestrus in BaP-exposed versus those of controls whereas those of P(4) were significantly reduced at diestrus I. The activity of AHH in ovarian and liver tissues and concentrations of BaP 7,8-diol and BaP 3,6-dione metabolites increased in an exposure concentration-dependent manner. These data suggest that exposure of rats to BaP prior to mating contributes to reduced ovarian function and fetal survival. PMID:23059060

  15. Epoxidation and Reduction of DHEA, 1,4,6-Androstatrien-3-one and 4,6-Androstadien-3β,17β-diol

    Directory of Open Access Journals (Sweden)

    Eunjeong Kim

    2005-05-01

    Full Text Available Dehydroepiandrosterone (DHEA reacted with m-chloroperoxybenzoic acid(m-CPBA to form 3β-hydroxy-5α,6α-epoxyandrostan-17-one (1, but it did not reactwith 30% H2O2. 1,4,6-Androstatrien-3,17-dione (2 was obtained from DHEA and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in dioxane. Compound 2 was reacted with 30%H2O2 and 5% NaOH in methanol to give 1α,2α-epoxy-4,6-androstadien-3,17-dione (3,which was stereoselectively reduced with NaBH4 to form 1α,2α-epoxy-4,6-androstadien-3β,17β-diol (7 and reacted with Li metal in absolute ethanol-tetrahydrofuran mixture togive 2-ethoxy-1,4,6-androstatrien-3,17-dione (8. Compound 2 was also epoxidized withm-CPBA in dichloromethane to afford 6α,7α-epoxy-1,4-androstadien-3,17-dione (4,which was reacted with NaBH4 to synthesize 6α,7α-epoxy-4-androsten-3β,17β-diol (9.Compound 4 was reduced with Li metal in absolute ethanol-tetrahydrofuran mixture toform 7β-ethoxy-6α-hydroxy-1,4-androstadien-3,17-dione (10. Compound 2 was reducedwith NaBH4 in absolute ethanol to form 4,6-androstadien-3β,17β-diol (5, which wasreacted with 30% H2O2 to give the original compound, but which reacted with m-CPBAto give 4β,5β-epoxy-6-androsten-3β,17β-diol (6.

  16. Thesis Abstract Study of biochemical changes in blood and various organs of Phrynops geoffroanus (Schweigger, 1812) (Testudines: Chelidae) collected in contaminated environment or exposed to benzo[a]pyrene.

    Science.gov (United States)

    Silva, M I A; Silva, T L; Almeida, E A

    2016-01-01

    The aquatic organisms are often exposed to a wide variety of chemicals, whose individual components are likely to produce different responses within the organisms and/or interact producing additive, synergistic or antagonistic toxic effects. Most of these substances are potentially cytotoxic, genotoxic or carcinogenic, such as polycyclic aromatic hydrocarbons (PAHs). The Phrynops geoffroanus species ("Geoffroy's side-necked turtle", Schweigger, 1812) is widely distributed in tropical and temperate areas of South America. This species is commonly found in impacted areas, and polluted rivers that cross the urban area and receive domestic and industrial wastewater effluents. In these environments, freshwater turtles are exposed to ecological pressures that threaten their conservation and can influence the animal life habits and physiological conditions. The objective of this study was to evaluate the biochemical changes in various organs (liver, heart, lung, pancreas, brain, small and large intestines) of P. geoffroanus from contaminated environment by human activities (sewage and industrial wastewater effluents) (Step 1) or exposed to benzo[a]pyrene, a PAHs model compound, for 7 days (Step 2). For this, we analyzed the responses of systems related to phases I and II of xenobiotics biotransformation, main antioxidant enzyme activities and malondialdehyde (MDA) levels, indicative of oxidative stress, as biomarkers for biomonitoring of pollutants impact. Furthermore, we have assessed the gamma glutamyl transferase enzymatic activity and DNA fragmentation by comet assay, in P. geoffroanus blood exposed to benzo[a]pyrene, in order to identify hepatic changes and genotoxicity according to the tested doses of this compound. The first step of this study analysis revealed an important influence of contamination by domestic and industrial wastewater effluents in free-living freshwater turtles that presented a series of changes in biomarkers analyzed. We observed higher MDA

  17. 14C glucose uptake and turnover, a biomarker in benzo(a)pyrene induced lung carcinogenesis: role of curcumin and resveratrol

    International Nuclear Information System (INIS)

    Full text: The aim of the present study was to explore the synergistic potential of curcumin and resveratrol in modulation of glucose metabolism by studying 14C glucose uptake, turnover in the lung slices and ultra-histoarchitectural changes during benzo(a)pyrene (BP) induced lung carcinogenesis in mice. The mice were segregated into five treatment groups which included group I (normal control), group II (BP treated), group III (BP+curcumin treated), group IV (BP+resveratrol treated) and group V (BP+curcumin+resveratrol treated). Animals in Group II were given a single intraperitoneal injection of Benzo(a)pyrene in corn oil at a dose level of 100mg/Kg body weight. Group III animals were given curcumin orally in drinking water at a dose level of 60 mg /Kg/ body weight, thrice a week. Animals in Group IV were given resveratrol orally at a dose level of 5.7 microgram/ml drinking water, thrice a week. Animals in group V were given a combined treatment of curcumin and resveratrol in a similar manner as was given to group III and group IV animals, respectively. All the animals had free access to the diet and water and the treatments continued for a total duration of 22 weeks. The morphological and ultra-histoachitectural analyses confirmed lung carcinogenesis, in the BP treated mice. Tumor incidence and tumor multiplicity were observed to be 88% and 1.75 respectively in the BP treated mice. A statistically significant increase in the uptake of 14C glucose was observed in the lung slices of BP treated mice. Further, radiorespirometric analyses of 14C turnover also showed a significant increase in the lung slices of BP treated mice. The ultra-histoarchitecture of the BP treated mice revealed disruption in cellular integrity along with nuclear deformation. Mitochondria were swollen and cytoplasm appeared granular along with extensive vacuolization. Further, spaces between the endothelium, epithelium and basement membrane indicative of lung injury and edema were observed in

  18. Xeroderma pigmentosum, complementation group D expression in H1299 lung cancer cells following benzo[a]pyrene exposure as well as in head and neck cancer patients.

    Science.gov (United States)

    Lin, Chang-Shen; Chiou, Wen-Yen; Lee, Ka-Wo; Chen, Tzu-Fen; Lin, Yuan-Jen; Huang, Jau-Ling

    2016-01-01

    DNA repair genes play critical roles in response to carcinogen-induced and anticancer therapy-induced DNA damage. Benzo[a]pyrene (BaP), the most carcinogenic polycyclic aromatic hydrocarbon (PAH), is classified as a group 1 carcinogen by International Agency for Research on Cancer. The aims of this study were to (1) evaluate the effects of BaP on DNA repair activity and expression of DNA repair genes in vitro and (2) examine the role of xeroderma pigmentosum, complementation group D (XPD) mRNA expression in human head and neck cancers. Host cell reactivation assay showed that BaP inhibited nucleotide excision repair in H1299 lung cancer cells. DNA repair through the non-homologous end-joining pathway was not affected by BaP. Real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) and Western blot demonstrated that XPD was downregulated by BaP treatment. BaP exposure did not apparently affect expression of another 11 DNA repair genes. BaP treatment increased the DNA damage marker γ-H2AX and ultraviolet (UV) sensitivity, supporting an impairment of DNA repair in BaP-treated cells. XPD expression was also examined by quantitative RT-PCR in 68 head and neck cancers, and a lower XPD mRNA level was found in smokers' cancer specimens. Importantly, reduced XPD expression was correlated with patient 5-year overall survival rate (35 vs. 56%) and was an independent prognostic factor (hazard ratio: 2.27). Data demonstrated that XPD downregulation was correlated with BaP exposure and human head and neck cancer survival. PMID:26731659

  19. Neonatal Benzo[a]pyrene Exposure Induces Oxidative Stress and DNA Damage Causing Neurobehavioural Changes during the Early Adolescence Period in Rats.

    Science.gov (United States)

    Patel, Bhupesh; Das, Saroj Kumar; Patri, Manorama

    2016-01-01

    Humans are exposed to polycyclic aromatic hydrocarbons (PAHs) by ingestion of contaminated food and water. Prenatal exposure to benzo[a]pyrene (B[a]P) like PAHs through the placental barrier and neonatal exposure by breast milk and the environment may affect early brain development. In the present study, single intracisternal administration of B[a]P (0.2 and 2.0 µg/kg body weight) to male Wistar rat pups at postnatal day 5 (PND5) was carried out to study its specific effect on neonatal brain development and its consequences at PND30. B[a]P administration showed a significant increase in exploratory and anxiolytic-like behaviour with elevated hippocampal lipid peroxidation and protein oxidation at PND30. Further, DNA damage was estimated in vitro (Neuro2a and C6 cell lines) by the comet assay, and oxidative DNA damage of hippocampal sections was measured in vivo following exposure to B[a]P. DNA strand breaks (single and double) significantly increased due to B[a]P at PND30 in hippocampal neurons and increased the nuclear tail moment in Neuro2a cells. Hippocampal 8-oxo-2'-deoxyguanosine production was significantly elevated showing expression of more TUNEL-positive cells in both doses of B[a]P. Histological studies also revealed a significant reduction in mean area and perimeter of hippocampal neurons in rats treated with B[a]P 2.0 μg/kg, when compared to naïve and control rats. B[a]P significantly increased anxiolytic-like behaviour and oxidative DNA damage in the hippocampus causing apoptosis that may lead to neurodegeneration in adolescence. The findings of the present study address the potential role of B[a]P in inducing oxidative stress-mediated neurodegeneration in the hippocampus through oxidative DNA damage in the early adolescence period of rats. PMID:27271523

  20. Modulation of Benzo[a]pyrene induced immunotoxicity in mice actively immunized with a B[a]P-diphtheria toxoid conjugate

    International Nuclear Information System (INIS)

    Benzo[a]pyrene (B[a]P) is a small molecular weight carcinogen and the prototype of polycyclic aromatic hydrocarbons (PAHs). While these compounds are primarily known for their carcinogenicity, B[a]P and its metabolites are also toxic for mammalian immune cells. To develop a prophylactic immune strategy against detrimental effects of B[a]P, we have immunized mice with a B[a]P-diphtheria toxoid conjugate vaccine. We showed that high levels of antibodies against B[a]P and its metabolites modulate the redistribution of these PAHs in the blood. After immunization, increased levels of B[a]P and its metabolites were recovered in the blood. B[a]P significantly suppressed the proliferative response of both T and B cells after a sub-acute administration, an effect that was completely reversed by vaccination. In immunized mice also the immunotoxic effect of B[a]P on IFN-γ, IL-12, TNF-α production and the reduced B cell activation was restored. Finally, our results showed that specific antibodies inhibited the induction of Cyp1a1 by B[a]P in lymphocytes and Cyp1b1 in the liver, enzymes that are known to convert the procarcinogen B[a]P to the ultimate DNA-adduct forming metabolite, a major risk factor of chemical carcinogenesis. Thus, we demonstrate that vaccination with a B[a]P conjugate vaccine based on a carrier protein used in licensed human vaccines reduces immunotoxicity and possibly other detrimental effects associated with B[a]P.

  1. In vitro Study on Role of Hsp70 Expression in DNA Damage of Human Embryonic Lung Cells Exposed to Benzo[a]pyrene

    Institute of Scientific and Technical Information of China (English)

    YA-JUAN GAO; CHENG-FENG XIAO; SHENG CHEN; RUI-BO WANG; HAN-ZHEN HE; ROBERT M TANGUAY; TANG-CHUN WU

    2004-01-01

    Objective Benzo[a]pyrene (B[a]P), a ubiquitous environmental pollutant, is a potent procarcinogen and mutagen that can elicit tumors, leading to malignancy. Heat shock proteins (Hsp) have been shown to protect cells against damages caused by various stresses including exposure to numerous chemicals. Whether Hsps, or more specifically Hsp70, are involved in repair of B[a]P-induced DNA damage is currently unknown. Methods We assessed the potential role of the inducible form of Hsp70 in B[a]P-induced DNA damage of human embryonic lung (HEL) cells using immunoblot and the comet assay (i.e., the single cell gel electrophoresis assay). Results Exposure to B[a]P induced a dose-dependent decrease in the level of Hsp70, but a dose-dependent increase in DNA damage both in untreated (control) HEL cells and in cells preconditioned by a heat treatment. Heat preconditioning prior to B[a]P exposure potentiated the effect of B[a]P at a low dose (10 (mol/L), but appeared to be protective at higher doses. There was a negative correlation between Hsp70 level and DNA damage in the non-preheated as well as in the preconditioned cells. Conclusion These data suggest that exposure of HEL cells to B[a]P may induce a dose-dependent reduction in the levels of the inducible Hsp70. The detailed mechanisms for the reduction of Hsp70 levels by B[a]P and the role of Hsp70 in DNA damage under different concentrations of B[a]P remains to be determined.

  2. Benzo(a)pyrenediolepoxide-hemoglobin adducts and 3-hydroxy-benzo(a)pyrene urinary excretion profiles in rats subchronically exposed to benzo(a)pyrene.

    Science.gov (United States)

    Bouchard, M; Viau, C

    1995-01-01

    The time profiles of benzo(a)pyrenediolepoxide (BaPDE)-hemoglobin (Hb) adduct formation and 3-hydroxybenzo(a)pyrene (3-OHBaP) urinary excretion were studied in male Sprague-Dawley rats exposed to daily benzo(a)pyrene (BaP) intraperitoneal doses of 1.25, 6.25, and 31.25 mumol/kg administered Tuesday to Friday for 4 consecutive weeks. Blood was withdrawn weekly, on Tuesdays, prior to dosing. Twenty-four-hour urine samples were collected on Mondays (following 72 h without treatment) and Thursdays. Analytes were quantified by high performance liquid chromatography (HPLC)/fluorescence. Exposure to BaP resulted in the accumulation of BaPDE-Hb adducts, reaching an average of 1.2 +/- 0.3, 8.3 +/- 1.9, and 38.2 +/- 6.1 pmol/g Hb for the 1.25, 6.25, and 31.25 mumol/kg per day doses after 4 weeks of treatment. The expected saw tooth excretion profile of 3-OHBaP was observed, with peaks on Thursdays and troughs on Mondays, and showed a progressive rise on both Mondays and Thursdays. Increase in Monday values with time suggested a possible increase in BaP body burden during exposure. To verify this aspect further, the urinary excretion kinetic of 3-OHBaP following acute intraperitoneal dosing (31.25 mumol/kg) was determined. Urine samples were collected at frequent timed intervals for up to 164 h post-dosing. Two-step elimination was observed, the second step having a half-life of 25 h, presumably linked to the slow release of BaP accumulated in fatty tissues upon repeated treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8534197

  3. Disturbance of Bcl-2, Bax, Caspase-3, Ki-67 and C-myc expression in acute and subchronic exposure to benzo(a)pyrene in cervix.

    Science.gov (United States)

    Gao, Meili; Li, Yongfei; Ji, Xiaoying; Xue, Xiaochang; Chen, Lan; Feng, Guodong; Zhang, Huqin; Wang, Huichun; Shah, Walayat; Hou, Zhanwu; Kong, Yu

    2016-03-01

    Epidemiological studies have demonstrated that cigarette smoking is an important cofactor or an independent risk factor for the development of cervical cancer. Benzo(a)pyrene (BaP) is one of the most potent tobacco smoke carcinogens in tobacco smoke. BaP induced DNA damage and over expression in p53 cervical tissue of mice as demonstrated in our previous study. Here we present the findings of exposure to BaP on the expression of Bcl-2, C-myc, Ki-67, Caspase-3 and Bax genes in mouse cervix. Acute intraperitoneal administration of BaP (12.5, 25, 50, 100mg/kg body weight) to ICR female mice induced a significant increase in Bcl-2, C-myc, Ki-67 mRNA and protein level till 72h except in Bcl-2 at 24h with 12.5, 25, 50mg/kg as well as at 48h with 12.5mg/kg body weight post treatment. A significant increase was also seen in Caspase-3 and Bax mRNA and protein level with peak level at 24h and gradual decrease till 72h, however, the expression of caspase-3 increased while that of Bax decreased with increasing dose of Bap after 24h. In sub chronic intraperitoneal and oral gavage administration of BaP (2.5, 5, 10mg/kg body weight), similar significant increase was observed for all the examined genes as compared to the control and vehicle groups, however the expression of Bax decreased in a dose dependent manner. The findings of this study will help in further understanding the molecular mechanism of BaP induced carcinogenesis of cervical cancer. PMID:26709117

  4. Sensitivity analysis of biodiesel blends on Benzo[a]pyrene and main emissions using MOVES: A case study in Temuco, Chile.

    Science.gov (United States)

    Pino-Cortés, Ernesto; Díaz-Robles, Luis A; Cubillos, Francisco; Fu, Joshua S; Vergara-Fernández, Alberto

    2015-12-15

    Temuco is one of the most highly wood-smoke polluted cities in Chile; however, the diesel mobile sources are growing very fast in the past 10 years and so far very few studies have been done. The main goal of this research was to develop a 2013 emission inventory of criteria pollutants and Benzo[a]pyrene (BaP) and to evaluate the use of six biodiesel blends of 0%, 1%, 4%, 8%, 12%, and 20% by volume of fuel in diesel motors from the vehicle fleet within the mentioned areas using the Motor Vehicle Emission Simulator (MOVES). Input parameters for the base year 2005 were estimated to implement and adapt the model in Chile, while results of NOx, PM10, PM2.5, NH3, CO2 equivalent and SO2 were compared with the Chilean Emission Inventory estimated by the model "Methodology for the Calculation of Vehicle Emissions." The 2013 emissions reduced with respect to 2005, in the majority of the contaminants analyzed, despite the 47% increase in the annual miles traveled. Using biodiesel blends, an emission reduction was estimated at up to 15% in particulate matter, BaP, and CO for the year 2013, as well as an increment of 2% in NOx emissions, attributed to low sulfur content (50 ppm) in the diesel and the antiquity of the vehicle fleet. The results obtained gave evidence of the influence of the biodiesel use in the pollutant emissions to improve the Chilean air quality, as well as providing a strategy for this air quality management. PMID:26282769

  5. Subchronic oral administration of Benzo[a]pyrene impairs motor and cognitive behavior and modulates S100B levels and MAPKs in rats.

    Science.gov (United States)

    Maciel, Erica Santos; Biasibetti, Regina; Costa, Ana Paula; Lunardi, Paula; Schunck, Rebeca Vargas Antunes; Becker, Gabriela Curbeti; Arbo, Marcelo Dutra; Dallegrave, Eliane; Gonçalves, Carlos Alberto; Saldiva, Paulo H Nascimento; Garcia, Solange Cristina; Leal, Rodrigo Bainy; Leal, Mirna Bainy

    2014-04-01

    Benzo[a]pyrene (BaP) is an environmental contaminant produced during incomplete combustion of organic material that is well known as a mutagenic and carcinogenic toxin. There are few studies addressing the molecular and cellular basis of behavioural alterations related to BaP exposure. The aim of this study was to evaluate the effect of subchronic oral administration of BaP on behavioral and neurochemical parameters. Wistar male rats received BaP (2 mg/kg) or corn oil (control), once a day for 28 days (n = 12/group). Spontaneous locomotor activity and short- and long-term memories were evaluated. Glial fibrillary acid protein and S100B content in the hippocampus, serum and CSF were measured using ELISA and total and phosphorylated forms of mitogen activated protein kinases (MAPKs) named extracellular signal-regulated kinases 1 and 2, p38(MAPK) and c-Jun amino-terminal kinases 1 and 2, in the hippocampus, were evaluated by western blotting. BaP induced a significant increase on locomotor activity and a decrease in short-term memory. S100B content was increased significantly in cerebrospinal fluid. BaP induced a decrease on ERK2 phosphorylation in the hippocampus. Thus, BaP subchronic treatment induces an astroglial response and impairs both motor and cognitive behavior, with parallel inhibition of ERK2, a signaling enzyme involved in the hippocampal neuroplasticity. All these effects suggest that BaP neurotoxicity is a concern for environmental pollution. PMID:24584819

  6. Modulation of benzo[a]pyrene induced immunotoxicity in mice actively immunized with a B[a]P-diphtheria toxoid conjugate.

    Science.gov (United States)

    Schellenberger, Mario T; Grova, Nathalie; Willième, Stéphanie; Farinelle, Sophie; Prodhomme, Emmanuel J F; Muller, Claude P

    2009-10-01

    Benzo[a]pyrene (B[a]P) is a small molecular weight carcinogen and the prototype of polycyclic aromatic hydrocarbons (PAHs). While these compounds are primarily known for their carcinogenicity, B[a]P and its metabolites are also toxic for mammalian immune cells. To develop a prophylactic immune strategy against detrimental effects of B[a]P, we have immunized mice with a B[a]P-diphtheria toxoid conjugate vaccine. We showed that high levels of antibodies against B[a]P and its metabolites modulate the redistribution of these PAHs in the blood. After immunization, increased levels of B[a]P and its metabolites were recovered in the blood. B[a]P significantly suppressed the proliferative response of both T and B cells after a sub-acute administration, an effect that was completely reversed by vaccination. In immunized mice also the immunotoxic effect of B[a]P on IFN-gamma, IL-12, TNF-alpha production and the reduced B cell activation was restored. Finally, our results showed that specific antibodies inhibited the induction of Cyp1a1 by B[a]P in lymphocytes and Cyp1b1 in the liver, enzymes that are known to convert the procarcinogen B[a]P to the ultimate DNA-adduct forming metabolite, a major risk factor of chemical carcinogenesis. Thus, we demonstrate that vaccination with a B[a]P conjugate vaccine based on a carrier protein used in licensed human vaccines reduces immunotoxicity and possibly other detrimental effects associated with B[a]P. PMID:19573549

  7. Effects of benzo[a]pyrene on mitochondrial and nuclear DNA damage in Atlantic killifish (Fundulus heteroclitus) from a creosote-contaminated and reference site

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Dawoon; Cho, Youngeun [Nicholas School of the Environment, Duke University, Durham, NC 27708 (United States); Collins, Leonard B.; Swenberg, James A. [Center for Environmental Health and Susceptibility, Gillings School of Global Public Health, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599 (United States); Di Giulio, Richard T., E-mail: richd@duke.edu [Nicholas School of the Environment, Duke University, Durham, NC 27708 (United States)

    2009-10-19

    Benzo[a]pyrene (BaP) is a known genotoxicant that affects both mitochondrial and nuclear DNA (mtDNA, nDNA). Here, we examined mtDNA and nDNA damage in the Atlantic killifish (Fundulus heteroclitus) from a highly contaminated Superfund site (Elizabeth River, VA, USA) and from a reference site (King's Creek, VA, USA) that were dosed with 10 mg/kg BaP. Using the long amplicon quantitative PCR technique, we observed similar increases in mitochondrial and nuclear DNA damage in King's Creek fish treated with BaP. Killifish from the Elizabeth River showed high levels of basal nDNA and mtDNA damage compared to fish from the reference site, but the level of damage induced due to BaP treatment was much lower in Elizabeth River killifish compared to King's Creek fish. Laboratory-reared offspring from both populations showed increased BaP-induced damage in mtDNA, relative to nDNA. Similar to the adult experiment, the Elizabeth River larvae had higher levels of basal DNA damage than those from the reference site, but were less impacted by BaP exposure. Measurements of oxidative DNA damage (8-oxo-deoxyguanine by LC-MS/MS) showed no differences among treatment groups, suggesting that the majority of DNA damage is from covalent binding of BaP metabolites to DNA. This study shows for the first time that mitochondria can be an important target of BaP toxicity in fish, indicating that BaP exposures could have important energetic consequences. Results also suggest that multi-generational exposures in the wild may lead to adaptations that dampen DNA damage arising from BaP exposure.

  8. Modulation of 17β-estradiol induced estrogenic responses in male goldfish (Carassius auratus) by benzo[a]pyrene and ketoconazole.

    Science.gov (United States)

    Yan, Zhenhua; Lu, Guanghua; Ye, Qiuxia; Liu, Jianchao

    2016-05-01

    The aquatic environment is challenged with complex mixtures of chemicals that may interact biochemically with each other in non-target aquatic organisms through a combination of actions, resulting in unpredictable mixture toxicity. This study focuses on the interactive effects of chemicals, including benzo(a)pyrene (BaP) and ketoconazole (KCZ), on 17β-estradiol (E2)-induced estrogenic responses in male goldfish (Carassius auratus). The possible interactions between BaP or KCZ and E2 were investigated on the expression of cytochromeP4501A (CYP1A, biotransformation enzyme) and on its corresponding catalytic activity 7-ethoxyresorufin-O-deethylase (EROD activity), as well as on the expression of CYP19 (steroidogenic enzyme) and E2 bioaccumulation in liver. Exposure to E2 caused a significant increase in estrogenic responses corresponding with the E2 bioaccumulation. When comparing results to the E2 exposure group, co-exposure to BaP resulted in an increase in the cyp1a mRNA expression and its corresponding EROD activity and a marked decrease in the E2 bioaccumulation, but the expression of aromatase was not altered. Conversely, co-treatment with KCZ significantly suppressed the E2-modulated expression of metabolism and synthesis enzymes, which were accompanied by an increase in the E2 bioaccumulation. These data suggest that the modulation of E2-induced estrogenic responses by BaP and KCZ were correlated to the alterations of E2 bioaccumulation in goldfish, leading to a combination of changes in the capacity of biotransformation and steroidogenesis. The complex interactions between chemicals with different modes of actions highlight the need for caution in determining the safety of combined pollution in the aquatic environment. PMID:26825522

  9. Metabolic enzyme activities, metabolism-related genes expression and bioaccumulation in juvenile white shrimp Litopenaeus vannamei exposed to benzo[a]pyrene.

    Science.gov (United States)

    Ren, Xianyun; Pan, Luqing; Wang, Lin

    2014-06-01

    The purpose of this study was to investigate the impact of benzo[a]pyrene (BaP) on metabolic detoxification system and bioaccumulation of white shrimp Litopenaeus vannamei. In this study, juvenile white shrimp L. vannamei were exposed for 21 days at four different concentrations of 0, 0.03, 0.3 and 3μg/L. Detoxification enzyme activities of phase I (aryl hydrocarbon hydroxylase (AHH), 7-ethoxyresorufin O-deethylase (EROD), epoxide hydrolase (EH)) and phase II (glutathione-S-transferase (GST), sulfotransferase (SULT), uridine diphosphate glucuronyl transferase (UGT)) were determined, and results showed that all the detoxification enzyme activities increased in a dose-dependent manner except for the low BaP exposure. Transcription of genes was detected and measured by real-time RT-PCR. It showed that at day six BaP increased cytochrome P450 (CYP) 1A1, GST, SULT visa aryl hydrocarbon receptor (AhR) mRNA expression in a dose-dependent manner, which suggests that they could be potential targets of BaP that disrupt the detoxification system. The consistency of their responses to BaP exposure implies that AhR action may be involved in invertebrate CYP regulation. Additionally, BaP bioaccumulation increased rapidly first and showed an incoming plateau. Besides, the enzyme activities and bioaccumulation in the hepatopancreas were higher than those in the gills. These results will not only provide information on BaP metabolic mechanism for this species, but also scientific data for pollution monitoring. PMID:24636950

  10. Fullerene inhibits benzo(a)pyrene Efflux from Cyprinus carpio hepatocytes by affecting cell membrane fluidity and P-glycoprotein expression.

    Science.gov (United States)

    Chen, Qiqing; Hu, Xialin; Wang, Rui; Yuan, Jin; Yin, Daqiang

    2016-05-01

    P-Glycoprotein (P-gp) can protect cells by pumping out toxic compounds, and has been found widely expressed in fish tissues. Here, we illustrate the P-gp efflux ability for benzo(a)pyrene (BaP) in the hepatocytes of common carp (Cyprinus carpio) after exposing to fullerene aqueous suspension (nC60). The results revealed that nC60 increased the membrane fluidity by decreasing the ratio of saturated to unsaturated fatty acids, and increased the cholesterol contents. These findings, combined with 10-38% and 70-75% down-regulation of P-gp mRNA and protein respectively, suggested that nC60 caused inhibition on P-gp efflux transport system. Therefore, we further investigated the cellular efflux ability for BaP. Results showed unequivocally that nC60 is a potent P-gp inhibitor. The retaining BaP amounts after efflux were elevated by 1.7-2.8 fold during the 10 day exposure. Meanwhile, 5mg/L humic acid (one of the important fractions of natural organic matter, which is ubiquitous in aquatic environment) alleviated the nC60 damage to hepatocytes in terms of oxidative damage, cholesterol increment, and P-gp content reduction; and finally attenuated the suppressed P-gp efflux ability. Collectively, this study provides the first evidence of nC60 toxicity to P-gp functionality in fish and illustrates the possible mechanism of the suppressed P-gp efflux ability for BaP. PMID:26918948

  11. Benzo(apireno em óleos de milho produzidos e comercializados no Brasil Benzo(apyrene in corn oils produced and commercialized in Brazil

    Directory of Open Access Journals (Sweden)

    M. Cecilia de F. TOLEDO

    1998-04-01

    Full Text Available Óleos de milho de diferentes marcas, produzidos e comercializados no Brasil, foram analisados quanto à presença de benzo(apireno (B(aP. A metodologia utilizada envolveu extração com ciclohexano, purificação em coluna de silica gel e determinação por cromatografia líquida de alta eficiência com detector de fluorescência. Todas amostras analisadas mostraram-se contaminadas por B(aP e os níveis determinados variaram entre as diferentes marcas analisadas e entre diferentes lotes de mesma marca, dentro da faixa de 0,85 a 25,17 µg/kg. Entre 49 amostras analisadas no período de dois anos, apenas uma apresentou nível de contaminação por B(aP abaixo do limite referencial de 1 µg/kg.Corn oils from different brands produced and commercialized in Brazil, were analysed for benzo(apyrene B(aP. The methodology involved extraction with cyclohexane, clean-up on silica gel and determination by high performance liquid chromatography with a fluorescence detector All samples analysed showed contamination by B(aP and the levels found varied widely among brands and within different batches of the same brand, in the range of 0.85 to 25.17 µg/kg. One out 49 samples analysed in the period of 2 years presented an amount of B(aP below the referencial limit of 1 µg/kg.

  12. Chemopreventive potential of Triphala (a composite Indian drug) on Benzo(a)pyrene induced forestomach tumorigenesis in murine tumor model system

    International Nuclear Information System (INIS)

    The present work is probably the first report on cancer chemopreventive potential of Triphala, a combination of fruit powder of three different plants namely Terminalia chebula, Terminalia belerica and Emblica officinalis. Triphala is a popular formulation of the Ayurvedic system of medicine. Our findings have shown that Triphala in diet has significantly reduced the benzo(a)pyrene [B(a)P] induced forestomach papillomagenesis in mice. In the short term treatment groups, the tumor incidences were lowered to 77.77% by both doses of Triphala mixed diet. In the case of long-term treatment the tumor incidences were reduced to 66.66% and 62.50% respectively by 2.5% and 5% triphala containing diet. Tumor burden was 7.27±1.16 in the B(a)P treated control group, whereas it reduced to 3.00±0.82 (p<0.005) by 2.5% dose and 2.33 +/- 1.03 (p<0.001) by 5% dose of Triphala. In long-term studies the tumor burden was reduced to 2.17±0.75 (p<0.001) and 2.00±0.71 (p<0.001) by 2.5% and 5% diet of Triphala, respectively. It was important to observe that Triphala was more effective in reducing tumor incidences compared to its individual constituents. Triphala also significantly increased the antioxidant status of animals which might have contributed to the chemoprevention. It was inferred that the concomitant use of multiple agents seemed to have a high degree of chemoprevention potential

  13. Neonatal exposure to benzo[a]pyrene induces oxidative stress causing altered hippocampal cytomorphometry and behavior during early adolescence period of male Wistar rats.

    Science.gov (United States)

    Patel, Bhupesh; Das, Saroj Kumar; Das, Swagatika; Das, Lipsa; Patri, Manorama

    2016-05-01

    Environmental neurotoxicants like benzo[a]pyrene (B[a]P) have been well documented regarding their potential to induce oxidative stress. However, neonatal exposure to B[a]P and its subsequent effect on anti-oxidant defence system and hippocampal cytomorphometry leading to behavioral changes have not been fully elucidated. We investigated the effect of acute exposure of B[a]P on five days old male Wistar pups administered with single dose of B[a]P (0.2 μg/kg BW) through intracisternal mode. Control group was administered with vehicle i.e., DMSO and a separate group of rats without any treatment was taken as naive group. Behavioral analysis showed anxiolytic-like behavior with significant increase in time spent in open arm in elevated plus maze. Further, significant reduction in fall off time during rotarod test showing B[a]P induced locomotor hyperactivity and impaired motor co-ordination in adolescent rats. B[a]P induced behavioral changes were further associated with altered anti-oxidant defence system involving significant reduction in the total ATPase, Na(+) K(+) ATPase, Mg(2+) ATPase, GR and GPx activity with a significant elevation in the activity of catalase and GST as compared to naive and control groups. Cytomorphometry of hippocampus showed that the number of neurons and glia in B[a]P treated group were significantly reduced as compared to naive and control. Subsequent observation showed that the area and perimeter of hippocampus, hippocampal neurons and neuronal nucleus were significantly reduced in B[a]P treated group as compared to naive and control. The findings of the present study suggest that the alteration in hippocampal cytomorphometry and neuronal population associated with impaired antioxidant signaling and mood in B[a]P treated group could be an outcome of neuromorphological alteration leading to pyknotic cell death or impaired differential migration of neurons during early postnatal brain development. PMID:26946409

  14. Comparative metabolism of benzo[a]pyrene by human keratinocytes infected with high-risk human papillomavirus types 16 and 18 as episomal or integrated genomes

    Directory of Open Access Journals (Sweden)

    Neil Trushin

    2012-01-01

    Full Text Available Background: Infection with human papillomavirus (HPV is a critical factor in the development of cervical cancer. Smoking is an additional risk factor. Tobacco smoke carcinogens, such as benzo[a]pyrene (B[a]P, and their cytochrome P450-related metabolites are present in significantly higher levels in the cervical mucus of women smokers than in nonsmokers. We determined the metabolism and P450 expression of B[a]P-treated human keratinocytes infected with HPV-16 or -18. Materials and Methods: Monolayer cultures of uninfected primary human foreskin keratinocytes, human vaginal and cervical keratinocytes carrying episomal genomes of HPV-16 and -18, respectively, and invasive cervical carcinoma cell lines carrying either HPV-16 or -18 genomes integrated into the host DNA, were incubated with 0.1 μM [3H]B[a]P. The resulting oxidative metabolites were analyzed and quantified by radioflow high-performance liquid chromatography. Additionally, all cell lines were incubated with unlabeled 0.1 μM B[a]P for Western blot analysis of cytochrome P450 1A1 and 1B1. Results: Significant enhancement in levels of both detoxification and activation metabolites was found in incubations with all types of HPV-infected cells compared with control incubations (P < 0.05. The highest capacity to metabolize B[a]P was observed with cells containing integrated HPV-18 genomes. Induction of cytochrome 1B1 was observed in HPV-16 and -18 integrated, and in HPV-16 episomal cell types. Conclusions: Both viral genotype and genomic status in the host cell affect B[a]P metabolism and cytochrome P450 1B1 expression. An increase of DNA-damaging metabolites might result from exposure of HPV-infected women to cigarette smoke carcinogens.

  15. Effect of partial hepatectomy on the mutant frequency of benzo(a)pyrene in the liver of C57BL/6 transgenic mice

    International Nuclear Information System (INIS)

    The Big Blue reg-sign transgenic mouse is an in vivo mutation system which permits the study of the role of pharmacodynamic parameters on mutation frequency following xenobiotic exposure. We have studied the effects of cellular proliferation on the frequency of mutations arising in the liver of male C57B1/6 Big Blue reg-sign mice by subjecting the mice to partial hepatectomy following treatment with benzo(a)pyrene (BP). The contribution of cellular proliferation to the induction of mutations and, in turn, to the observed mutant frequency (MF) can be assessed by evaluating the MF in tissues from treated and control animals before and after hepatectomy. Mice (3) were injected with 50 mg/kg of BP in corn oil on three consecutive days, followed by hepatectomy on the fourth day. Three days later (i.e. seven days following the initial BP injection), the animals were sacrificed and the MF in the liver was compared to the MF observed in the same mouse before hepatectomy. Controls were injected with corn oil without BP and were subjected to partial hepatectomy at the same time as the treatment group. The spontaneous MF was not significantly different before (2.3x10-5) and after (1.7x10-5) hepatectomy. Among the BP-treated animals, the MF was 5.7x10-5 and from BP treated mice was 6.1x10-5 suggesting that some lacI mutants arise in E. coli following infection. These data support the notion that turnover of hepatocytes can influence th MF elicited by BP and that bulky adducts remaining in mouse genomic DNA may be packaged and fixed as mutations in E. coli resulting in an increased frequency of sectored mutant plaques

  16. Molecular cloning and differential expression patterns of sigma and omega glutathione S-transferases from Venerupis philippinarum to heavy metals and benzo[a]pyrene exposure

    Institute of Scientific and Technical Information of China (English)

    ZHANG Linbao; WU Huifeng; LIU Xiaoli; CHEN Leilei; WANG Qing; ZHAO Jianmin; YOU Liping

    2012-01-01

    Glutathione S-transferases (GSTs) are a class of enzymes that facilitate the detoxification of xenobiotics,and also play important roles in antioxidant defense.We identified two glutathione S-transferase isoforms (VpGSTS,sigma GST; VpGSTO,omega GST) from Venerupis philippinarum by RACE approaches.The open reading frames of VpGSTS and VpGSTO were of 612 bp and 729 bp,encoding 203 and 242 amino acids with an estimated molecular mass of 22.88 and 27.94 kDa,respectively.The expression profiles of VpGSTS and VpGSTO responded to heavy metals and benzo[a]pyrene (B[a]P) cxposure were investigated by quantitative real-time RT-PCR.The expression of VpGSTS and VpGSTO were both rapidly up-regulated,however,they showed differential expression patterns to different toxicants.Cd displayed stronger induction of VpGSTS expression with an approximately 12-fold increase than that of VpGSTO with a maximum 6.4-fold rise.Cu exposure resulted in similar expression patterns for both VpGSTS and VpGSTO For B[a]P exposure,the maximum induction of VpGSTO was approximately two times higher than that of VpGSTS.Altogether,these findings implied the involvement of VpGSTS and VpGSTO in host antioxidant responses,and highlighted their potential as a biomarker to Cd and B[a]P exposure.

  17. Modulation of benzo[a]pyrene induced neurotoxicity in female mice actively immunized with a B[a]P–diphtheria toxoid conjugate

    International Nuclear Information System (INIS)

    Benzo[a]pyrene (B[a]P) is a small molecular weight carcinogen and the prototype of polycyclic aromatic hydrocarbons (PAHs). While these compounds are primarily known for their carcinogenicity, B[a]P and its metabolites are also neurotoxic for mammalian species. To develop a prophylactic immune strategy against detrimental effects of B[a]P, female Balb/c mice immunized with a B[a]P–diphtheria toxoid (B[a]P–DT) conjugate vaccine were sub-acutely exposed to 2 mg/kg B[a]P and behavioral performances were monitored in tests related to learning and memory, anxiety and motor coordination. mRNA expression of the NMDA receptor (NR1, 2A and 2B subunits) involved in the above behavioral functions was measured in 5 brain regions. B[a]P induced NMDA1 expression in three (hippocampus, amygdala and cerebellum) of five brain regions investigated, and modulated NMDA2 in two of the five brain regions (frontal cortex and cerebellum). Each one of these B[a]P-effects was reversed in mice that were immunized against this PAH, with measurable consequences on behavior such as anxiety, short term learning and memory. Thus active immunization against B[a]P with a B[a]P–DT conjugate vaccine had a protective effect and attenuated the pharmacological and neurotoxic effects even of high concentrations of B[a]P. - Highlights: • B[a]P-antibodies attenuated B[a]P induced NMDA expression in several brain regions. • B[a]P had measurable consequences on anxiety, short term learning and memory. • B[a]P immunization attenuated the pharmacological and neurotoxic effects of B[a]P. • Vaccination may also provide some protection against chemical carcinogenesis

  18. Effects of benzo[a]pyrene on mitochondrial and nuclear DNA damage in Atlantic killifish (Fundulus heteroclitus) from a creosote-contaminated and reference site

    International Nuclear Information System (INIS)

    Benzo[a]pyrene (BaP) is a known genotoxicant that affects both mitochondrial and nuclear DNA (mtDNA, nDNA). Here, we examined mtDNA and nDNA damage in the Atlantic killifish (Fundulus heteroclitus) from a highly contaminated Superfund site (Elizabeth River, VA, USA) and from a reference site (King's Creek, VA, USA) that were dosed with 10 mg/kg BaP. Using the long amplicon quantitative PCR technique, we observed similar increases in mitochondrial and nuclear DNA damage in King's Creek fish treated with BaP. Killifish from the Elizabeth River showed high levels of basal nDNA and mtDNA damage compared to fish from the reference site, but the level of damage induced due to BaP treatment was much lower in Elizabeth River killifish compared to King's Creek fish. Laboratory-reared offspring from both populations showed increased BaP-induced damage in mtDNA, relative to nDNA. Similar to the adult experiment, the Elizabeth River larvae had higher levels of basal DNA damage than those from the reference site, but were less impacted by BaP exposure. Measurements of oxidative DNA damage (8-oxo-deoxyguanine by LC-MS/MS) showed no differences among treatment groups, suggesting that the majority of DNA damage is from covalent binding of BaP metabolites to DNA. This study shows for the first time that mitochondria can be an important target of BaP toxicity in fish, indicating that BaP exposures could have important energetic consequences. Results also suggest that multi-generational exposures in the wild may lead to adaptations that dampen DNA damage arising from BaP exposure.

  19. The ERCC2/XPD Lys751Gln polymorphism affects DNA repair of benzo[a]pyrene induced damage, tested in an in vitro model.

    Science.gov (United States)

    Xiao, Sha; Cui, Su; Lu, Xiaobo; Guan, Yangyang; Li, Dandan; Liu, Qiufang; Cai, Yuan; Jin, Cuihong; Yang, Jinghua; Wu, Shengwen; van der Straaten, Tahar

    2016-08-01

    Nucleotide excision repair (NER) is an important defense mechanism of the body to exogenous carcinogens and mutagens, such as benzo[a]pyrene (B[a]P). Genetic polymorphisms in ERCC2/XPD, a critical element in NER, are thought to be associated with individual's cancer susceptibility. Although ERCC2/XPD Lys751Gln (rs13181) is the most studied polymorphism, the impact of this polymorphism on DNA repair capacity to carcinogen remains unclear. In the present study, cDNA clones carrying different genotypes of ERCC2/XPD (Lys751Gln) were introduced into an ERCC2/XPD deficient cell line (UV5) in a well-controlled biological system. After B[a]P treatment, cell growth inhibition rates and DNA damage levels in all cells were detected respectively. As expected, we found that the DNA repair capacity in UV5 cells was restored to levels similar to wildtype parent AA8 cells upon introduction of the cDNA clone of ERCC2/XPD (Lys751). Interestingly, after B[a]P treatment, transfected cells expressing variant ERCC2/XPD (751Gln) showed an enhanced cellular sensitivity and a diminished DNA repair capacity. The wildtype genotype AA (Lys) was found to be associated with a higher DNA repair capacity as compared to its polymorphic genotype CC (Gln). These data indicate that ERCC2/XPD Lys751Gln polymorphism affects DNA repair capacity after exposure to environmental carcinogens such as B[a]P in this well-controlled in vitro system and could act as a biomarker to increase the predictive value to develop cancer. PMID:27139774

  20. Modulation of benzo[a]pyrene induced neurotoxicity in female mice actively immunized with a B[a]P–diphtheria toxoid conjugate

    Energy Technology Data Exchange (ETDEWEB)

    Schellenberger, Mario T.; Grova, Nathalie; Farinelle, Sophie; Willième, Stéphanie [Institute of Immunology, Centre de Recherche Public de la Santé/Laboratoire National de Santé, 20A rue Auguste Lumière, L-1950 Luxembourg, Grand-Duchy of Luxembourg (Luxembourg); Schroeder, Henri [University of Nancy, URAFPA, INRA UC340, F-54500 Vandoeuvre-lès-Nancy (France); Muller, Claude P., E-mail: claude.muller@crp-sante.lu [Institute of Immunology, Centre de Recherche Public de la Santé/Laboratoire National de Santé, 20A rue Auguste Lumière, L-1950 Luxembourg, Grand-Duchy of Luxembourg (Luxembourg)

    2013-09-01

    Benzo[a]pyrene (B[a]P) is a small molecular weight carcinogen and the prototype of polycyclic aromatic hydrocarbons (PAHs). While these compounds are primarily known for their carcinogenicity, B[a]P and its metabolites are also neurotoxic for mammalian species. To develop a prophylactic immune strategy against detrimental effects of B[a]P, female Balb/c mice immunized with a B[a]P–diphtheria toxoid (B[a]P–DT) conjugate vaccine were sub-acutely exposed to 2 mg/kg B[a]P and behavioral performances were monitored in tests related to learning and memory, anxiety and motor coordination. mRNA expression of the NMDA receptor (NR1, 2A and 2B subunits) involved in the above behavioral functions was measured in 5 brain regions. B[a]P induced NMDA1 expression in three (hippocampus, amygdala and cerebellum) of five brain regions investigated, and modulated NMDA2 in two of the five brain regions (frontal cortex and cerebellum). Each one of these B[a]P-effects was reversed in mice that were immunized against this PAH, with measurable consequences on behavior such as anxiety, short term learning and memory. Thus active immunization against B[a]P with a B[a]P–DT conjugate vaccine had a protective effect and attenuated the pharmacological and neurotoxic effects even of high concentrations of B[a]P. - Highlights: • B[a]P-antibodies attenuated B[a]P induced NMDA expression in several brain regions. • B[a]P had measurable consequences on anxiety, short term learning and memory. • B[a]P immunization attenuated the pharmacological and neurotoxic effects of B[a]P. • Vaccination may also provide some protection against chemical carcinogenesis.

  1. Seasonal variation of benzo(a)pyrene in the Spanish airborne PM10. Multivariate linear regression model applied to estimate BaP concentrations

    International Nuclear Information System (INIS)

    The estimation of benzo(a)pyrene (BaP) concentrations in ambient air is very important from an environmental point of view especially with the introduction of the Directive 2004/107/EC and due to the carcinogenic character of this pollutant. A sampling campaign of particulate matter less or equal than 10 microns (PM10) carried out during 2008-2009 in four locations of Spain was collected to determine experimentally BaP concentrations by gas chromatography mass-spectrometry mass-spectrometry (GC-MS-MS). Multivariate linear regression models (MLRM) were used to predict BaP air concentrations in two sampling places, taking PM10 and meteorological variables as possible predictors. The model obtained with data from two sampling sites (all sites model) (R2 = 0.817, PRESS/SSY = 0.183) included the significant variables like PM10, temperature, solar radiation and wind speed and was internally and externally validated. The first validation was performed by cross validation and the last one by BaP concentrations from previous campaigns carried out in Zaragoza from 2001-2004. The proposed model constitutes a first approximation to estimate BaP concentrations in urban atmospheres with very good internal prediction (QCV2=0.813, PRESS/SSY = 0.187) and with the maximal external prediction for the 2001-2002 campaign (Qext2=0.679 and PRESS/SSY = 0.321) versus the 2001-2004 campaign (Qext2=0.551, PRESS/SSY = 0.449).

  2. Uncertainty evaluation for the quantification of low masses of benzo[a]pyrene: Comparison between the Law of Propagation of Uncertainty and the Monte Carlo method.

    Science.gov (United States)

    Sega, Michela; Pennecchi, Francesca; Rinaldi, Sarah; Rolle, Francesca

    2016-05-12

    A proper evaluation of the uncertainty associated to the quantification of micropollutants in the environment, like Polycyclic Aromatic Hydrocarbons (PAHs), is crucial for the reliability of the measurement results. The present work describes a comparison between the uncertainty evaluation carried out according to the GUM uncertainty framework and the Monte Carlo (MC) method. This comparison was carried out starting from real data sets obtained from the quantification of benzo[a]pyrene (BaP), spiked on filters commonly used for airborne particulate matter sampling. BaP was chosen as target analyte as it is listed in the current European legislation as marker of the carcinogenic risk for the whole class of PAHs. MC method, being useful for nonlinear models and when the resulting output distribution for the measurand is non-symmetric, can particularly fit the cases in which the results of intrinsically positive quantities are very small and the lower limit of a desired coverage interval, obtained according to the GUM uncertainty framework, can be dramatically close to zero, if not even negative. In the case under study, it was observed that the two approaches for the uncertainty evaluation provide different results for BaP masses in samples containing different masses of the analyte, MC method giving larger coverage intervals. In addition, in cases of analyte masses close to zero, the GUM uncertainty framework would give even negative lower limit of uncertainty coverage interval for the measurand, an unphysical result which is avoided when using MC method. MC simulations, indeed, can be configured in a way that only positive values are generated thus obtaining a coverage interval for the measurand that is always positive. PMID:27114218

  3. Dose-Response on the Chemopreventive Effects of Sarcophine-Diol on UVB-Induced Skin Tumor Development in SKH-1 Hairless Mice

    Directory of Open Access Journals (Sweden)

    Chandradhar Dwivedi

    2012-09-01

    Full Text Available Sarcophine-diol (SD is a lactone ring-opened analogue of sarcophine. It has shown chemopreventive effects on chemically-induced skin tumor development in female CD-1 mice, as well as in a UVB-induced skin tumor development model in hairless SKH-1 mice at a dose of 30 μg SD applied topically and 180 mJ/cm2 UVB. The objective of this study was to determine the dose-response on the chemopreventive effects of SD on SKH-1 hairless mice when exposed to a UVB radiation dose of 30 mJ/cm2. This UVB dose better represents chronic human skin exposure to sunlight leading to skin cancer than previous studies applying much higher UVB doses. Carcinogenesis was initiated and promoted by UVB radiation. Female hairless SKH-1 mice were divided into five groups. The control group was topically treated with 200 μL of acetone (vehicle, and the SD treatment groups were topically treated with SD (30 μg, 45 μg, and 60 μg dissolved in 200 μL of acetone 1 h before UVB radiation (30 mJ/cm2. The last group of animals received 60 μg SD/200 μL acetone without UVB exposure. These treatments were continued for 27 weeks. Tumor multiplicity and tumor volumes were recorded on a weekly basis for 27 weeks. Weight gain and any signs of toxicity were also closely monitored. Histological characteristics and the proliferating cell nuclear antigen (PCNA were evaluated in the mice skin collected at the end of the experiment. The dose-response study proved a modest increase in chemopreventive effects with the increase in SD dose. SD reduced the number of cells positively stained with PCNA proliferation marker in mice skin. The study also showed that SD application without UVB exposure has no effect on the structure of skin. The results from this study suggest that broader range doses of SD are necessary to improve the chemopreventive effects.

  4. Response of detoxification gene mRNA expression and selection of molecular biomarkers in the clam Ruditapes philippinarum exposed to benzo[a]pyrene

    International Nuclear Information System (INIS)

    Benzo[a]pyrene (B[a]P) has a high carcinogenic potential. B[a]P concentrations and molecular biomarkers (mRNA expressions of Pgp, AhR, CYP4, CYP414A1, GST-pi, GST-S2, Cu/Zn-SOD and Mn-SOD) were assayed in gills and digestive glands of the clam Ruditapes philippinarum exposed to 0.03, 0.3 and 3 μg/L B[a]P for 21 days and then exposed to natural seawater for 15 days. Results showed that B[a]P was rapidly accumulated in and then eliminated from tissues of the clams. All gene mRNA expressions in the treated groups were induced significantly with the exception of CYP414A1 and Cu/Zn-SOD in the 0.03 μg/L B[a]P group. According to correlation analysis, mRNA expressions of AhR, GST-pi and Mn-SOD in gills and GST-pi in digestive glands had good correlations with B[a]P concentrations and could be used as molecular biomarkers of B[a]P exposure. This study investigated the molecular response of the genes mentioned above and selected useful molecular biomarkers for B[a]P pollution monitoring. - Highlights: • We measured B[a]P contents and mRNA expressions of eight different kinds of genes. • More B[a]P accumulated in digestive glands than in gills. • Most gene mRNA expressions in the treated groups were induced significantly. • AhR, GST-pi and Mn-SOD mRNA expressions in gills could be used as useful biomarkers. • GST-pi mRNA expression in digestive glands could be used as a useful biomarker. - mRNA expressions of AhR, GST-pi and Mn-SOD in gills and GST-pi in digestive glands of the clams are useful molecular biomarkers of B[a]P exposure

  5. Effects of 2,3,7,8-TCDD and benzo[a]pyrene on modulating vitellogenin expression in primary culture of crucian carp (Carassius auratus) hepatocytes

    Institute of Scientific and Technical Information of China (English)

    LIANG Yong; C. K. C. Wong; XU Ying; M. H. Wong

    2004-01-01

    Vitellogenin (Vtg) is the precursor of yolk protein. Its expression and secretion are estrogen-regulated and are crucial for oocyte maturation. An in vitro xenoestrogen screening model was established by measuring Vtg induction in cultured primary hepatocytes from crucian carp. Vtg production was detected by biotin-avidin sandwich ELISA method while Vtg and cytochrome P4501A1 (CYP1A1) mRNA induction were measured by semi- quantitative PCR-primer dropping technique. Vtg and Vtg mRNA were dose-dependently induced by diethylstilbestrol (DES, 0.2-200 ng/mL) in hepatocytes of crucian carp. Co-treatment of the DES-induced hepatocytes with either 2,3,7,8-TCDD (TCDD, 0.1-4 pg/mL) or benzo[a]pyrene (B[a]P, 5-1000 ng/mL) resulted in a reduction of Vtg production and an increment of CYP1A1 mRNA expression both in a dose dependent manner, indicating the anti-estro-genic effects of the compounds. However, at lower tested concentrations, TCDD (0.1, 0.2 pg/mL), B[a]P (5 ng/mL) seemed to have a potentiating effect on Vtg expression and secretion, although by their own these compounds had no observable estrogenic effect on Vtg induction. Tamoxifen (a selective estrogen receptor modulators, 1 nmol/L-1 μmol/L), and β-naphtho-flavone (β-NF, an aryl hydrocarbon receptor inducing compounds, 2.5-1000 ng/mL) also were employed to study the possible interactions in DES-induced Vtg expression. In co-treatment of the DES-induced hepatocytes with β-NF or tamoxifen, the decrease in Vtg production did parallel induction of CYP1A1 for β-NF, but tamoxifen inhibited Vtg induction did not parallel induced CYP1A1 expression in all test concentrations. On the contrary, it was found that in co-treatment of the TCDD-induced hepatocytes with DES, TCDD induced CYP1A1 mRNA production was inhibited by DES also. These results implicated a possible cross talk between estrogen receptor- and aryl hydrocarbon receptor-mediated pathways in the hepatocytes.

  6. The impact of TiO2 nanoparticles on uptake and toxicity of benzo(a)pyrene in the blue mussel (Mytilus edulis).

    Science.gov (United States)

    Farkas, J; Bergum, S; Nilsen, E W; Olsen, A J; Salaberria, I; Ciesielski, T M; Bączek, T; Konieczna, L; Salvenmoser, W; Jenssen, B M

    2015-04-01

    Nanoparticles are emerging contaminants of concern. Knowledge on their environmental impacts is scarce, especially on their interactive effects with other contaminants. In this study we investigated effects of titanium dioxide nanoparticles (TiO2NP) on the blue mussel (Mytilus edulis) and determined their influence on the bioavailability and toxicity of benzo(a)pyrene (B(a)P), a carcinogenic polyaromatic hydrocarbon (PAH). Blue mussels were exposed to either TiO2NP (0.2 and 2.0 mg L(-1)) or B(a)P (20 μg L(-1)) and to the respective combinations of these two compounds. Aqueous contaminant concentrations, the uptake of Ti and B(a)P into mussel soft tissue, effects on oxidative stress and chromosomal damage were analyzed. The uncoated TiO2NP agglomerated rapidly in the seawater. The presence of TiO2NP significantly reduced the bioavailability of B(a)P, shown by lowered B(a)P concentrations in exposure tanks and in mussel tissue. The activities of antioxidant enzyme superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were impacted by the various exposure regimes, indicating oxidative stress in the contaminant exposure groups. While SOD activity was increased only in the 0.2TiO2NP exposure group, CAT activity was enhanced in both combined exposure groups. The GPx activity was increased only in the groups exposed to the two single compounds. In hemocytes, increased chromosomal damage was detected in mussels exposed to the single compounds, which was further increased after exposure to the combination of compounds. In this study we show that the presence of TiO2NP in the exposure system reduced B(a)P uptake in blue mussels. However, since most biomarker responses did not decrease despite of the lower B(a)P uptake in combined exposures, the results suggest that TiO2NP can act as additional stressor, or potentially alters B(a)P toxicity by activation. PMID:25574974

  7. DNA adducts, benzo(a)pyrene monooxygenase activity, and lysosomal membrane stability in Mytilus galloprovincialis from different areas in Taranto coastal waters (Italy)

    International Nuclear Information System (INIS)

    The aim of this study was to investigate the impact of environmental pollution at different stations along the Taranto coastline (Ionian Sea, Puglia, Italy) using several biomarkers of exposure and the effect on mussels, Mytilus galloprovincialis, collected in October 2001 and October 2002. Five sampling sites were compared with a 'cleaner' reference site in the Aeronautics Area. In this study we also investigated the differences between adduct levels in gills and digestive gland. This Taranto area is the most significant industrial settlement on the Ionian Sea known to be contaminated by polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls, heavy metals, etc. Exposure to PAHs was evaluated by measuring DNA adduct levels and benzo(a)pyrene monooxygenase activity (B(a)PMO); DNA adducts were analyzed by 32P-postlabeling with nuclease P1 enhancement in both gills and digestive glands to evaluate differences between DNA adduct levels in the two tissues. B(a)PMO was assayed in the microsomal fraction of the digestive glands as a result of the high expression of P450-metabolizing enzymes in this tissue. Lysosomal membrane stability, a potential biomarker of anthropogenic stress, was also evaluated in the digestive glands of mussels, by measuring the latent activity of β-N-acetylhexosaminidase. Induction of DNA adducts was evident in both tissues, although the results revealed large tissue differences in DNA adduct formation. In fact, gills showed higher DNA adduct levels than did digestive gland. No significant differences were found in DNA adduct levels over time, with both tissues providing similar results in both years. DNA adduct levels were correlated with B(a)PMO activity in digestive gland in both years (r=0.60 in 2001; r=0.73 in 2002). Increases were observed in B(a)PMO activity and DNA adduct levels at different stations; no statistical difference was observed in B(a)PMO activity over the two monitoring campaigns. The membrane labilization period

  8. Sources for PM air pollution in the Po Plain, Italy: I. Critical comparison of methods for estimating biomass burning contributions to benzo(a)pyrene

    Science.gov (United States)

    Belis, C. A.; Cancelinha, J.; Duane, M.; Forcina, V.; Pedroni, V.; Passarella, R.; Tanet, G.; Douglas, K.; Piazzalunga, A.; Bolzacchini, E.; Sangiorgi, G.; Perrone, M.-G.; Ferrero, L.; Fermo, P.; Larsen, B. R.

    2011-12-01

    Particle-bound benzo(a)pyrene (B(a)P) constitutes an air pollution problem in many areas of Europe and has been linked to biomass burning (BB). The present study, conducted in 2007 and 2009 at ten stations in the North Italian Po Plain and Valtelline Valley, examines four methods for the quantification of BB contributions to particle-bound B(a)P using data for 61 predictor compounds in more than 700 ambient PM 10 and PM 2.5 samples. The study was carried out during the heating season - a period of the year with minimal volatilization and atmospheric degradation of B(a)P, which favour source apportionment by receptor modelling. The lowest estimates of the source contribution (SCE) from BB were obtained with the levoglucosan tracer method and multi-linear regression analysis of daily variations in B(a)P concentrations using levoglucosan as the main predictor in combination with a few other predictors including gaseous pollutants and meteorological data. The standard uncertainty of these methods was driven by the uncertainty in the BB emission factor for levoglucosan and mounted to 90% (1 σ). Positive matrix factorization (PMF), using only PAH congeners as predictors, did not produce factors interpretable as emission sources. However, PMF utilizing a broad range of predictor compounds afforded five factors with compositions similar to emission sources. The yielded B(a)P SCEs for BB agreed well with results of chemical mass balance modelling (CMB). Both receptor models gave good predictions (p) of the observed (o) B(a)P concentrations (PMF: p/o = 89 ± 9%, CMB: p/o = 114 ± 17%) with lower uncertainties than the tracer methods (CMB 60%; PMF 54%; 1 σ). The average BB SCEs (mean ± 95% confidence interval) from these models were: 1.0 ± 0.4 ng m -3 at a kerbside in Milan, 1.0 ± 0.2 ng m -3 at six urban background stations in the Po Plain, 0.7 ± 0.3 ng m -3 at two rural background stations in the Po Plain, and 2.1 ± 1.1 ng m -3 at an urban background station in the

  9. Inhibition of aryl hydrocarbon receptor transactivation and DNA adduct formation by CYP1 isoform-selective metabolic deactivation of benzo[a]pyrene

    International Nuclear Information System (INIS)

    Benzo[a]pyrene (BaP), a polyaromatic hydrocarbon produced by the combustion of cigarettes and coke ovens, is a known procarcinogen. BaP activates the aryl hydrocarbon receptor (AhR) and induces the expression of a battery of genes, including CYP1A1, which metabolize BaP to toxic compounds. The possible role of CYP1 enzymes in mediating BaP detoxification or metabolic activation remains to be elucidated. In this study, we assessed the effects of CYP1 enzymes (CYP1A1, CYP1A2 and CYP1B1) on BaP-induced AhR transactivation and DNA adduct formation in HEK293 cells and HepG2 cells. Transfection of CYP1A1 and CYP1B1, but not CYP1A2, suppressed BaP-induced activation of AhR. Expression of CYP1A1 and CYP1A2, but not CYP1B1, inhibited DNA adduct formation in BaP-treated HepG2 cells. These results indicate that CYP1A1 and CYP1B1 play a role in deactivation of BaP on AhR and that CYP1A1 and CYP1A2 are involved in BaP detoxification by suppressing DNA adduct formation. BaP treatment did not induce DNA adduct formation in HEK293 cells, even after transfection of CYP1 enzymes, suggesting that expression of CYP1 enzymes is not sufficient for DNA adduct formation. Lower expression of epoxide hydrolase and higher expression of glutathione S-transferase P1 (GSTP1) and GSTM1/M2 were observed in HEK293 cells compared with HepG2 cells. Dynamic expression of CYP1A1, CYP1A2 and CYP1B1 along with expression of other enzymes such as epoxide hydrolase and phase II enzymes may determine the detoxification or metabolic activation of BaP

  10. Effects of light on the cytotoxicity and genotoxicity of benzo(a)pyrene and an oil refinery effluent in the newt

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, M.; l`Haridon, J. [Universite Paul-Sabatier, Toulouse (France)

    1994-12-31

    The genotoxicity and/or toxicity of benzo(a)pyrene (BaP) were evaluated under different lighting conditions in larvae and embryos of the newt Pleurodeles waltl. Visible light alone, UVA alone, or BaP alone had no toxic effects on the larvae. Conversely, toxic effects were observed in animals exposed to BaP + daylight, or BaP + UVA. The genotoxicity of BaP (50 ppb) was halved by its previous exposure to UVA, and was abolished at the lowest concentration (12.5 ppb). In other experiments, the larvae were exposed alternatively to BaP or Irr BaP (18 hours in dark) and UVA (6 hr in water), every day for 8 days. All animals that had accumulated non-irradiated BaP (50 ppb) showed signs of severe toxicity, and 90% died before the end of the test. On the other hand, irradiated BaP (50 ppb) was a 4-fold less toxic and half as genotoxic as non-irradiated BaP. In addition, exposure of the animals to UVA alone for 4 days prior to treatment with BaP did not affect the genotoxicity or toxicity of this hydrocarbon. In the dark, the embryotoxicity of BaP was markedly attenuated by the presence of the jelly coats. Although UVA alone did not affect growth of the embryos, the toxicity of BaP was enhanced by the combined action of the two agents together or in succession (BaP + UVA or BaP then UVA). Larvae were treated with an oil refinery effluent (EF). At 125 ml/l, EF was not found to be genotoxic in the dark. However, in animals exposed to both EF and UVA, there was a progressive increase in level of micronucleated erythrocytes with increasing duration of daily exposure to UVA. Moreover, the genotoxic potential of irradiated EF + UVA was systematically below that of non-irradiated EF + UVA for all durations of exposure to ultraviolet light. Irradiation of this type of effluent might help reduce its harmful effects on aquatic species. Our results also suggest that metabolic activation is not necessary for hydrocarbons to induce toxic effects. 51 refs., 5 tabs., 3 figs.

  11. Induction and recovery of morphofunctional changes in the intestine of juvenile carnivorous fish (Epinephelus coioides) upon exposure to foodborne benzo[a]pyrene

    International Nuclear Information System (INIS)

    The sublethal toxicity of dietary benzo[a]pyrene, B[a]P, on fish growth and intestinal morphofunctional changes [as measured by epithelial turnover, cell proliferation, hyperplasia, de novo crypt formation and protein absorption efficiency (i.e. expression of proton/peptide co-transporter, PepT-1, on the mucosal brush border)] were studied for the carnivorous orange-spotted grouper (Epinephelus coioides). Juvenile fish were force-fed daily with pellets containing environmentally realistic concentrations of B[a]P (dissolved in corn oil) at 0.25 μg/g body weight (low-dose) and 12.5 μg/g body weight (high-dose) for 4 weeks, followed by a control diet for a further 4 weeks to assess recovery. Although growth inhibition was observed in fish treated with high-dose B[a]P during the exposure period, no mortality was observed throughout the 8-week experiment. Significant hyperplasia of basal enterocytes of mucosal folds was detected shortly after 3-day exposure to the high-dose B[a]P. Moreover, a faster epithelial turnover was measured in the high-dose B[a]P exposed fish at exposure week 1, which was followed by an increase of basal cell proliferation and a reduction of PepT-1 expression at exposure week 2. The formation of de novo crypts, resemblance to the cancer predisposition syndrome 'juvenile polyposis', was significantly higher in the intestine of high-dose treated fish as compared to the control at exposure week 2 and onwards. Abnormal cytoplasmic extrusions were frequently observed in mucosal folds of high-dose fish at exposure week 4. In the low-dose treatment group, only the expression of PepT-1 was significantly reduced at exposure week 2 and an early adaptive response was observed at exposure week 4. Despite all these intestinal disturbances were reversible in fish upon the abatement to dietary B[a]P (within 1-4 weeks), environmental realistic levels of foodborne B[a]P could induce sublethal toxicity to E. coioides, and probably impose potential risk to the

  12. Chemical characterization of fatty acids, alkanes, n-diols and alkyl esters produced by a mixed culture of Trichoderma koningii and Penicillium janthinellum grown aerobically on undecanoic acid, potatoe dextrose and their mixture.

    Science.gov (United States)

    Monreal, Carlos M; Chahal, Amarpreet; Schnitzer, Morris; Rowland, Owen

    2016-05-01

    Little is known about the mixed fungal synthesis of high-value aliphatics derived from the metabolism of simple and complex carbon substrates. Trichoderma koningii and Penicillium janthinellum were fed with undecanoic acid (UDA), potatoe dextrose broth (PDB), and their mixture. Pyrolysis Field Ionization Mass Spectrometry (Py-FIMS) together with (1)H and (13)C Nuclear Magnetic Resonance (NMR) characterized CHCl3 soluble aliphatics in the fungal cell culture. Data from NMR and Py-FIMS analysis were complementary to each other. On average, the mixed fungal species produced mostly fatty acids (28% of total ion intensity, TII) > alkanes (2% of TII) > n-diols (2% of TII) > and alkyl esters (0.8% of TII) when fed with UDA, PDB or UDA+PDB. The cell culture accumulated aliphatics extracellularly, although most of the identified compounds accumulated intracellularly. The mixed fungal culture produced high-value chemicals from the metabolic conversion of simple and complex carbon substrates. PMID:26852878

  13. Tissue differences, dose-response relationship and persistence of DNA adducts in blue mussels (Mytilus edulis L.) exposed to benzo[a]pyrene

    International Nuclear Information System (INIS)

    Baltic Sea blue mussels (Mytilus edulis) were experimentally exposed to the genotoxic model substance benzo[a]pyrene (B[a]P) to study DNA adduct formation. The specific aims were (a) to examine where in the mussels the DNA adducts were formed, in gills or digestive gland; (b) to study the dose-response relationship between B[a]P exposure and DNA adduct formation; and (c) to examine the persistence of the formed adducts. A Scope for growth (SFG) study was also run to compare physiological responses of the mussels with the degree of DNA adduct formation. In an initial dose-response experiment, the mussels were exposed to 0, 5, 50, and 100 μg/l of tritium labelled B[a]P under semi-static conditions for 4 days, and thereafter the bioaccumulation of B[a]P and DNA adduct formation in different tissues was determined using liquid scintillation counting and 32P-postlabelling analysis, respectively. In a following exposure-depuration experiment, mussels were exposed to 17 μg/l of radiolabelled B[a]P under semi-static conditions for 6 days. B[a]P accumulation and DNA adduct formation were determined during the exposure, and B[a]P elimination and persistence of DNA adducts were studied during 28 days of depuration in uncontaminated water. The results revealed large tissue differences in DNA adduct formation. DNA adduct levels were not elevated in the digestive gland of the mussels at any exposure concentration (0-100 μg/l), even though the highest B[a]P tissue concentrations were found in the digestive gland (1.0±0.1 mg B[a]P/g tissue dry wt at 100 μg/l, mean±SE, n=12). DNA adducts were on the other hand formed in the gills, with the highest levels found in mussels exposed to 50 and 100 μg B[a]P/l, and a dose dependent increase in adduct levels (from 1.6 to 5.9 nmol adducts/mol nucleotides) from 0 to 50 μg B[a]P/l. In gills, DNA adduct levels increased with time during the 6-day exposure period in the exposure-depuration experiment, and then persisted for at least 2

  14. Induction of hepatic cytochrome P450 isozymes, benzo(a)pyrene metabolism and DNA binding following exposure to polycyclic aromatic hydrocarbon residues generated during repeated fish fried oil in rats

    International Nuclear Information System (INIS)

    In the present study the effect of repeated fish fried oil (RFFO) and its extract (RFFE) on hepatic cytochrome P450 (CYP) isozymes, benzo(a)pyrene (BP) metabolism and DNA adduct formation was undertaken. HPLC analysis of RFFO showed the presence of several polycyclic aromatic hydrocarbons. CYP in microsomes from control and RFFO-treated animals showed a peak at 450 nm; however, a shift of 2 nm in the SORET region along with significant induction was observed in microsomes prepared from 3-methylcholanthrene (MC)- and RFFE-treated animals. Activities of hepatic ethoxyresorufin-O-deethylase, methoxyresorufin-O-deethylase, aryl hydrocarbon hydroxylase and erythromycin-N-demethylase were found to be significantly (P 3H]-BP to calf thymus DNA. The overall results suggest that exposure to RFFE may induce hepatic CYP isozymes thereby producing enhanced reactive metabolites with a potential to bind with DNA that may result in cancer

  15. Comparison of determining benzo(a)pyrene in vegetable oil by two methods%植物油中苯并(a)芘的检测方法比较研究

    Institute of Scientific and Technical Information of China (English)

    马素换; 汪学德; 刘兵戈

    2014-01-01

    比较高效液相色谱法和气相色谱-质谱联用法测定植物油中苯并(a)芘含量。结果表明,两种方法均采用中性氧化铝固相萃取柱净化油样,平均回收率均大于75%,相对标准偏差均小于8%,检出限分别为0.12μg / kg 和0.40μg / kg,均能满足测定要求。相对来说,高效液相色谱法前处理简便,峰形基线平稳,检出限低,回收率高,更适于植物油中苯并(a)芘含量的测定。%The determinations of benzo(a)pyrene in vegetable oil by high performance liquid chromatog-raphy( HPLC) and gas chromatography - mass spectrometry ( GC - MS) were compared. The results showed that the commercial neutral alumina solid - phase extraction column was employed to purify oil sample by two methods. The average recovery rates and relative standard deviations of two methods were all above 75% and below 8% respectively, and the limits of detection of two methods were 0. 12 μg / kg and 0. 40 μg / kg respectively, which could satisfy the measurement requirements. Relatively, HPLC method had the items of simple pretreatment, smooth baseline of peaks, low limit of detection and high recovery rate, which was more suitable for the determination of benzo(a)pyrene content of vegetable oil.

  16. Gene expression of heat shock protein 70, interleukin-1β and tumor necrosis factor α as tools to identify immunotoxic effects on Xenopus laevis: A dose–response study with benzo[a]pyrene and its degradation products

    International Nuclear Information System (INIS)

    The exposure to benzo[a]pyrene (B[a]P) results in an alteration of immune function in mammals and fish, and the analysis of cytokine mRNA levels has been suggested for predicting the immunomodulatory potential of chemicals. To obtain evidence of the innate immune responses to B[a]P in Xenopus laevis, the present study monitored the mRNA expression of interleukin 1-β (IL-1β), tumor necrosis factor α (TNF-α) and heat shock protein 70 (HSP70) in a laboratorial exposure. Tadpoles exposed to 8.36, 14.64, 89.06 and 309.47 μg/L of B[a]P,were used for detecting hsp70, IL-1β and TNF-α mRNA induction. A dose–response increase in the expression of hsp70 and IL-1β mRNA was found. The results of this study confirmed the use of hsp70 and IL-1β, but not TNF-α, as sensitive indicators of immunotoxic effect of B[a]P in X. laevis. Further research would be required for the validation of these endpoints. - Highlights: ► We study innate immune responses to benzo[a]pyrene in Xenopus laevis. ► mRNA expression of three typical proinflammatory proteins was monitored. ► Heat shock protein 70 mRNA induction showed a concentration/response/time relationship. ► Interleukin 1-β also showed a clear concentration/response relationship. ► Interleukin 1-β and heat shock protein 70 are useful indicators of immunotoxic effects. - The present study analyzed the use of cytokine mRNA levels as an earlier tool for predicting immunotoxicological risks to Xenopus laevis in a dose–response pattern.

  17. Nuclear respiratory factor 1 overexpression attenuates anti-benzopyrene‑7,8-diol-9,10-epoxide-induced S-phase arrest of bronchial epithelial cells.

    Science.gov (United States)

    Wu, Jing; Wang, Yaning; Wo, Da; Zhang, Lijuan; Li, Jue

    2016-05-01

    Nuclear respiratory factor 1 (NRF-1) has important roles in the regulation of several key metabolic genes required for cellular growth and respiration. A previous study by our group indicated that NRF‑1 is involved in mitochondrial dysfunction induced by the environmental pollutant benzo[a]pyrene in the 16HBE human bronchial epithelial cell line. In the present study, it was observed that its genotoxic metabolite, anti‑benzopyrene‑7,8‑diol‑9,10‑epoxide (BPDE), triggered cell cycle arrest in S‑phase in 16HBE cells by activating ataxia-telangiectasia (ATM)/checkpoint kinase (Chk)2 and ATM and Rad3 related (ATR)/Chk1 signaling pathways. NRF‑1 expression was suppressed by BPDE after treatment for 6 h. Flow cytometric analysis revealed that NRF‑1 overexpression attenuated cell cycle arrest in S‑phase induced by BPDE. In line with this result, DNA‑damage checkpoints were activated following NRF‑1 overexpression, as demonstrated by increased phosphorylation of ATM, Chk2 and γH2AX, but not ATR and Chk1, according to western blot analysis. It was therefore indicated that NRF‑1 overexpression attenuated BPDE‑induced S‑phase arrest via the ATM/Chk2 signaling pathway. PMID:27035420

  18. Modulation of the mutagenic effect of benzo[a]pyrene and bleomycin by isoflavone extracts in a rat hepatoma cell line
    Modulação do efeito mutagênico do benzo[a]pireno e bleomicina por extratos de isoflavonas em células de hepatoma de roedor

    OpenAIRE

    Mário Sérgio Mantovani; Juliana Cristina Marcarini; Marcela Stefanini Tsuboy; Mendes Josiane; Lúcia Regina Ribeiro; Clara Beatriz Hoffman-Campo

    2012-01-01

    Epidemiologic studies show that the intake of foods rich in isoflavones (phytoestrogens), such as soybeans, confers protection against various types of cancer, what increases the scientific and popular interest on these compounds. In the present study, phytoestrogens extracts from soybeans were tested for genotoxic potential and modulatory effects on benzo[a]pyrene and bleomycin. Two phytoestrogens were evaluated in vitro, phytoestrogen “A” was supplied by EMBRAPA-Soja, Londrina – PR, and phy...

  19. Synthesis and Crystal Structure of(3S,4R,Z)-3,6-dimethyl-2-(3-methylbut-2-enylidene)-2,3,3a,4,7,7a-hexahydrobenzofuran-3,4-diol

    Institute of Scientific and Technical Information of China (English)

    CHEN Lei; FANG Hu-Biao; HUANG Nian-Yu; WANG Jun-Zhi; ZOU Kun

    2011-01-01

    The title compound of(3S,4R,Z)-3,6-dimethyl-2-(3-methylbut-2-enylidene)-2,3,3a,4,7,7a-hexahydrobenzofuran-3,4-diol,C15H22O3,as a potential gastric cytoprotective agent has been synthesized by the reduction of bisabolangelone in methanol with sodium borohydride.The title compound was characterized by IR and NMR spectra.Meanwhile,the crystal was obtained and determined by X-ray single-crystal diffraction.Crystal data:monoclinic system,space group P21 with a = 6.0692(12),b = 8.9954(18),c = 13.182(3) ,β = 92.59(3)°,V = 718.9(2) 3,Z = 2,F(000) = 272,Dc = 1.156 g/cm3,μ = 0.633 mm-1,R = 0.0362 and wR = 0.1051 for 9490 independent reflections(Rint = 0.0172) and 2461 observed reflections(I 2σ(I)).Intermolecular O-H…O interactions link the molecules into one-dimensional infinite chains running along the b axis,which contributes to the stability of the crystal structure.

  20. Synthesis and Characterization of (Na0.sK0.5)NbO3 (NKN) Thin Films Formed by a Diol-based Sol-gel Process

    Institute of Scientific and Technical Information of China (English)

    SeSastian Wiegandt; Stefan Flege; Olaf Baake; Wolfgang Ensinger

    2012-01-01

    Lead-free (Na0.sK0.5)Nb03 (NKN) thin films were fabricated by spin coating on Pt/Ti/SiO2/Si substrates by a diol-based sol-gel process. Na-acetate, K-acetate, Nb-pentaethoxide and 1,3 propanediol were used to prepare the NKN precursor solution. Thermal analysis showed two characteristic temperatures of 360 and 600℃. Based on these temperatures, a heat treatment program with pyrolysis at 360℃ and calcination at 600℃ after every layer was used. To avoid inhomogeneities and secondary phases, an excess of sodium and potassium was necessary. To evaluate the proper excess amount of sodium and potassium secondary ion mass spectrometry (SIMS) lateral element maps and X-ray diffraction (XRD) patterns were recorded. An excess amount of 20% led to homogeneous distribution of the elements and to single phase perovskite NKN films with random crystal orientation. Scanning electron microscopy (SEMI images showed a pore free surface with 100 nm grains. The leakage current measurements showed a current of lx10-3 A/cm2 at 150 kV/cm.

  1. Determination of boron in waters and in water extracts from wastes by molecular and atomic absorption spectrometry following preliminary boron separation by extraction of its complex with 2-ethylhexane-1,3-diol

    International Nuclear Information System (INIS)

    Two methods for boron determination were developed and tested. The analysis is based on boron separation and preconcentration by extraction from an acid aqueous solution into a chloroform solution of 2-ethylhexane-1,3-diol followed by reextraction into aqueous sodium hydroxide, and subsequent molecular absorption spectroscopic determination with curcumine at 543 nm or atomic absorption spectroscopic determination at 249.8 nm in a nitrous oxide-acetylene flame. The limits of determination (3s criterion) for the two methods are 0.002 and 0.1 mg/l, respectively. The methods were compared with the conventional procedure based on the use of azomethine-H. While the sensitivities of the methods are comparable (the limit of determination for the azomethine-H method is 0.02 mg/l), the proposed methods exhibit a better reliability and are widely applicable to the determination of total boron in all types of water and water extracts. (author) 3 tabs., 37 refs

  2. Synthesis, receptor binding, and tissue distribution of (17α,20E)- and (17α20Z)-21[125I]iodo-11β-methoxy-19-norpregna-1,3,5,(10),20-tetraene-3,17-diol

    International Nuclear Information System (INIS)

    The isomeric (17α,20E)- and (17α,20Z)-21-Iodo-11β-methoxy-19-norpregna-1,3,5,(10),20-tetraene-3,17-diols 1 and 2, respectively, and their no-carrier-added (NCA) [125I]iodo-vinyl analogues were tested for their binding affinity for the estrogen receptor, their relative target tissue retention and their in vivo stability. The (iodovinyl)-11β -methoxygestradiols 3 and 6 were prepared with retention of the configuration about C-20 via destannylation of the tributylstannyl precursors in a similar manner as recently described for the analogous 20E isomer 3 and 20Z isomer 4 of (iodovinyl)estradiol (J. Med. Chem., 31, 1946, 1988). Although both isomeric 11β-methoxyestradiols 1 and 2 showed similar relative binding affinities for estrogen receptors as compared to 3 and 6, the former showed substantial higher receptor-mediated target tissue uptake. Differences in biological properties between the 20E (1) and 20Z isomer (2) are insignificant. However, the 20Z isomer 2 exhibited higher in vivo instability, as judged by iodine uptake in the thyroid, which is in accordance with its relative low chemical stability

  3. Risk analysis of processing methods on benzo(a)pyrene contamination in oil-tea camellia seed oil%加工方式对油茶籽油苯并(a)芘污染的风险分析

    Institute of Scientific and Technical Information of China (English)

    王亚萍; 费学谦; 王开良; 姚小华; 罗凡

    2013-01-01

    根据苯并(a)芘的性质,研究了不同加工方式对油茶籽油苯并(a)芘污染的影响,并提出了控制措施.结果表明,正常压榨的油茶籽油不存在苯并(a)芘污染的风险;油茶籽炒焦容易导致油中苯并(a)芘含量上升;相对于压榨工艺,溶剂浸出工艺制取的油茶籽油苯并(a)芘超标的风险更大,其中浸出溶剂的选择是苯并(a)芘超标与否的关键因素;精炼过程可以有效去除油茶籽油中的苯并(a)芘.避免炒焦和带壳压榨、选用合格的浸出溶剂是控制油茶籽油苯并(a)芘污染的关键.%According to benzo(a)pyrene's properties, the influences of different processing methods on the risk of benzo ( a) pyrene contamination in oil - tea camellia seed oil were studied, and control measures were proposed. The results showed that the oil - tea camellia seed oil extracted by traditional pressing didn't have benzo(a)pyrene contamination risk;excessive frying usually caused high content of benzo(a) pyrene in the oil; compared with pressing process, solvent extraction brought more risk of benzo (a) pyrene in the oil and the selection of solvent was a key factor;refining process could remove benzo (a) pyrene in oil - tea camellia seed oil. In order to prevent benzo( a) pyrene exceeding national standard,excessive frying and in -shell pressing should be avoided and qualified solvent should be selected.

  4. Enhancement of plasma α-fetoprotein, as measured by sandwich-type radioimmunoassay, and induction of γ-glutamyl transpeptidase-positive hepatic cell foci in rats fed benzo[a]pyrene

    International Nuclear Information System (INIS)

    Male Fischer rats were fed semipurified diets containing 0, 1, 100, and 1000 ppM benzo[a]pyrene (BaP) for 6 or 13 wk. Plasma samples were assayed for α-fetoprotein (AFP) by a new sandwich-type radioimmunoassay (RIA) utilizing a special controlled porous-glass solid phase. This procedure is described in detail. Significant AFP elevation (p less than or equal to 0.01) was observed in the highest BaP treatment group after 5 wk of treatment. The 1 and 100 ppM BaP groups exhibited no AFP elevation throughout the study. Liver sections from the 1000 ppM groups had discrete γ-glutamyl transpeptidase (GGT)-positive foci 10 to 20 cells in diameter by the sixth wk. GGT-positive foci were not evident in liver sections from the other treatment groups. Thus a high level of dietary BaP appears to rapidly alter rat liver cells, indicating hepatic neoplasia

  5. Enhanced thyroid hormone breakdown in hepatocytes by mutual induction of the constitutive androstane receptor (CAR, NR1I3) and arylhydrocarbon receptor by benzo[a]pyrene and phenobarbital

    International Nuclear Information System (INIS)

    Xenobiotics may interfere with the hypothalamic-pituitary-thyroid endocrine axis by inducing enzymes that inactivate thyroid hormones and thereby reduce the metabolic rate. This induction results from an activation of xeno-sensing nuclear receptors. The current study shows that benzo[a]pyrene, a frequent contaminant of processed food and activator of the arylhydrocarbon receptor (AhR) activated the promoter and induced the transcription of the nuclear receptor constitutive androstane receptor (CAR, NR1I3) in rat hepatocytes. Likewise, phenobarbital induced the AhR transcription. This mutual induction of the nuclear receptors enhanced the phenobarbital-dependent induction of the prototypic CAR target gene Cyp2b1 as well as the AhR-dependent induction of UDP-glucuronosyltransferases. In both cases, the induction by the combination of both xenobiotics was more than the sum of the induction by either substance alone. By inducing the AhR, phenobarbital enhanced the benzo[a]pyrene-dependent reduction of thyroid hormone half-life and the benzo[a]pyrene-dependent increase in the rate of thyroid hormone glucuronide formation in hepatocyte cultures. CAR ligands might thus augment the endocrine disrupting potential of AhR activators by an induction of the AhR

  6. Antimutagenic activity of cashew apple (Anacardium occidentale Sapindales, Anacardiaceae fresh juice and processed juice (cajuína against methyl methanesulfonate, 4-nitroquinoline N-oxide and benzo[a]pyrene

    Directory of Open Access Journals (Sweden)

    Ana Amelia Melo-Cavalcante

    2008-01-01

    Full Text Available Cashew apple juice (CAJ, produced from the native Brazilian cashew tree (Anacardium occidentale, and has been reported to have antibacterial, antifungal, antitumor, antioxidant and antimutagenic properties. Both the fresh unprocessed juice and the processed juice (cajuína in Portuguese has been shown to consist of a complex mixture containing high concentrations of anacardic and ascorbic acids plus several carotenoids, phenolic compounds and metals. We assessed both types of juice for their antimutagenic properties against the direct mutagens methyl methanesulfonate (MMS and 4-nitroquinoline-N-oxide (4-NQO and the indirect mutagen benzo[a]pyrene (BaP using pre-treatment, co-treatment and post-treatment assays with Salmonella typhimurium strains TA100, TA102, and TA97a. In pre-treatment experiments with strains TA100 and TA102 the fresh juice showed high antimutagenic activity against MMS but, conversely, co-treatment with both juices enhanced MMS mutagenicity and there was an indication of toxicity in the post-treatment regime. In pre-, co-, and post-treatments with TA97a as test strain, antimutagenic effects were also observed against 4-NQO and BaP. These results suggest that both fresh and processed CAJ can protect the cells against mutagenesis induced by direct and indirect mutagens.

  7. Benzo(a)pyrene induces oxidative stress, pro-inflammatory cytokines, expression of nuclear factor-kappa B and deregulation of wnt/beta-catenin signaling in colons of BALB/c mice.

    Science.gov (United States)

    Ajayi, Babajide O; Adedara, Isaac A; Farombi, Ebenezer O

    2016-09-01

    The incidence of colonic toxicity has been epidemiologically linked to the consumption of foods contaminated with benzo(a)pyrene (B[a]P). The present study investigated the effects of B[a]P on biomarkers of oxidative stress, inflammation and wnt-signaling in colon of BALB/c mice following exposure to 62.5, 125 and 250 mg/kg of B[a]P for 7 days by oral gavage. Exposure to B[a]P significantly decreased the colonic antioxidant enzymes activities and glutathione level with concomitant significant increase in myeloperoxidase activity, nitric oxide and lipid peroxidation levels. Colon histopathology results showed treatment-related lesions characterized by atrophy, mucosal ulceration and gland erosion in the B[a]P-treated mice. Immunohistochemistry analysis showed that B[a]P treatment increased the protein expression of nuclear factor kappa B, pro-inflammatory cytokines namely tumor necrosis factor alpha and interleukin-1β, as well as cyclooxygenase-2 and inducible nitric oxide synthase in the mice colon. Altered canonical wnt-signaling was confirmed by strong diaminobenzidine staining for p38 mitogen activated protein kinase, β-catenin expression and absence of adenomatous polyposis coli following B[a]P administration. The present data highlight that exposure to B[a]P induces colon injury via induction of oxidative and nitrosative stress, inflammatory biomarkers and dsyregulation wnt/β-catenin signaling, thus confirming the role of B[a]P in the pathogenesis of colonic toxicity. PMID:27338711

  8. Induction of benzo[a]pyrene Mono-oxygenase in liver cell culture by the photochemical generation of active oxygen species. Evidence for the involvement of singlet oxygen and the formation of a stable inducing intermediate.

    Science.gov (United States)

    Paine, A J

    1976-07-15

    1. The photochemical generation of excited states of oxygen in liver cell culture by the mild ilumination of culture medium containing riboflavin, results in stimulation of benzo[a]pyrene 3-mono-oxygenase, a cytochrome P-450-linked mono-oxygenase. 2. The same large increase in mono-oxygenase activity was found when medium containing riboflavin was illuminated in the absence of cells and then stored in the dark for 24h before contact with the cells. From this it may be inferred that stimulation is due to the formation of a stable inducer in the culture medium. Further experiments indicate that the stable inducer is due to the photo-oxidation of an amino acid. 3. Evidence that singlet oxygen is responsible for initiating the stimulation of the mono-oxygenase is based on the use of molecules that scavenge particular active oxygen species. Of all the scavengers tested, only those that scavenge single oxygen inhibited the stimulation. 4. A hypothesis is developed to relate the stimulation of the mono-oxygenase by singlet oxygen in cultured cells to the regulation of the cytochrome P-450 enzyme system in vivo. It is suggested that single oxygen generation within cells may be a common factor linking the many structurally diverse inducers of the enzyme system. PMID:962887

  9. Reextraction rays and their use in multicomponent systems of the B2O3-Na2O-H2O-β-diol/solvent type for characteristic of B2O3 reextraction from organic into aqueous phase

    International Nuclear Information System (INIS)

    THE SYSTEM B2O3-Na2O-H2O - β-diol/diluent is studied with the aim of choosing the optimal conditions for the reextraction of B2O3 to the aqueous phase. In order to model the process of the B2O3 transition from the organic to the aqueous phase, a concept ''the reextraction beam'' is introduced by analogy with ''the extraction beam''. The method is exemplified by the isothermal section (25 deg C) of the system Na2O-B2O3-H2O-2.6-dimethyloctanediol-4.6/toluol, which describes the reextration of B2O3 to the aqueous phase from the extracts obtained in the system B2O3-H2O-2.6-dimethyloctanediol-4.6/toluol. The data obtained were plotted on the diagram describing the composition of the ternary system Na2O-H2O-B2O3. The treatment of the extract with the varying amounts of NaOH of the same concentration gives a number of points for the aqueus phase composition, forming a straight line, the so called ''reextraction beam''. A diagram was constructed for each reextraction beam on the basis of experimental data: the degree of reextraction of Er (%) as a function of the molar ratio Na2O/B2/3. The practically complete reextraction of B2O3 is attained at the beams 1-3 at Na2O/B2O3 = 2

  10. The role of repair protein Rad51 in synergistic cytotoxicity and mutagenicity induced by epidermal growth factor receptor inhibitor (Gefitinib, IressaR) and benzo[a]pyrene in human lung cancer

    International Nuclear Information System (INIS)

    Rad51 protein is essential for homologous recombination repair of DNA damage, and is over-expressed in chemo- or radioresistant carcinomas. The polycyclic hydrocarbon carcinogen benzo[a]pyrene (B[a]P) affects MAPKs transduction pathways. Gefitinib (IressaR, ZD1839) is a selective epidermal growth factor receptor tyrosine kinase inhibitor that blocks growth factor-mediated cell proliferation and ERK1/2 activation. We hypothesized that gefitinib enhances B[a]P-mediated cytotoxicity by decreasing ERK1/2 activation. Exposure of human lung cancer cells to gefitinib decreased B[a]P-elicited ERK1/2 activation and induced Rad51 protein expression. Gefitinib and B[a]P co-treatment decreased Rad51 protein stability by triggering degradation via a 26S proteasome-dependent pathway. Expression of constitutive active MKK1/2 vectors (MKK1/2-CA) rescues the decreased ERK1/2 activity, and restores Rad51 protein level and stability under gefitinib and B[a]P co-treatment. Gefitinib enhances B[a]P-induced growth inhibition, cytotoxicity and mutagenicity. Co-treatment with gefitinib and B[a]P can further inhibit cell growth significantly after depletion of endogenous Rad51 by siRad51 RNA transfection. Enhancement of ERK1/2 activation by MKK1-CA expression decrease B[a]P- and gefitinib-induced cytotoxicity, and B[a]P-induced mutagenicity. Rad51 protein protects lung cancer cells from synergistic cytotoxic and mutagenic effects induced by gefitinib and B[a]P. Suppression of Rad51 protein expression may be a novel lung cancer therapeutic modality to overcome drug resistance to gefitinib

  11. Induction of CYP1A1 and CYP1B1 by benzo(k)fluoranthene and benzo(a)pyrene in T-47D human breast cancer cells: Roles of PAH interactions and PAH metabolites

    International Nuclear Information System (INIS)

    The interactions of polycyclic aromatic hydrocarbons (PAH) and cytochromes P450 (CYP) are complex; PAHs are enzyme inducers, substrates, and inhibitors. In T-47D breast cancer cells, exposure to 0.1 to 1 μM benzo(k)fluoranthene (BKF) induced CYP1A1/1B1-catalyzed 17β-estradiol (E2) metabolism, whereas BKF levels greater than 1 μM inhibited E2 metabolism. Time course studies showed that induction of CYP1-catalyzed E2 metabolism persisted after the disappearance of BKF or co-exposed benzo(a)pyrene, suggesting that BKF metabolites retaining Ah receptor agonist activity were responsible for prolonged CYP1 induction. BKF metabolites were shown, through the use of ethoxyresorufin O-deethylase and CYP1A1-promoter-luciferase reporter assays to induce CYP1A1/1B1 in T-47D cells. Metabolites formed by oxidation at the C-2/C-3 region of BKF had potencies for CYP1 induction exceeding those of BKF, whereas C-8/C-9 oxidative metabolites were somewhat less potent than BKF. The activities of expressed human CYP1A1 and 1B1 with BKF as substrate were investigated by use of HPLC with fluorescence detection, and by GC/MS. The results showed that both enzymes efficiently catalyzed the formation of 3-, 8-, and 9-OHBKF from BKF. These studies indicate that the inductive effects of PAH metabolites as potent CYP1 inducers are likely to be additional important factors in PAH-CYP interactions that affect metabolism and bioactivation of other PAHs, ultimately modulating PAH toxicity and carcinogenicity

  12. 对(艹孟)烷-3,8-二醇的合成与应用研究进展%Research Progress on Synthesis and Application of p-Menthane-3,8-diol

    Institute of Scientific and Technical Information of China (English)

    何丽芝; 赵振东; 毕良武; 王鹏

    2012-01-01

    对(艹孟)烷-3,8-二醇是一种具有生物活性的化合物,主要来源于柠檬桉精油,可直接用于香水、杀虫剂和药品等.通常采用化学和生物化学的方法合成对(艹孟)烷-3,8-二醇,以替代从柠檬桉叶油分离得到的天然产品.以香茅醛为原料通过Prins环缩合和水解,或者通过Solanum aviculare悬浮培养方式进行生物转化得到对(艹孟)烷-3,8-二醇;通过薄荷醇的氧化,或者以2-丁烯醛为原料与甲基锂、NaClO2等试剂经过较长步骤也可合成对(艹孟)烷-3,8-二醇.对(艹孟)烷-3,8-二醇可应用于制造驱虫剂、凉味剂、药物或者化妆品的添加剂以及海水防护涂料添加剂等.%p-Menthane-3,8-diol (PMD) is a bioactive compound, which is first found in essential oil of leaves of Eucalyptus citriodora and often used as an active composition for perfume, insecticide, and medicine. It is usually synthesized by chemical or biological approaches instead of the direct isolation from the E. citriodora oil. PMD can be synthesized from citronellal through a prins reaction and a hydration,or be transformed from citronellal through a Solarium avwulare suspension culture. It can also be produced from menthol with an oxidation,or synthesized from 2-butenal by a long step reactions with reagents such as MeIi,NaClO2,etc.PMD can be used as repellent,coolant,pharmaceutical,cosmetics,and coatings.

  13. 注射用磷霉素钠中磷霉素钠二醇物含量测定方法的研究%Study on the determination of fosfomycin sodium diol substance in fosfomycin sodium for injection

    Institute of Scientific and Technical Information of China (English)

    邹宇; 刘珂; 姜雯; 张亚杰; 刘亚威

    2012-01-01

    Objectives;To establish LC - MS/MS and HPLC - RID methods to determine fosfomycin sodium diol substance in fosfomycin sodium for injection, and compare with the method in Chinese Pharmacopoeia to improve the quality control of fosfomycin sodium. Methods: LC - MS/MS method was achieved on Promosil CN column (2S0 mm x4. 6 mm,5 p,m)with mobile phase consisting of 5 mmol · L"1 ammonium acetate solution - methanol (82:18). The analytes were detected in the negative ion mode. Multiple reaction monitoring using the precursor to product ion combinations of m/z 154. 9 ->80. 9 and m/z 120. 9 ->77. 1 was performed to quantify fosfomycin diol substance and the internal standard benzoic acid, respectively. HPLC - RID method was achieved on Agilent Zorbax NH2 column(250 mm x4. 6 mm,5 (xm) utilizing a mobile phase of 10. 89 g · L-1 potassium dihydrogen phosphate solution at the flow rate of 1. 0 mL · min"1. The column temperature was 36℃and the temperature of RID detector was set at 35℃. Results;The LC - MS/MS method;The standard curve was linear in the concentration range of 22. 46 - 359. 4 ng · mL-1. The lower limit of quantification was 4. 492 ng · mL-1,each sample was chromatographed within 5 min. The HPLC - RID method;The standard curve was linear in the concentration range of 0. 104 - 5. 205 mg · mL-1 , the method precision was 0. 7% . Conclusions; The two methods are specific, simple and reliable, and can be applied to quality research and control of fosfomycin sodium for injection.%目的:建立液相色谱串联质谱法和高效液相色谱-示差折光法测定注射用磷霉素钠中的磷霉素钠二醇物含量,并与现行中国药典方法比较,提高对药品的质量控制.方法:液相色谱串联质谱法采用Promosil CN(250 mm×4.6mm,5μm)色谱柱,流动相为5 mmol·L-1醋酸铵-甲醇(82:18),采用(-)ESI电离源,多反应监测(MRM)扫描方式,用于定量分析的离子分别为m/z 154.9→80.9(磷霉素二醇物)和m/z 120.9 →77.1(内标

  14. Cytochrome P450-dependent binding of 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (B[a]P) in murine heart, lung, and liver endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Lizette Granberg, A.; Brunstroem, B.; Brandt, I. [Uppsala Univ. (Sweden). Dept. of Environmental Toxicology

    2000-12-01

    Autoradiography was used to investigate the cellular sites of irreversible binding of {sup 3}H-labelled 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (B[a]P) in mice. Autoradiograms obtained from solvent-extracted tape-sections revealed an even distribution of DMBA- and B[a]P-derived radioactivity in control mice lacking sites of selective binding in the tissues. In mice pretreated with a cytochrome P4501A (CYPIA) inducer, {beta}-naphthoflavone (BNF) or 3,3',4,4', 5-pentachlorobiphenyl (PCB 126), a noticeable accumulation of bound radioactivity was observed in the pulmonary alveolar region. Increased labelling was also observed in heart tissue of induced mice. As demonstrated by microautoradiography of tissues from CYP1A-induced mice treated with {sup 3}H-DMBA or {sup 3}H-B[a]P in vivo, irreversible binding in lung tissue was present in endothelial cells of arteries and veins, in the alveolar septal walls, and in type 2 pneumocytes. In heart tissue, binding was confined to endothelial cells of arteries, capillaries and veins. In liver, binding was found in the hepatocytes as well as in endothelial cells of the portal veins, whereas no binding was seen in endothelial cells of the sinusoids, central veins, or arteries. These findings were confirmed in vitro using {sup 3}H-DMBA-exposed precision-cut slices, indicating that reactive intermediates of DMBA and B(a)P were formed in situ. The addition of the CYP1A inhibitor ellipticine abolished binding in the target endothelial cells. Increased endothelial binding in the lungs and liver of CYP1A-induced mice was concomitant with increased 7-ethoxyresorufin O-deethylase (EROD) and DMBA hydroxylase activity. In heart, endothelial binding was positively correlated with EROD, but not with DMBA hydroxylase. The results suggest that endothelial cells may be targets for CYP-dependent activation of such toxicants as polycyclic aromatic hydrocarbons. Consequently, the possibility that chemically induced

  15. Sustained induction of cytochrome P4501A1 in human hepatoma cells by co-exposure to benzo[a]pyrene and 7H-dibenzo[c,g]carbazole underlies the synergistic effects on DNA adduct formation

    International Nuclear Information System (INIS)

    To gain a deeper insight into the potential interactions between individual aromatic hydrocarbons in a mixture, several benzo[a]pyrene (B[a]P) and 7H-dibenzo[c,g]carbazole (DBC) binary mixtures were studied. The biological activity of the binary mixtures was investigated in the HepG2 and WB-F344 liver cell lines and the Chinese hamster V79 cell line that stably expresses the human cytochrome P4501A1 (hCYP1A1). In the V79 cells, binary mixtures, in contrast to individual carcinogens, caused a significant decrease in the levels of micronuclei, DNA adducts and gene mutations, but not in cell survival. Similarly, a lower frequency of micronuclei and levels of DNA adducts were found in rat liver WB-F344 cells treated with a binary mixture, regardless of the exposure time. The observed antagonism between B[a]P and DBC may be due to an inhibition of Cyp1a1 expression because cells exposed to B[a]P:DBC showed a decrease in Cyp1a1 mRNA levels. In human liver HepG2 cells exposed to binary mixtures for 2 h, a reduction in micronuclei frequency was also found. However, after a 24 h treatment, synergism between B[a]P and DBC was determined based on DNA adduct formation. Accordingly, the up-regulation of CYP1A1 expression was detected in HepG2 cells exposed to B[a]P:DBC. Our results show significant differences in the response of human and rat cells to B[a]P:DBC mixtures and stress the need to use multiple experimental systems when evaluating the potential risk of environmental pollutants. Our data also indicate that an increased expression of CYP1A1 results in a synergistic effect of B[a]P and DBC in human cells. As humans are exposed to a plethora of noxious chemicals, our results have important implications for human carcinogenesis. - Highlights: • B[a]P:DBC mixtures were less genotoxic in V79MZh1A1 cells than B[a]P and DBC alone. • An antagonism between B[a]P and DBC was determined in rat liver WB-F344 cells. • The inhibition of CYP1a1 expression by B[a]P:DBC mixture

  16. Benzo[a]pyrene affects Jurkat T cells in the activated state via the antioxidant response element dependent Nrf2 pathway leading to decreased IL-2 secretion and redirecting glutamine metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Murugaiyan, Jayaseelan; Rockstroh, Maxie; Wagner, Juliane [Department of Proteomics, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Baumann, Sven [Department of Metabolomics, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Schorsch, Katrin [Department of Proteomics, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Trump, Saskia; Lehmann, Irina [Department of Environmental Immunology, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Bergen, Martin von [Department of Proteomics, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Department of Environmental Immunology, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Department of Biotechnology, Chemistry and Environmental Engineering, Aalborg University, Aalborg (Denmark); Tomm, Janina M., E-mail: Janina.tomm@ufz.de [Department of Proteomics, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany)

    2013-06-15

    There is a clear evidence that environmental pollutants, such as benzo[a]pyrene (B[a]P), can have detrimental effects on the immune system, whereas the underlying mechanisms still remain elusive. Jurkat T cells share many properties with native T lymphocytes and therefore are an appropriate model to analyze the effects of environmental pollutants on T cells and their activation. Since environmental compounds frequently occur at low, not acute toxic concentrations, we analyzed the effects of two subtoxic concentrations, 50 nM and 5 μM, on non- and activated cells. B[a]P interferes directly with the stimulation process as proven by an altered IL-2 secretion. Furthermore, B[a]P exposure results in significant proteomic changes as shown by DIGE analysis. Pathway analysis revealed an involvement of the AhR independent Nrf2 pathway in the altered processes observed in unstimulated and stimulated cells. A participation of the Nrf2 pathway in the change of IL-2 secretion was confirmed by exposing cells to the Nrf2 activator tBHQ. tBHQ and 5 μM B[a]P caused similar alterations of IL-2 secretion and glutamine/glutamate metabolism. Moreover, the proteome changes in unstimulated cells point towards a modified regulation of the cytoskeleton and cellular stress response, which was proven by western blotting. Additionally, there is a strong evidence for alterations in metabolic pathways caused by B[a]P exposure in stimulated cells. Especially the glutamine/glutamate metabolism was indicated by proteome pathway analysis and validated by metabolite measurements. The detrimental effects were slightly enhanced in stimulated cells, suggesting that stimulated cells are more vulnerable to the environmental pollutant model compound B[a]P. - Highlights: • B[a]P affects the proteome of Jurkat T cells also at low concentrations. • Exposure to B[a]P (50 nM, 5 μM) did not change Jurkat T cell viability. • Both B[a]P concentrations altered the IL-2 secretion of stimulated cells.

  17. In vivo flow cytometric Pig-a and micronucleus assays: highly sensitive discrimination of the carcinogen/noncarcinogen pair benzo(a)pyrene and pyrene using acute and repeated-dose designs.

    Science.gov (United States)

    Torous, Dorothea K; Phonethepswath, Souk; Avlasevich, Svetlana L; Mereness, Jared; Bryce, Steven M; Bemis, Jeffrey C; Weller, Pamela; Bell, Sara; Gleason, Carol; Custer, Laura L; MacGregor, James T; Dertinger, Stephen D

    2012-07-01

    Combining multiple genetic toxicology endpoints into a single in vivo study, and/or integrating one or more genotoxicity assays into general toxicology studies, is attractive because it reduces animal use and enables comprehensive comparative analysis using toxicity, metabolism, and pharmacokinetic information from the same animal. This laboratory has developed flow cytometric scoring techniques for monitoring two blood-based genotoxicity endpoints-micronucleated reticulocyte frequency and gene mutation at the Pig-a locus-thereby making combination and integration studies practical. The ability to effectively monitor these endpoints in short-term and repeated dosing schedules was investigated with the carcinogen/noncarcinogen pair benzo(a)pyrene (BP) and pyrene (Pyr). Male Sprague-Dawley rats were treated via oral gavage for 3 or 28 consecutive days with several dose levels of Pyr, including maximum tolerated doses. BP exposure was administered by the same route but at one dose level, 250 or 125 mg/kg/day for 3-day and 28-day studies, respectively. Serial blood samples were collected up to Day 45, and were analyzed for Pig-a mutation with a dual labeling method (SYTO 13 in combination with anti-CD59-PE) that facilitated mutant cell frequency measurements in both total erythrocytes and the reticulocyte subpopulation. A mutant cell enrichment step based on immunomagnetic column separation was used to increase the statistical power of the assay. BP induced robust mutant reticulocyte responses by Day 15, and elevated frequencies persisted until study termination. Mutant erythrocyte responses lagged mutant reticulocyte responses, with peak incidences observed on Day 30 of the 3-day study (43-fold increase) and on Day 42 of the 28-day study (171-fold increase). No mutagenic effects were apparent for Pyr. Blood samples collected on Day 4, and Day 29 for the 28-day study, were evaluated for micronucleated reticulocyte frequency. Significant increases in micronucleus

  18. Benzo[a]pyrene affects Jurkat T cells in the activated state via the antioxidant response element dependent Nrf2 pathway leading to decreased IL-2 secretion and redirecting glutamine metabolism

    International Nuclear Information System (INIS)

    There is a clear evidence that environmental pollutants, such as benzo[a]pyrene (B[a]P), can have detrimental effects on the immune system, whereas the underlying mechanisms still remain elusive. Jurkat T cells share many properties with native T lymphocytes and therefore are an appropriate model to analyze the effects of environmental pollutants on T cells and their activation. Since environmental compounds frequently occur at low, not acute toxic concentrations, we analyzed the effects of two subtoxic concentrations, 50 nM and 5 μM, on non- and activated cells. B[a]P interferes directly with the stimulation process as proven by an altered IL-2 secretion. Furthermore, B[a]P exposure results in significant proteomic changes as shown by DIGE analysis. Pathway analysis revealed an involvement of the AhR independent Nrf2 pathway in the altered processes observed in unstimulated and stimulated cells. A participation of the Nrf2 pathway in the change of IL-2 secretion was confirmed by exposing cells to the Nrf2 activator tBHQ. tBHQ and 5 μM B[a]P caused similar alterations of IL-2 secretion and glutamine/glutamate metabolism. Moreover, the proteome changes in unstimulated cells point towards a modified regulation of the cytoskeleton and cellular stress response, which was proven by western blotting. Additionally, there is a strong evidence for alterations in metabolic pathways caused by B[a]P exposure in stimulated cells. Especially the glutamine/glutamate metabolism was indicated by proteome pathway analysis and validated by metabolite measurements. The detrimental effects were slightly enhanced in stimulated cells, suggesting that stimulated cells are more vulnerable to the environmental pollutant model compound B[a]P. - Highlights: • B[a]P affects the proteome of Jurkat T cells also at low concentrations. • Exposure to B[a]P (50 nM, 5 μM) did not change Jurkat T cell viability. • Both B[a]P concentrations altered the IL-2 secretion of stimulated cells.

  19. Sustained induction of cytochrome P4501A1 in human hepatoma cells by co-exposure to benzo[a]pyrene and 7H-dibenzo[c,g]carbazole underlies the synergistic effects on DNA adduct formation

    Energy Technology Data Exchange (ETDEWEB)

    Gábelová, Alena, E-mail: alena.gabelova@savba.sk [Cancer Research Institute, Slovak Academy of Sciences, Vlárska 7, 833 91 Bratislava (Slovakia); Poláková, Veronika [Cancer Research Institute, Slovak Academy of Sciences, Vlárska 7, 833 91 Bratislava (Slovakia); Prochazka, Gabriela [Department of Biosciences and Nutrition, Karolinska Institute, Novum, SE-141 83 Huddinge (Sweden); Department of Medical Epidemiology and Biostatistics, Karolinska Institute, SE-171 77 Stockholm (Sweden); Kretová, Miroslava; Poloncová, Katarína; Regendová, Eva; Luciaková, Katarína [Cancer Research Institute, Slovak Academy of Sciences, Vlárska 7, 833 91 Bratislava (Slovakia); Segerbäck, Dan [Department of Biosciences and Nutrition, Karolinska Institute, Novum, SE-141 83 Huddinge (Sweden)

    2013-08-15

    To gain a deeper insight into the potential interactions between individual aromatic hydrocarbons in a mixture, several benzo[a]pyrene (B[a]P) and 7H-dibenzo[c,g]carbazole (DBC) binary mixtures were studied. The biological activity of the binary mixtures was investigated in the HepG2 and WB-F344 liver cell lines and the Chinese hamster V79 cell line that stably expresses the human cytochrome P4501A1 (hCYP1A1). In the V79 cells, binary mixtures, in contrast to individual carcinogens, caused a significant decrease in the levels of micronuclei, DNA adducts and gene mutations, but not in cell survival. Similarly, a lower frequency of micronuclei and levels of DNA adducts were found in rat liver WB-F344 cells treated with a binary mixture, regardless of the exposure time. The observed antagonism between B[a]P and DBC may be due to an inhibition of Cyp1a1 expression because cells exposed to B[a]P:DBC showed a decrease in Cyp1a1 mRNA levels. In human liver HepG2 cells exposed to binary mixtures for 2 h, a reduction in micronuclei frequency was also found. However, after a 24 h treatment, synergism between B[a]P and DBC was determined based on DNA adduct formation. Accordingly, the up-regulation of CYP1A1 expression was detected in HepG2 cells exposed to B[a]P:DBC. Our results show significant differences in the response of human and rat cells to B[a]P:DBC mixtures and stress the need to use multiple experimental systems when evaluating the potential risk of environmental pollutants. Our data also indicate that an increased expression of CYP1A1 results in a synergistic effect of B[a]P and DBC in human cells. As humans are exposed to a plethora of noxious chemicals, our results have important implications for human carcinogenesis. - Highlights: • B[a]P:DBC mixtures were less genotoxic in V79MZh1A1 cells than B[a]P and DBC alone. • An antagonism between B[a]P and DBC was determined in rat liver WB-F344 cells. • The inhibition of CYP1a1 expression by B[a]P:DBC mixture

  20. DIFFERENCES IN DETECTION OF DNA ADDUCTS IN THE 32P-POSTLABELING ASSAY AFTER EITHER 1-BUTANOL EXTRACTION OR NUCLEASE P1 TREATMENT

    Science.gov (United States)

    The use of nuclease Pl treatment and 1-butanol extraction to increase the sensitivity of the 32P-postlabe1ling assay for DNA adducts have been compared. lthough similar results were obtained with the two methods for standard adducts formed with benzo(a)pyrene diol epoxide I, nucl...

  1. Flow cytometric measurement of the metabolism of benzo [a] pyrene by mouse liver cells in culture

    International Nuclear Information System (INIS)

    The metabolism of benzo[a]pyrene in individual cells was monitored by flow cytometry. The measurements are based on the alterations that occur in the fluorescence emission spectrum of benzo[a]pyrene when it is converted to various metabolities. Using present instrumentation the technique could easily detect 1 x 10/sup 6/ molecules per cells of benzo [a]pyrene and 1 x 10/sup 7/ molecules per cell of the diol epoxide. The analysis of C3H IOT 1/2 mouse fibroblasts growing in culture indicated that there was heterogeneity in the conversion of the parent compound into diol epoxide derivative suggesting that some variation in sensitivity to transformation by benzo[a]pyrene may be due to differences in cellular metabolism

  2. 2,3-Diols versus 3,4-diols in the bean second internode

    Czech Academy of Sciences Publication Activity Database

    Šíša, Miroslav; Swaczynová, Jana; Kohout, Ladislav

    Bialystok : University of Bialystok, 2005, s. 95. [Conference on Isoprenoids /21./. Bialowieza (PL), 23.09.2005-29.09.2005] R&D Projects: GA AV ČR(CZ) IBS4055304 Institutional research plan: CEZ:AV0Z40550506 Keywords : brassinolide analogues * cholestane * internode bioassay Subject RIV: CC - Organic Chemistry

  3. Benzo(a)pyrene-albumin adducts in humans exposed to polycyclic aromatic hydrocarbons in an industrial area of Poland.

    OpenAIRE

    Kure, E H; Andreassen, A; Ovrebø, S; Grzybowska, E; Fiala, Z; Strózyk, M; Chorazy, M; Haugen, A

    1997-01-01

    OBJECTIVES: The interaction of benzo(a)pyrene with serum albumin was measured in an attempt to identify the actual exposure and to evaluate albumin adduct measurements as biomarkers for exposure monitoring. METHODS: Benzo(a)pyrene-diol-epoxide (BPDE)-albumin adducts were measured by competitive enzyme linked immunosorbent assay (ELISA) in plasma of coke oven plant workers from three plants and from people living in a highly industrialised area of Silesia in Poland. Due to the high air concent...

  4. Substituted silane-diol polymers have improved thermal stability

    Science.gov (United States)

    Byrd, J. D.; Curry, J. E.

    1966-01-01

    Organosilicon polymers were synthesized to produce improved physical and chemical properties, including high thermal stability. Of the polymers produced, poly/4, 4 prime-bisoxybi- phenylene/diphenylsilane, formed from bis/anilino/diphenylsilane and p, p prime-biphenol, was found to have the most desirable properties.

  5. Modulation of the mutagenic effect of benzo[a]pyrene and bleomycin by isoflavone extracts in a rat hepatoma cell line Modulação do efeito mutagênico do benzo[a]pireno e bleomicina por extratos de isoflavonas em células de hepatoma de roedor

    Directory of Open Access Journals (Sweden)

    Mário Sérgio Mantovani

    2012-06-01

    Full Text Available Epidemiologic studies show that the intake of foods rich in isoflavones (phytoestrogens, such as soybeans, confers protection against various types of cancer, what increases the scientific and popular interest on these compounds. In the present study, phytoestrogens extracts from soybeans were tested for genotoxic potential and modulatory effects on benzo[a]pyrene and bleomycin. Two phytoestrogens were evaluated in vitro, phytoestrogen “A” was supplied by EMBRAPA-Soja, Londrina – PR, and phytoestrogen “B” was purchased in a local drug store. The methods used were the comet assay (genotoxicity and antigenotoxicity and micronucleus test with cytokinesis block (mutagenicity in rat hepatoma cells (HTC cell. The isoflavones were tested at three concentrations pre-established by the MTT cytotoxicity assay. Both isoflavone extracts showed no genotoxic effects in the comet assay, but showed induction of micronucleus. In the evaluation of the phytoestrogens for a modulatory effect, both phytoestrogens extracts showed antigenotoxicity in the comet assay.Estudos epidemiológicos mostram que a ingestão de alimentos ricos em isoflavonas (fitoestrógenos, como a soja, confere proteção contra vários tipos de câncer, o que aumenta o interesse científico e popular sobre esses compostos. No presente estudo, os fitoestrógenos de extrato de soja foram testados quanto aos efeitos genotóxicos e modulador de benzo [a] pireno e bleomicina. Dois fitoestrogênios foram avaliados in vitro, o fitoestrógenos “A” foi fornecido pela Embrapa-Soja, Londrina - PR, e o fitoestrógenos “B” foi comprado em uma farmácia de manipulação local. Os métodos utilizados foram o teste do Cometa (genotoxicidade e antigenotoxicidade e teste do Micronúcleo com Bloqueio Citocinese (mutagenicidade em células de hepatoma de rato (HTC celulares. As isoflavonas foram testadas em três concentrações pré-estabelecidas pelo ensaio de citotoxidade MTT. Ambos os

  6. Photoinduced electron transfer and fluorescence mechanisms in covalently linked polynuclear aromatic-nucleotide complexes

    Science.gov (United States)

    Geacintov, Nicholas E.; Mao, Bing; France, Luisa L.; Zhao, Rushen; Chen, Junxin; Liu, Tong M.; Ya, Nai-Qi; Margulis, Leonid A.; Sutherland, John C.

    1992-04-01

    The fluorescence of polycyclic aromatic hydrocarbon-nucleic acid complexes is quenched by photoinduced electron transfer mechanisms in aqueous solutions at ambient temperatures. These effects are illustrated with the biologically important compound benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), a mutagenic and carcinogenic metabolite of the environmental pollutant benzo[a]pyrene, which forms covalent mutagenic lesions with 2'-deoxyguanosine (dG) residues in DNA. The dependence of the fluorescence yield and fluorescence decay times of the covalent model adduct (+)-trans- BPDE-N2-dG as a function of temperature and methanol/water composition are described. Because of the sensitivity of the fluorescence of the pyrenyl residue to the polarity of the microenvironment, the magnitude of the fluorescence yield can be used to distinguish between highly hydrophobic (e.g., intercalation) and other more solvent-exposed BPDE- nucleic acid binding sites.

  7. Base substitution mutations induced by metabolically activated aflatoxin B1.

    Science.gov (United States)

    Foster, P L; Eisenstadt, E; Miller, J H

    1983-05-01

    We have determined the base substitutions generated by metabolically activated aflatoxin B1 in the lacI gene of a uvrB- strain of Escherichia coli. By monitoring over 70 different nonsense mutation sites, we show that activated aflatoxin B1 specifically induced GxC leads to TxA transversions. One possible pathway leading to this base change involves depurination at guanine residues. We consider this mechanism of mutagenesis in the light of our other findings that the carcinogens benzo[a]pyrene diol epoxide and N-acetoxyacetylaminofluorene also specifically induce GxC leads to TxA transversions. PMID:6405385

  8. Brassinolide activities of 2alpha,3alpha-diols versus 3alpha,4alpha-diols in the bean second internode bioassay: Explanation by molecular modeling methods

    Czech Academy of Sciences Publication Activity Database

    Šíša, Miroslav; Vilaplana-Polo, M.; Ballesteros, C. B.; Kohout, Ladislav

    2007-01-01

    Roč. 72, 11/12 (2007), s. 740-750. ISSN 0039-128X R&D Projects: GA AV ČR 1QS510680561; GA MŠk 1M06030 Institutional research plan: CEZ:AV0Z40550506 Keywords : 3D-SAR * 3D-QSAR * biologically active steroids * brassinosteroids Subject RIV: CC - Organic Chemistry Impact factor: 2.143, year: 2007

  9. Brassinolide activities 2alpha, 3alpha - diols versus 3alpha, 4alpha - diols in the bean second internode bioassay: explanation by molecular modeling methods

    Czech Academy of Sciences Publication Activity Database

    Šíša, Miroslav; Vilaplana-Polo, M.; Ballesteros, C. B.; Kohout, Ladislav

    Brno : Mendelova zemědělská a lesnická univerzita v Brně, 2007. s. 7. ISBN 978-80-7375-090-9. [Funkční genomika a proteomika ve šlechtění rostlin. 24.09.2007-25.09.2007, Křtiny] Institutional research plan: CEZ:AV0Z40550506 Keywords : brassinolid * plant stress * molecular modeling Subject RIV: CC - Organic Chemistry

  10. Laterally substituted naphthalene-2,7-diol-based bent-shaped liquid crystals

    Czech Academy of Sciences Publication Activity Database

    Kozmík, V.; Kuchař, M.; Svoboda, J.; Novotná, Vladimíra; Glogarová, Milada; Baumeister, U.; Diele, S.; Pelzl, G.

    2005-01-01

    Roč. 32, č. 9 (2005), s. 1151-1160. ISSN 0267-8292 R&D Projects: GA ČR(CZ) GA202/02/0840; GA ČR(CZ) GA202/05/0431; GA MŠk(CZ) 1P04OCD14.60 Grant ostatní: EU(XE) COST D14 WG 00015 Institutional research plan: CEZ:AV0Z1010914 Keywords : naphthalene - based liquid crystals * x-ray Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 1.432, year: 2005

  11. The waterborne polyurethane dispersions based on polycarbonate diol: effect of ionic content

    Czech Academy of Sciences Publication Activity Database

    Cakić, S. M.; Špírková, Milena; Ristić, I. S.; B-Simendić, J. K.; M-Cincović, M.; Poreba, Rafal

    2013-01-01

    Roč. 138, č. 1 (2013), s. 277-285. ISSN 0254-0584 R&D Projects: GA ČR GAP108/10/0195 Institutional research plan: CEZ:AV0Z40500505 Keywords : coatings * chemical synthesis * thermogravimetric analysis (TGA) Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.129, year: 2013

  12. The investigation of the reactions of some pyrazole-3-carboxylic acids with various diamines and diols

    Directory of Open Access Journals (Sweden)

    Rahmi Kasımoğulları

    2012-06-01

    Full Text Available In this study, some new derivatives were synthesized of 4-benzoyl-1-(3-nitrophenyl-5-phenyl-1H-pyrazole-3-carboxylic acid (1 and 4-(ethoxycarbonyl-1-(3-nitrophenyl-5-phenyl-1H-pyrazole-3-carboxylic acid (2 that they were pyrazole carboxylic acid derivatives. Firstly, 1 and 2 reacted with SOCl2 to transform them into acyl chlorides (3, 4. Then various bis-carboxamide derivatives (5–8 were obtained from the reaction of 3 and 4 with various diamines and also a ;#946;-hydroxy ester (9 derivative was obtained from the reaction of 3 with ethylene glycol. The structures of synthesized compounds were elucidated with using FT-IR, 1H NMR, 13C NMR and elemental analysis methods.

  13. The investigation of the reactions of some pyrazole-3-carboxylic acids with various diamines and diols

    OpenAIRE

    Rahmi Kasımoğulları; Makbule Maden; Samet Mert

    2012-01-01

    In this study, some new derivatives were synthesized of 4-benzoyl-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid (1) and 4-(ethoxycarbonyl)-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid (2) that they were pyrazole carboxylic acid derivatives. Firstly, 1 and 2 reacted with SOCl2 to transform them into acyl chlorides (3, 4). Then various bis-carboxamide derivatives (58) were obtained from the reaction of 3 and 4 with various diamines and also a ;#946;-hydroxy ester (9) deri...

  14. The investigation of the reactions of some pyrazole-3-carboxylic acids with various diamines and diols

    OpenAIRE

    Kasımoğulları, Rahmi; Maden, Makbule; Mert, Samet

    2012-01-01

    In this study, some new derivatives were synthesized of 4-benzoyl-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid (1) and 4-(ethoxycarbonyl)-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid (2) that they were pyrazole carboxylic acid derivatives. Firstly, 1 and 2 reacted with SOCl2 to transform them into acyl chlorides (3, 4). Then various bis-carboxamide derivatives (5–8) were obtained from the reaction of 3 and 4 with various diamines and also a β-hydroxy ester (9)...

  15. A novel fluorescent vesicular sensor for saccharides based on boronic acid-diol interaction.

    Science.gov (United States)

    Zhang, Yujian; He, Zhenfeng; Li, Guowen

    2010-04-15

    A novel amphiphile containing two functional groups of both naphthalene and boronic acid, 2-(hexadecyloxy)-naphthalene-6-boronic acid (HNBA), has been synthesized. Scanning electron microscopy (SEM) indicated the formation of bilayer vesicles in the ethanol/water solution (Phi=0.6). Differential scanning calorimetry (DSC) established the presence of crystal-to-liquid crystal transition at 63.36 degrees C. The vesicular fluorescence properties upon binding with carbohydrates have been studied in ethanol/water buffer at pH 7.4. Addition of saccharides to the vesicular solution, the fluorescent intensities of naphthalene in HNBA vesicles centered at 348 nm decreased dramatically with increasing concentration of saccharides. The change tendency of fluorescent intensities of the HNAB vesicles with concentration of saccharides followed in the order of fructose>galactose>maltose>glucose. The pH profiles of the fluorescence intensity were studied in the absence and in the presence of sugars. Also, the urine sample induced spectral changes of the HNBA vesicles were studied. These results suggest that the HNBA vesicles may be developed as a continuous monitoring and implantable fluorescence vesicular sensor, which might be applied in the practical field. PMID:20188967

  16. Surface characteristics of UV-irradiated polyurethane elastomers extended with α, ω-alkane diols

    International Nuclear Information System (INIS)

    Polyurethane elastomers (PUEs) based on 4,4'-diphenylmethane diisocyanate (MDI), poly (ε-caprolactone) (PCL) and extended with series of chain extender (CE) were synthesized via two step polymerization technique. The synthesized samples were irradiated for 50, 100 and 200 h in an UV exposure unit as such the spectral distribution of the light is good match for terrestrial solar radiation. The modifications in the chemical structures of the PU before and after irradiation were characterized using Fourier transform infrared (FT-IR) technique. The effect of irradiation time and chain extenders length on surface properties were studied and investigated. Photo-oxidation of PU surface leads to fast increase in surface free energy and its polar component. Simultaneously, the work of water adhesion to polymer increases significantly during UV-irradiation. The higher changes in surface properties, observed by water absorption (%), equilibrium degree of swelling, as well as monitored by ATR-FT-IR and contact angle measurement, were found for the PU samples extended with higher number of methylene unit and irradiation time

  17. Chiral selection in the formation of borates from racemic binaphthols and related diols

    OpenAIRE

    Raskatov, Jevgenij A.; Brown, John M.; Amber L. Thompson

    2011-01-01

    A series of racemic or stereochemically labile chiral borate anions based on the 2,2′-biphenol motif was investigated. All borates were homochiral in the solid state, although in some cases the heterochiral diastereomers were computed to be thermodynamically preferred (DFT). The crystallographic preference for the homochiral diastereomer was attributed to its lower bulk, higher molecular symmetry, and the therewith associated better packing ability.

  18. PROPERTIES OF POLYURETHANE ELASTOMERS BASED ON POLY (OXYETHYLENE-co-OXYTETRAMETHYLENE) DIOL

    Institute of Scientific and Technical Information of China (English)

    Chen-yu Su; Guang-li Zhang; Hong-zhi Zhang

    2001-01-01

    Polyurethane elastomers derived from 4,4′-methylene bis(phenyl isocyanate), butylene glycol and the low oxyethylene moiety content copolyether of tetrahydrofuran and ethylene oxide, obtained by copolymerization using heteropolyacid-ethylene oxide initiator system, were prepared. The polyurethanes exhibited an increased water absorption and much better low temperature resilience, which remained high even at a temperature of-3℃, while that of polyurethane based upon poly(tetramethylene ether) glycol of the same molecular weight, I.e. Being 2000, and molecular weight distribution, I.e. In the range of 1.4-1.5, starts to decrease dramatically at 5℃.``

  19. MONOALLYLATION OF DIOLS THROUGH RUTHENIUM-CATALYZED REACTION WITH HOMOALLYL ALCOHOLS. (R822668)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  20. (E-(25S-23-Acetyl-5β-furost-22-ene-3β,26-diol

    Directory of Open Access Journals (Sweden)

    Sylvain Bernès

    2008-03-01

    Full Text Available The title steroid, C29H46O4, is a furostene derivative with a C=C double-bond length of 1.353 (3 Å and an E configuration. The side chain is oriented toward the α face of the A–E steroidal nucleus and presents a disordered terminal CH2—OH group [occupancies for resolved sites are 0.591 (9 and 0.409 (9]. The methyl group at C20 attached to ring E is also oriented toward the α face, avoiding steric hindrance with the carbonyl O atom of the acetyl group. The furostene and acetyl functionalities form an α,β-unsaturated ketone system, with an s-cis configuration. All hydroxy and carbonyl groups are involved in weak intermolecular hydrogen bonds. The absolute configuration was assigned from the synthesis.

  1. Poitediol, a new nonisoprenoid sesquiterpene diol from the marine alga Laurencial poitei

    International Nuclear Information System (INIS)

    The compound was isolated from ethanol extracts of the red seaweed Laurencia poitei(Lamouroux) Howe by extensive liquid chromatography on μ-Porasil. The structure of the compound, established by x-ray crystallography, belongs to the chiral, monoclinic space group P2 with a = 9.412(6), b = 17.489(8), c = 9.721(3)A, and β = 114.69(4)0. A calculated and observed density of 1.09 g/cm3 (Z = 4) indicated that two molecules of C15H26O2 form the asymmetric unit. Poitediol is an unusual sesquiterpene with a trans-fused bicyclo(6.30)undecane. The five-membered ring is in the envelope conformation with C(8) as the flap(0.615A) removed from the plane of atoms C(1), C(11), C(10), and C(9). The eight-membered ring does not assume any simple conformation. Molecular distances and angles are generally in agreement with accepted values. A computer-generated perspective drawing is also included

  2. 1,4-Dibromo­naphthalene-2,3-diol

    OpenAIRE

    Gao, Qinghe; Zhu, Yanping

    2011-01-01

    In the title compound (r.m.s. deviation for the non-H atoms = 0.020 Å), C10H6Br2O2, an intra­molecular O—H⋯O hydrogen bond generates an S(6) ring. In the crystal, the same H atom also forms an inter­molecular O—H⋯O hydrogen bond, generating a C(2) chain propagating in [100]. The other O—H hydrogen forms a weak O—H⋯π inter­action, and short Br⋯Br contacts [3.5972 (9) Å] also occur.

  3. Epoxide compounds. III. Synthesis of amino-β-diols and their PMR spectra

    International Nuclear Information System (INIS)

    The reactions of 2,2,3-trimethyl-5,6-epoxy-3-hexanol with ammonia and primary and secondary amines was studied. A comprehensive NMR spectral analysis was performed and extensive data on spin-spin coupling constants, chemical shift, and line structure are given. Yields and boiling points of the reaction products are tabulated

  4. Access to enantiopure aromatic epoxides and diols using epoxide hzdrolases derived from total biofilter DNA

    Czech Academy of Sciences Publication Activity Database

    Kotík, Michael; Štěpánek, Václav; Grulich, Michal; Kyslík, Pavel; Archelas, A.

    2010-01-01

    Roč. 65, 1-4 (2010), s. 41-48. ISSN 1381-1177 R&D Projects: GA ČR GA204/06/0458 Institutional research plan: CEZ:AV0Z50200510 Keywords : Chiral resolution * Enantioconvergent reaction * Enantioselectivity Subject RIV: CE - Biochemistry Impact factor: 2.330, year: 2010

  5. Modeling airborne benzo(a)pyrene concentrations in the Czech Republic

    Czech Academy of Sciences Publication Activity Database

    Zalel, A.; Yuval, M.; Švecová, Vlasta; Šrám, Radim; Bartoňová, A.; Broday, D. M.

    2015-01-01

    Roč. 101, JAN (2015), s. 166-176. ISSN 1352-2310 Institutional support: RVO:68378041 Keywords : PAHs * B[a]P * Multivariate linear regression * Classification trees * Air pollution monitoring Subject RIV: FP - Other Medical Disciplines Impact factor: 3.281, year: 2014

  6. Entwicklung von Anreicherungs- und Detektionsmethoden umweltrelevanter Analyten (Viren in Trinkwasser;adsorbiertes Benzo[a]pyren)

    OpenAIRE

    Rieger, Martin

    2012-01-01

    Ziel der vorliegenden Arbeit war es, eine Ultrakonzentrierungsanlage zu entwickeln, die einen quantitativen Nachweis von Viren in 30.000-L-Trinkwasserproben ermöglicht. Das entwickelte Anreicherungssystem besteht aus einem drei-stufigen Prozess. Zwei Crossflow-Ultrafiltrations-Anreicherungsschritte sowie eine monolithische Affinitätsfiltration ermöglichen es 30.000 L Trinkwasser innerhalb von 20 h auf ein finales Volumen von 1 mL anzureichern. Dieses Eluat kann direkt in quantitative Nachweis...

  7. Determination of benzo(apyrene content in PM10 using regression methods

    Directory of Open Access Journals (Sweden)

    Jacek Gębicki

    2015-12-01

    Full Text Available The paper presents an attempt of application of multidimensional linear regression to estimation of an empirical model describing the factors influencing on B(aP content in suspended dust PM10 in Olsztyn and Elbląg city regions between 2010 and 2013. During this period annual average concentration of B(aP in PM10 exceeded the admissible level 1.5-3 times. Conducted investigations confirm that the reasons of B(aP concentration increase are low-efficiency individual home heat stations or low-temperature heat sources, which are responsible for so-called low emission during heating period. Dependences between the following quantities were analysed: concentration of PM10 dust in air, air temperature, wind velocity, air humidity. A measure of model fitting to actual B(aP concentration in PM10 was the coefficient of determination of the model. Application of multidimensional linear regression yielded the equations characterized by high values of the coefficient of determination of the model, especially during heating season. This parameter ranged from 0.54 to 0.80 during the analyzed period.

  8. Repair of DNA damage induced by ionizing radiation and benzo[a]pyrene in mammalian cells

    International Nuclear Information System (INIS)

    The biological effects of DNA-damaging agents are codetermined by the structural characteristics of the lesions, the quality and extent of the local distortion of DNA and chromatin structure, and the mode(s) of damage processing used by a given type of cell. Persistent damage (i.e., damage that is not removed before it is reached by DNA replication) may be mostly responsible for mutagenesis and carcinogenesis. To understand the effects of environmental physical and chemical DNA-damaging agents on human health, the mechanisms of damage processing used by human cells have to be elucidated. We report our studies of the excision of gamma-ray products of the 5,6-dihydroxydihydrothymine type (t0/sub 2//sup γ/) in normal human fibroblasts and in fibroblasts from patients with the hereditary diseases Fanconi's anemia (FA) and ataxia telangiectasia (AT). Both diseases are characterized by chromosomal instability and increased susceptibility for the development of cancer. Formation and repair of DNA-benzo[a]pyrene adducts were studied in baby hamster kidney cells, secondary mouse embryo cells, and human lymphoma. The relative persistence of DNA-B[a]P may explain the high mutagenicity of the 7,8-dihydroxy-9,10-epoxy-tetrahydrobenzo[a]pyrene metabolites in rodent cells that has been observed by several investigators

  9. Comparative in vitro metabolism and activation of benzo(a)pyrene from two species of catfish

    Energy Technology Data Exchange (ETDEWEB)

    Ploch, S.A.; Di Giulio, R.T. [Duke Univ., Durham, NC (United States)

    1995-12-31

    Cytochrome P4501A activity as measured by hepatic ethoxyresorufin-O-deethylase EROD in isolated microsomes is consistently found to be 10 to 20 fold higher in channel catfish (Ictalurus punctuatus) than in a closely related species of catfish, the brown bullhead (Ameriurus nebulosus). To measure more directly the ability of these two species to activate a model PAH, microsomes and hepatocytes isolated from naphthoflavone induced channel catfish (CC) and brown bullhead (BB) were incubated with [{sup 3}H]- or [{sup 14}C]benzo(a)pyrene (BP) to compare metabolite formation and binding to DNA and protein. Microsomes from channel catfish produce 4-fold higher levels of BP metabolites (hexane non-extractable) than brown bullhead (253.0, 9.0 vs 58.8, 14.9 pmole/mg, protein/min). Binding of microsome activated BP to salmon sperm DNA demonstrated a similar 5-fold difference between the two species. Using isolated hepatocytes, the two species demonstrated less pronounced, but consistent differences in metabolite formation (29.85, 2.2 vs 20.1, 0.96 pmole/10{sup 6}, cells/min, CC vs BB), DNA binding and total protein binding (13.2, 2.53 vs 10.57, 1.72 pmole BP/mg, protein/min, CC vs BB). Surprisingly, these preliminary data suggest that induced CC liver activate a model PAH carcinogen more quickly and produce higher levels of stable adducts than a cancer prone species (brown bullhead). Other aspects of BP activation, detoxification and genotoxicity in these two species may contribute to species` susceptibility to carcinogenesis.

  10. Toxic Effects of Methylated Benzo[a]pyrenes in Rat Liver Stem-Like Cells

    Czech Academy of Sciences Publication Activity Database

    Trilecová, L.; Krčková, S.; Marvanová, S.; Pěnčíková, K.; Krčmář, P.; Neča, J.; Hulínková, P.; Pálková, L.; Ciganek, M.; Milcová, Alena; Topinka, Jan; Vondráček, Jan; Machala, M.

    2011-01-01

    Roč. 24, č. 6 (2011), s. 866-876. ISSN 0893-228X Grant ostatní: GA ČR(CZ) GA525/08/1590 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50040702 Keywords : Ah receptor * DNA adducts * WB F344 cells Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 3.779, year: 2011

  11. Metabolism of nasally instilled benzo(a)pyrene and dihydrosafrole in dogs and monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Petridou-Fischer, J.; Whaley, S.; Dahl, A.

    1987-05-01

    Cytochrome P-450 monooxygenases are found in the nasal cavities of a variety of species and could play an important role in the metabolism of inhaled airborne xenobiotics. The object of this study was to examine the metabolism of /sup 14/C-benzo(a)pyrene (BaP) and /sup 3/H-dihydrosafrole (DHS) deposited at the ethmoid and maxillary turbinate regions in Beagle dogs and Cynomolgus monkeys. While the animals were anesthetized, either compound was instilled at 10 minute intervals for 2 hours through catheters positioned at each region. Cotton swab samples of mucus from the nasopharynx were collected at 30 minute intervals during instillation. Metabolites in mucus were identified using high pressure liquid chromatography. Results showed that both regions in both species were capable of metabolizing BaP and DHS. BaP metabolites identified in the mucus were dihydrodiols, quinones, phenols, and tetrols. DHS metabolites were 2-methoxy-4-propyl-phenol, 2-methoxy-4-(2-propenyl)benzene, and 3,4-methylenedioxy-1-(1-hydroxypropyl)benzene. Radioactivity was found in urine and feces of animals treated with either compound, and was detected in the blood of animals treated with DHS. No differences were noted for the nasal metabolism between the two species. This study indicated that not only the nasal tissues, but also the alimentary tract, may be exposed to metabolites of inhaled xenobiotics carried by the mucus.

  12. Benzo(a)pyrene inhibits the role of the bioturbator Tubifex tubifex in river sediment biogeochemistry

    OpenAIRE

    Mermillod-Blondin, Florian; Foulquier, Arnaud; Gilbert, Franck; Navel, Simon; Montuelle, Bernard; Bellvert, Floriant; Comte, Gilles; Grossi, Vincent; Fourel, François; Lecuyer, Christophe; Simon, Laurent

    2013-01-01

    The interactions between invertebrates and micro-organisms living in streambed sediments often play key roles in the regulation of nutrient and organic matter fluxes in aquatic ecosystems. However, benthic sedi- ments also constitute a privileged compartment for the accumulation of persistent organic pollutants such as PAHs or PCBs that may affect the diversity, abundance and activity of benthic organisms. The objective of this study was to quantify the impact of sediment contamination with t...

  13. Reduced-glutathione concentrations in Boleophthalmus pectinirostris tissues exposed to benzo(a)pyrene

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The concentrations of reduced-glutathione (GSH) in liver and ovary of Boleophthalmus pectinirostris are quantified. The concentrations of GSH in the ovary are much higher than that of GSH in the liver(nearly 3 times of the liver). The study also investigates the changes of GSH contents in the two organs while the fishes were exposed to benzo(a)pyrene(BaP) at concentrations of 0, 0.05, 0.2 and 0.5mg/L respectively for up to a week. The concentrations of GSH in the liver of BaP-exposed fish increased significantly with dose, whereas the oncentrations of GSH in the ovary decreased significantly compared to controls. The results suggested that both the liver and the ovary are the primary organ in BaP metabolism, and that the changes of GSH levels may represent an adaptive response or toxic effect to BaP exposure.

  14. Differences in detection of DNA adducts in the 32P-postlabelling assay after either 1-butanol extraction or nuclease Pl treatment

    International Nuclear Information System (INIS)

    The use of nuclease P1 treatment and 1-butanol extraction to increase the sensitivity of the 32P-postlabelling assay for DNA adducts have been compared. Although similar results were obtained with the two methods for standard adducts formed with benzo(a)pyrene diol epoxide I, nuclease P1 treatment resulted in a significant reduction in detection of major adducts 1-amino-6-nitropyrene, 1-amino-8-nitropyrene, 2-aminofluorene, 2-naphthylamine and 4-aminobiphenyl modified DNAs, but not following the 32P-postlabelling analysis of 2-acetylaminofluorene modified DNA. These results suggest that at least initially, both modications of the 32P-postlabelling assay should be used for the detection of unknown adducts or for adducts derived from nitro-aromatics and aromatic amines

  15. Modulation of carcinogen bioavailability by immunisation with benzo[a]pyrene-conjugate vaccines.

    Science.gov (United States)

    Grova, Nathalie; Prodhomme, Emmanuel J F; Schellenberger, Mario T; Farinelle, Sophie; Muller, Claude P

    2009-06-24

    Benzo[a]pyrene (B[a]P) conjugate vaccines based on ovalbumin, tetanus toxoid and diphtheria toxoid (DT) as carrier proteins were developed to investigate the effect of specific antibodies on the bioavailability of this ubiquitous carcinogen and its metabolites. After metabolic activation of this prototype carcinogen, B[a]P forms DNA adducts which initiate chemical carcinogenesis. B[a]P-DT conjugate induced the most robust immune response. The antibodies reacted not only with B[a]P but also with the proximate carcinogen 7,8-diol-B[a]P. Antibodies modulated the bioavailability of B[a]P and its metabolic activation in a dose-dependent manner by sequestration in the blood. Our results showed that this immune prophylactic strategy influences the pharmacokinetic of B[a]P and further studies to investigate their effects on chemical carcinogenesis are warranted. PMID:19406187

  16. Differences in detection of DNA adducts in the 32P-postlabelling assay after either 1-butanol extraction or nuclease P1 treatment.

    Science.gov (United States)

    Gallagher, J E; Jackson, M A; George, M H; Lewtas, J; Robertson, I G

    1989-04-01

    The use of nuclease P1 treatment and 1-butanol extraction to increase the sensitivity of the 32P-postlabelling assay for DNA adducts have been compared. Although similar results were obtained with the two methods for standard adducts formed with benzo[a]pyrene diol epoxide I (BPDE-I), nuclease P1 treatment resulted in a significant reduction in detection of major adducts from 1-amino-6-nitropyrene (1-amino-6-NP), 1-amino-8-nitropyrene (1-amino-8-NP), 2-aminofluorene (2-AF), 2-naphthylamine (2-NA) and 4-aminobiphenyl (4-ABP) modified DNAs, but not following the 32P-postlabelling analysis of 2-acetylaminofluorene (2-AAF) modified DNA. These results suggest that, at least initially, both modifications of the 32P-postlabelling assay should be used for the detection of unknown adducts or for adducts derived from nitroaromatics and aromatic amines. PMID:2540901

  17. Dihydrodiol dehydrogenase and polycyclic aromatic hydrocarbon metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Smithgall, T.E.

    1986-01-01

    Carcinogenic activation of polycyclic aromatic hydrocarbons by microsomal monoxygenases proceeds through trans-dihydrodiol metabolites to diol-epoxide ultimate carcinogens. This thesis directly investigated the role of dihydrodiol dehydrogenase, a cytosolic NAD(P)-linked oxidoreductase, in the detoxification of polycyclic aromatic trans-dihydrodiols. A wide variety of non-K-region trans-dihydrodiols were synthesized and shown to be substrates for the homogeneous rat liver dehydrogenase, including several potent proximate carcinogens derived from 7,12-dimethylbenz(a)anthracene, 5-methylchrysene, and benzo(a)pyrene. Since microsomal activation of polycyclic aromatic hydrocarbons is highly stereospecific, the stereochemical course of enzymatic trans-dihydrodiol oxidation was monitored using circular dichroism spectropolarimetry. The major product formed from the dehydrogenase-catalyzed oxidation of the trans-1,2-dihydrodiol of naphthalene was characterized using UV, IR, NMR, and mass spectroscopy, and appears to be 4-hydroxy-1,2-naphthoquinone. Mass spectral analysis suggests that an analogous hydroxylated o-quinone is formed as the major product of benzo(a)pyrene-7,8-dihydrodiol oxidation. Enzymatic oxidation of trans-dihydrodiols was shown to be potently inhibited by all of the major classes of the nonsteroidal antiinflammatory drugs. Enhancement of trans-dihydrodiol proximate carcinogen oxidation may protect against possible adverse effects of the aspirin-like drugs, and help maintain the balance between activation and detoxification of polycyclic aromatic hydrocarbons.

  18. Bis(1,10-phenanthroline-κ2N,N′(sulfato-Ocopper(II ethane-1,2-diol monosolvate

    Directory of Open Access Journals (Sweden)

    Kai-Long Zhong

    2011-09-01

    Full Text Available In the title compound, [Cu(SO4(C12H8N22]·C2H6O2, the CuII ion is five-coordinated in a distorted square-pyramidal manner by four N atoms from two chelating 1,10-phenanthroline (phen ligands and one O atom from a monodentate sulfate anion. The four N atoms comprise a square and the one O atom the apex of a square pyramid. The two chelating N2C2 groups are oriented at 71.1 (2°. In the crystal, the components are connected by intermolecular O—H...O hydrogen bonding. The presence of pseudosymmetry in the structure suggests the higher symmetry space group C2/c, but attempts to refine the structure in this space group resulted in an unsatisfactory model.

  19. High efficient acetalization of carbonyl compounds with diols catalyzed by novel carbon-based solid strong acid catalyst

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The novel carbon-based acid catalyst has been applied to catalyzing the acetalization and ketalization. The results showed that the catalyst was very efficient with the average yield over 93%. The novel heterogeneous catalyst has the advantages of high activity, wide applicability even to 7-membered ring acetals, strikingly simple workup procedure, non-pollution, and reusability, which will contribute to the green process greatly.

  20. The influence of montmorillonite and bentonite addition on thermal properties of polyurethanes based on aliphatic polycarbonate diols

    Czech Academy of Sciences Publication Activity Database

    Pavličević, J.; Špírková, Milena; Strachota, Adam; Meszaros Szecsenyi, K.; Lazić, N.; Budinski-Simendic, J.

    2010-01-01

    Roč. 509, 1/2 (2010), s. 73-80. ISSN 0040-6031 R&D Projects: GA ČR GAP108/10/0195 Institutional research plan: CEZ:AV0Z40500505 Keywords : segmented polyurethanes * thermal stability * elastomers Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.908, year: 2010

  1. Mechanism of formation of 3-chloropropan-1,2-diol (3-MCPD) esters under conditions of the vegetable oil refining.

    Science.gov (United States)

    Šmidrkal, Jan; Tesařová, Markéta; Hrádková, Iveta; Berčíková, Markéta; Adamčíková, Aneta; Filip, Vladimír

    2016-11-15

    3-MCPD esters are contaminants that can form during refining of vegetable oils in the deodorization step. It was experimentally shown that their content in the vegetable oil depends on the acid value of the vegetable oil and the chloride content. 3-MCPD esters form approximately 2-5 times faster from diacylglycerols than from monoacylglycerols. It has been proved that the higher fatty acids content in the oil caused higher 3-MCPD esters content in the deodorization step. Neutralization of free fatty acids in the vegetable oil before the deodorization step by alkaline carbonates or hydrogen carbonates can completely suppress the formation of 3-MCPD esters. Potassium salts are more effective than sodium salts. PMID:27283615

  2. Cyclopentadienyl-based Trioxo-rhenium Complexes for the Catalytic Deoxydehydration of Diols and Bio-based Polyols to Olefins

    OpenAIRE

    RAJU, S

    2015-01-01

    Renewable sources like biomass, which mainly consists of materials derived from trees and plants, are currently considered as a key and future feedstock in the chemical industry for the sustainable production of chemicals. After the pre-treatment of biomass, lignocellulosic biomass is obtained as the major component. This contains various polymeric compounds such as starch, cellulose and lignin. By breaking these polymers into smaller monomeric molecules, sugars, polyols and aromatic compound...

  3. (20S)-Dammar-24-ene-3β,20-diol monohydrate from the bark of Aglaia exima (Meliaceae)

    OpenAIRE

    Agus Safariari; Asep Supriadin; Unang Supratman4); Khalijah Awang; Seik Weng Ng

    2012-01-01

    In the title compound {systematic name: (1R,2R,5R,7R,10R,11R,14S,15R)-14-[(2S)-2-hydroxy-6-methylhept-5-en-2-yl]-2,6,6,10,11-pentamethyltetracyclo[8.7.0.02,7.011,15]heptadecan-5-ol monohydrate}, C30H52O2·H2O, the three fused cyclohexane rings adopt chair conformations and the hydroxy substituent of one of these occupies an axial position. The fused cyclopentane ring adopts an envelope conformation (with the flap atom being the C atom bearing the methyl group) and the 3-methylbut-2-en...

  4. (20S-Dammar-24-ene-3β,20-diol monohydrate from the bark of Aglaia exima (Meliaceae

    Directory of Open Access Journals (Sweden)

    Agus Safariari

    2012-09-01

    Full Text Available In the title compound {systematic name: (1R,2R,5R,7R,10R,11R,14S,15R-14-[(2S-2-hydroxy-6-methylhept-5-en-2-yl]-2,6,6,10,11-pentamethyltetracyclo[8.7.0.02,7.011,15]heptadecan-5-ol monohydrate}, C30H52O2·H2O, the three fused cyclohexane rings adopt chair conformations and the hydroxy substituent of one of these occupies an axial position. The fused cyclopentane ring adopts an envelope conformation (with the flap atom being the C atom bearing the methyl group and the 3-methylbut-2-enyl portion of its substituent is disordered over three sets of sites in a 0.413 (7:0.250 (7:0.337 (7 ratio. The O atoms of both water molecules occupy special positions of 2 site symmetry. In the crystal, Os—H...Ow and Ow—H...Os (s = steroid and w = water hydrogen bonds link hydroxy groups and water molecules, forming a three-dimensional network. The crystal studied was found to be a non-merohedral twin with a 0.518 (1:0.482 (1 component ratio.

  5. Synthesis of 7-ω-Amidoalkyl-substituted 6,7-Dehydroestra-3,17β-diols

    OpenAIRE

    Inohae, Eiko; Thiemann, Thies; Mataka, Shuntaro; Melo'e Silva, M. Cristina; Patricio Catela, Luciana

    1999-01-01

    The entry to the novel C7-alkylsubstituted 6,7-dehydroestrones 10 by addition of C-nucleophiles on the enolate of suitably protected 6-ketoestrone derivative 3, reduction of the 6-keto group in 7, dehydration of 6-hydroxy group in 8 with a subsequent deprotection step is presented. An exemplary transformation of 10 to the 17α-iodoethynylestradiol 12 is shown.

  6. Mechanisms of interaction of radiation with matter

    International Nuclear Information System (INIS)

    This project is concerned with the mechanisms by which polynuclear aromatic (PNA) compounds on the one hand, and ionizing radiation on the other, cause damage to DNA. PNA compounds constitute an important class of environmental pollutants derived from energy-related sources which, upon metabolic activation to diolepoxide derivatives, produce bulky PNA-DNA lesions interfere with the normal DNA replication and transcription processes, and give rise to mutations and the initiation of tumors. Chiral and other stereochemical effects play a key role in determining the biological effects of a given PNA diol epoxide and the potentially mutagenic lesions which are formed. New and efficient methods for synthesizing stereochemically pure and precisely positioned PNA diol epoxide-DNA lesions in small DNA fragments are reported here. We have elucidated the structures of three stereoisomeric benzo[a]pyrene diol epoxide-DNA adducts. How these adducts affect on DNA polymerase fidelity, transcription, and DNA repair are currently being investigated with respect to detailed structure-biological activity correlations. Spectroscopic techniques such as circular dichroism, fluorescence, and photoionization play an important role in the characterizations of the PNA adducts. A new method was developed for measuring the lifetimes as well as the energies of picosecond duration electronically excited states. Using this technique, it is proposed that short-lived (15 ps) charge-transfer (CT) states in the PNA compound tetracene are activated by a 20 ps laser pulse; an unusual external photoemission echo do to the recombination of CT states is observed 85 ps after the pulse

  7. 5-Methylchrysene metabolism in mouse epidermis in vivo, diol epoxide--DNA adduct persistence, and diol epoxide reactivity with DNA as potential factors influencing the predominance of 5-methylchrysene-1,2-diol-3,4-epoxide--DNA adducts in mouse epidermis

    International Nuclear Information System (INIS)

    5-Methylchrysene (5-MeC) can form two bay region dihydrodiol epoxides: 1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (DE-I) which has the methyl group and the epoxide ring in the same bay region, and 7,8-dihydroxy-9,10-epoxy-7,8,10-tetrahydro-5-methylchrysene (DE-II). In a previous study, we observed that the ratio of DE-I:DNA adducts to DE-II:DNA adducts in mouse epidermis, 24 h after application of [3H]5-MeC metabolites was 2.7 to 1. To investigate the basis for this observation we have now studies: (i) the formation of [3H]5-MeC in mouse epidermis in vivo at various time intervals from 0.33 to 24 h; (ii) the persistence of DE-I:DNA adducts and DE-II:DNA adducts in mouse epidermis at 4-48 h after application of [3H]5-MeC; and (iii) the reactions of DE-I and DE-II with calf thymus DNA in vitro. In contrast to results obtained with mouse liver 9000 grams supernatant, the dihydrodiol precursors of DE-I and DE-II were present in equivalent quantities in mouse epidermis in vivo at every time point studied. The ratio of DE-I:DNA adducts to DE-II:DNA adducts in mouse epidermis was constant throughout the time period studied. However, the extent of formation of DE-I:DNA adducts was greater than that of DE-II:DNA adducts upon reaction of DE-I or DE-II with calf thymus DNA in vitro. These results suggest that differences in reactivity with DNA of DE-I and DE-II may bw responsible for the higher levels in mouse epidermis of DE-I:DNA adducts compared with DE-II:DNA adducts and provide a possible basis for the observed enhancing effect of a bay region methyl group on the carcinogenicity of polynuclear aromatic hydrocarbons

  8. Characteristics of copper removal and ion release during copper biosorption by Stenotrophomonas maltophilia in presence of benzo[a]pyrene

    Institute of Scientific and Technical Information of China (English)

    田云; 叶锦韶; 尹华; 彭辉; 李取生; 白洁琼; 谢丹平

    2013-01-01

    The ability of Stenotrophomonas maltophilia was demonstrated to selectively remove Cu2+from Cu(NO3)2 solution under the circumstance that 1 mg/L benzo[a]pyrene(BaP) was either present or not. The removal ratios of 2 and 10 mg/L Cu2+by 0.25 g/L biosorbent are up to 80% and 49% at 10 min, respectively. The biosorption includes ion exchange, NO3 reduction, ion release, and cell oxidation by Cu2+. BaP does not significantly affect Cu2+removal and ion release. Although 2 mg/L Cu2+increases the release of PO4 3, K+, NH4 +and Ca2+, 10 mg/L Cu2+has strong oxidation on cell, and then decreases NO3 reduction and hinders the release of K+, NH4 +and Ca2+. Exogenous cations inhibit the Cu2+biosorption, while additional anions increase the removal ratios of 10 mg/L Cu2+from 52% to 88%.

  9. COMPARATIVE METABOLISM AND EXCRETION OF BENZO(A)PYRENE IN 2 SPECIES OF ICTALURID CATFISH. (R827101)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  10. Pharmacokinetics and oral bioavailability of soil-adsorbed benzo[a]pyrene (BaP) in rats

    International Nuclear Information System (INIS)

    This study was conducted to evaluate the bioavailability and pharmacokinetics of BaP administered orally as the pure chemical or as BaP adsorbed on solid particulates. Sprague-Dawley rats were gavaged with BaP mixed with 14C-BaP in solution (1.0 μmol BaP/kg, 25 μCi/kg) or the equivalent dose adsorbed onto a clay-based soil, a sand-based soil or rodent food. Venous blood samples were collected at predetermined times for 168 hrs and excreta collected at 24-hr intervals. After 168 hrs, animals were euthanized and tissues collected for analysis. Pharmacokinetic evaluation was based upon two-compartment modeling of the blood concentration data. In all groups, greater than 50% of the dose was recovered in the feces within 48 hrs, whereas only 2-5% of the dose was excreted in the urine after 48 hrs. Total recovery in the excreta ranged from 62-80% of the dose. At study termination, BaP was detected only in the liver, kidneys and adrenal glands. For each tissue, the BaP concentration was greatest in the BaP alone group, followed successively by the sand-, food- and clay-adsorbed BaP groups. Within each group, the kidneys and adrenal glands contained the highest and lowest tissue concentration of BaP, respectively. In general, the elimination half-life, time to maximum blood concentration, and rate constants for absorption and distribution were similar between groups. However, the bioavailability of BaP was markedly less in groups administered BaP adsorbed onto a solid matrix (63, 54 and 34% of the BaP alone group in rats administered sand-, food- and clay-adsorbed BaP, respectively). These results demonstrate that adsorption onto various solid matrices decreased the relative bioavailability of BaP, but produced no other marked effect upon the general pharmacokinetic behavior of orally administered BaP

  11. Carcinogenicity of airborne fine particulate benzo(a)pyrene: an appraisal of the evidence and the need for control.

    OpenAIRE

    PERERA, F.

    1981-01-01

    Benzo(a)pyrene(BaP) originating from fossil fuel and other organic combustion processes is largely adsorbed on fine particulate and hence is a widespread atmospheric pollutant. Available emissions and air quality data are based on the total weight of particulate matter without reference to size and give little information on trends and concentrations of fine particulate BaP. Greater reliance on coal, synfuels and diesel fuel for energy production and transportation will significantly increase...

  12. Tumor necrosis factor-alpha potentiates genotoxic effects of benzo[a]pyrene in liver progenitor cells

    Czech Academy of Sciences Publication Activity Database

    Umannová, Lenka; Machala, M.; Kozubík, Alois; Topinka, Jan; Nováková, Zuzana; Milcová, Alena; Vondráček, Jan

    Bratislava, 2007. P1. [Genetic Toxicology and Cancer Prevention. 22.10.2007-24.10.2007, Bratislava] R&D Projects: GA ČR(CZ) GA524/05/0595 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702; CEZ:AV0Z50390512; CEZ:AV0Z50390703 Keywords : tumor necrosis factor-alpha * xenobiotic metabolizing enzymes * PAH Subject RIV: BO - Biophysics

  13. Tumor necrosis factor-alpha potentiates genotoxic effects of benzo[a]pyrene in liver progenitor cells

    Czech Academy of Sciences Publication Activity Database

    Umannová, Lenka; Machala, M.

    Liptovský Ján, 2007. s. 78. ISBN 978-80-969688-5-5. [XXIV. Xenobiochemické sympózium. 22.05.2007-24.05.2007, Liptovský Ján] R&D Projects: GA ČR(CZ) GA524/05/0595 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : environmental pollutant * proinflammatory cytokine * DNA addukt Subject RIV: BO - Biophysics

  14. Effects of environmental carcinogen benzo[a]pyrene in human androgen-dependent prostate adenocarcinoma cell line LNcaP

    Czech Academy of Sciences Publication Activity Database

    Marvanová, S.; Hrubá, E.; Krčmář, P.; Nováková, Zuzana; Milcová, Alena; Topinka, Jan; Souček, Karel; Vondráček, Jan; Machala, M.

    Bratislava, 2007. s. 9-10. [Genetic Toxicology and Cancer Prevention. 22.10.2007-24.10.2007, Bratislava] R&D Projects: GA ČR(CZ) GA310/07/0961 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702; CEZ:AV0Z50390512; CEZ:AV0Z50390703 Keywords : genotoxicity * apoptosis * DNA adducts Subject RIV: BO - Biophysics

  15. CHARACTERIZATION AND QUANTITATION OF BENZO[A]PYRENE DNA ADDUCTS BY SOLID-MATRIX LUMINESCENCE. (R824100)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  16. Phthalic acid and benzo[a]pyrene in soil-plant-water systems amended with contaminated sewage sludge

    DEFF Research Database (Denmark)

    Mougin, C.; Dappozze, F.; Brault, A.;

    2006-01-01

    than 30% after 90 days in the situation of direct soil contamination, amendment with contaminated digested or composted sludge. It is reduced to 10% in the presence of the raw sludge. In that case, the values of phospholipidic fatty acids and dehydrogenase activity are the highest. By contrast, benzo...

  17. Development of basal and induced aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity in the chicken embryo in ovo.

    Science.gov (United States)

    Hamilton, J W; Denison, M S; Bloom, S E

    1983-06-01

    The development of the hepatic microsomal mixed-function oxidase system was studied to determine the basal level of embryonic enzyme activity and the inducibility of this system throughout growth and differentiation. Chicken embryo livers were assayed for basal and inducible hepatic aryl hydrocarbon hydroxylase (AHHase; designated elsewhere as AHH) activity from the first appearance of the liver as a discrete organ at 5 days of incubation (DI) through day 10 after hatching. In addition, whole-embryo and viscera preparations were assayed at 3 and 4 DI. Basal AHHase activity was equal to or greater than adult levels from 3 DI through hatching in all preparations (approximately 0.3-0.5 nmol/min per mg). A 3-fold increase in basal activity above adult values occurred at hatching. The onset of inducibility in chicken embryo liver between 5 and 6 DI was concomitant with hepatocyte differentiation. A developmental profile of 24-hr 3,4,3', 4'-tetrachlorobiphenyl-induced AHHase activity showed 15- to 30-fold induction over controls from 7 DI through day 10 after hatching, with a maximum of 15 nmol/min per mg at 14 DI and day 1 after hatching, a specific activity greater than 50% greater than maximal induction in the adult. Embryonic AHHase activity was also induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3-methylcholanthrene, beta-naphthoflavone, and sodium phenobarbital. Induction kinetics throughout embryonic development were similar to those reported for the adult chicken and other animals. These findings demonstrate development of a mixed-function oxidase system in very early embryogenesis and then in the liver as it differentiates. Liver AHHase activity is inducible throughout development and perinatally but such activity is under strict developmental regulation. The chicken embryo has adult levels of AHHase activity which would be sufficient to achieve metabolic activation of promutagens/carcinogens before and after hepatocyte differentiation. PMID:6407011

  18. Development of basal and induced aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity in the chicken embryo in ovo.

    OpenAIRE

    Hamilton, J. W.; Denison, M. S.; Bloom, S E

    1983-01-01

    The development of the hepatic microsomal mixed-function oxidase system was studied to determine the basal level of embryonic enzyme activity and the inducibility of this system throughout growth and differentiation. Chicken embryo livers were assayed for basal and inducible hepatic aryl hydrocarbon hydroxylase (AHHase; designated elsewhere as AHH) activity from the first appearance of the liver as a discrete organ at 5 days of incubation (DI) through day 10 after hatching. In addition, whole...

  19. VISUALIZATION OF TISSUE DISTRIBUTION AND METABOLISM OF BENZO[A]PYRENE IN EARLY EMBRYONIC MEDAKA (ORYZIAS LATIPES)

    Science.gov (United States)

    Fish early life stages are highly sensitive to exposure to persistent bioaccumulative toxicants (PBTs). The factors that contribute to this are unknown, but may include the distribution of PBTs to sensitive tissues during critical stages of development. Multiphoton laser scannin...

  20. Prostaglandins and their precursors can modify genetic damage-induced by gamma-radiation and benzo(a)pyrene

    International Nuclear Information System (INIS)

    Experiments were performed to study the effect of various prostaglandins (PGs) and their precursors, gamma-linolenic acid (GLA) and arachidonic acid (AA) on gamma-radiation and benzo (a) pyrene (BP)-induced genetic damage to the bone marrow cells of mice, using the sensitive micronucleus (MN) test. Thromboxane B2 prostaglandin E1 and GLA completely prevented BP-induced and reduced to a great degree radiation-induced genetic damage, where as PGE2, PGF2 alpha and AA were without any effect. Since GLA and AA are widely distributed in the cell membranes, and as PGs can be formed virtually in response to any type of stimulus, it is likely that GLA and PGE1 may function as endogenous anti-mutagenic chemicals

  1. 75 FR 39520 - Certain New Chemicals; Receipt and Status Information

    Science.gov (United States)

    2010-07-09

    ... diisocyanate, aliphatic dicarboxylic acid, aliphatic diol, polyether diol, and dihydroxy aliphatic carboxylic... generating derivative systems ] In Table II of this unit, EPA provides the following information (to...

  2. Analysis of 1,2-diol diesters in vernix caseosa by high-performance liquid chromatography - atmospheric pressure chemical ionization mass spectrometry

    Czech Academy of Sciences Publication Activity Database

    Šubčíková, L.; Hoskovec, Michal; Vrkoslav, Vladimír; Čmelíková, T.; Háková, Eva; Míková, Radka; Coufal, P.; Doležal, A.; Plavka, R.; Cvačka, Josef

    2015-01-01

    Roč. 1378, Jan 23 (2015), s. 8-18. ISSN 0021-9673 R&D Projects: GA ČR GAP206/12/0750 Institutional support: RVO:61388963 Keywords : skin lipids * neutral lipids * lipidomics * mass spectrometry * double-bond position Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 4.169, year: 2014

  3. Study on Waterborne Polycarbonate Diols-based Polyurethane%聚碳酸酯型水性聚氨酯的研究

    Institute of Scientific and Technical Information of China (English)

    王全杰; 朱先义; 侯立杰; 蒋艳云; 杜丹华

    2009-01-01

    以聚碳酸酯二醇(PCDL)和4,4'-二苯基甲烷二异氰酸酯(MDI )为主要原料合成水性聚碳酸酯型聚氨酯树脂(PCU).研究了软段分子量、软段用量对PCU力学性能和微观相分离结构的影响.结果表明,随着软段用量的增加,PCU的断裂强度迅速下降,断裂伸长率也有所下降.但相同软段用量,随着分子量的增加,断裂强度非但没有下降,反而有所上升;断裂伸长率略有下降.同时聚碳酸酯二醇可以明显提高聚氨酯的耐黄变性.

  4. Grubbs's Cross Metathesis of Eugenol with cis-2-butene-1, 4-diol to Make a Natural Product: An Organometallic Experiment for the Undergraduate Lab

    Science.gov (United States)

    Taber, Douglass F.; Frankowski, Kevin J.

    2006-01-01

    A modified experimental procedure for the one-step synthesis that is suitable for the undergraduate organic lab is presented. In the course of work towards the more routine use of air-sensitive organometallic complexes such as the Grubb's catalyst, the natural product (E)-4-(4-hydroxy-3-methoxyphenyl) but-2-en-ol, 4, was synthesized.

  5. Hydroformylation of olefins and reductive carbonylation of aryl halides with syngas formed ex situ from dehydrogenative decarbonylation of hexane-1,6-diol

    DEFF Research Database (Denmark)

    Christensen, Stig Holden; Olsen, Esben Paul Krogh; Rosenbaum, Jascha;

    2014-01-01

    A variety of primary alcohols have been investigated as convenient substrates for the ex situ delivery of carbon monoxide and molecular hydrogen in a two-chamber reactor. The gaseous mixture is liberated in one chamber by an iridium-catalysed dehydrogenative decarbonylation of the alcohol and then...

  6. Analysis of 1,2-diol diesters in vernix caseosa by high-performance liquid chromatography with atmospheric pressure chemical ionization mass spectrometry

    Czech Academy of Sciences Publication Activity Database

    Cvačka, Josef; Šubčíková, L.; Vrkoslav, Vladimír; Hoskovec, Michal; Míková, Radka; Čmelíková, T.

    Puerto de la Cruz : Universidad de La Laguna, 2013. s. 258-258. [ITP 2013. International Symposium on Electro- and Liquid Phase- Separation Techniques /20./. 06.10.2013-09.10.2013, Puerto de la Cruz] R&D Projects: GA ČR GAP206/12/0750 Institutional support: RVO:61388963 Keywords : lipids * lipidomics * tandem mass spectrometry Subject RIV: CB - Analytical Chemistry, Separation

  7. Redox-active tetrathiafulvalene and dithiolene compounds derived from allylic 1,4-diol rearrangement products of disubstituted 1,3-dithiole derivatives

    OpenAIRE

    Filipe Vilela; Skabara, Peter J; Mason, Christopher R.; Thomas D. J. Westgate; Asun Luquin; Coles, Simon J.; Hursthouse, Michael B.

    2010-01-01

    We present a series of compounds by exploiting the unusual 1,4-aryl shift observed for electron-rich 1,3-dithiole-2-thione and tetrathiafulvalene (TTF) derivatives in the presence of perchloric acid. The mechanistic features of this rearrangement are discussed since this synthetic strategy provides an alternative route for the synthesis and functionalisation of sulfur rich compounds including redox active compounds of TTFs, and a Ni dithiolene.

  8. Determination of the radioimmunologic concentration of 5-androstene-3β-17β-diole in the blood plasma of patients suffering from common psoriasis

    International Nuclear Information System (INIS)

    A new radioimmunologic method for the determination of ADIOL in the blood plasma was developed. The author produced the antiserum herself and she examined it on cross-reactions. This method resulted to be very sensitive and in the standard curve a linear range of 0.04 ng to 1.5 ng was obtained. Moreover, the ADIOL concentration was determined in the blood plasma of 16 control subjects and of 35 patients suffering from psoriasis. The result was a far-reaching correlation with the results described in literature, although they were obtained by means of differing determination procedures. (orig./MG)

  9. Differential regulation of estrogen receptors α and β by 4-(E)-{(4-hydroxyphenylimino)-methylbenzene, 1,2-diol}, a novel resveratrol analog

    OpenAIRE

    Ronghe, Amruta; Chatterjee, Anwesha; Singh, Bhupendra; Dandawate, Prasad; Murphy, Leigh; Nimee K Bhat; Padhye, Subhash; Bhat, Hari K.

    2014-01-01

    Breast cancer is the second leading cause of death among women in the United States. Estrogens have been implicated as major risk factors in the development of breast neoplasms. Recent epidemiologic studies have suggested a protective role of phytoestrogens in prevention of breast and other cancers. Resveratrol, a naturally occurring phytoestrogen found notably in red grapes, berries and peanuts, has been shown to possess potent anti-cancer properties. However, the poor efficacy of resveratro...

  10. Sarcophine-Diol, a Skin Cancer Chemopreventive Agent, Inhibits Proliferation and Stimulates Apoptosis in Mouse Melanoma B16F10 Cell Line

    OpenAIRE

    Hesham Fahmy; Ahmed, Safwat A.; Szymanski, Pawel T.; Bhimanna Kuppast; Sherief Khalifa

    2011-01-01

    Sarcodiol (SD) is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B16F10 cell line. In this study we report that SD inhibits the de novo DNA synthesis and enh...

  11. Sarcophine-Diol, a Skin Cancer Chemopreventive Agent, Inhibits Proliferation and Stimulates Apoptosis in Mouse Melanoma B16F10 Cell Line

    Directory of Open Access Journals (Sweden)

    Hesham Fahmy

    2011-12-01

    Full Text Available Sarcodiol (SD is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B16F10 cell line. In this study we report that SD inhibits the de novo DNA synthesis and enhances fragmentation of DNA. We also evaluated the antitumor effect of SD on melanoma cell viability using several biomarkers for cell proliferation and apoptosis. SD inhibits the expression levels of signal transducers and activators of transcription protein (STAT-3 and cyclin D1, an activator of cyclin-dependent kinase 4 (Cdk4. SD treatment also enhances cellular level of tumor suppressor protein 53 (p53 and stimulates cleavage of the nuclear poly (ADP-ribose polymerase (cleaved-PARP. SD also enhances cellular levels of cleaved Caspase-3, -8, -9 and stimulates enzymatic activities of Caspase-3, -8 and -9. These results, in addition to inhibition of cell viability, suggest that SD inhibits melanoma cell proliferation by arresting the cell-division cycle in a Go quiescent phase and activates programmed cell death (apoptosis via extrinsic and intrinsic pathways. Finally, these studies demonstrate that SD shows a very promising chemopreventive effect in melanoma B16F10 tumor cells.

  12. Sarcophine-diol, a skin cancer chemopreventive agent, inhibits proliferation and stimulates apoptosis in mouse melanoma B₁₆F₁₀ cell line.

    Science.gov (United States)

    Szymanski, Pawel T; Kuppast, Bhimanna; Ahmed, Safwat A; Khalifa, Sherief; Fahmy, Hesham

    2012-01-01

    Sarcodiol (SD) is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B₁₆F₁₀ cell line. In this study we report that SD inhibits the de novo DNA synthesis and enhances fragmentation of DNA. We also evaluated the antitumor effect of SD on melanoma cell viability using several biomarkers for cell proliferation and apoptosis. SD inhibits the expression levels of signal transducers and activators of transcription protein (STAT-3) and cyclin D1, an activator of cyclin-dependent kinase 4 (Cdk4). SD treatment also enhances cellular level of tumor suppressor protein 53 (p53) and stimulates cleavage of the nuclear poly (ADP-ribose) polymerase (cleaved-PARP). SD also enhances cellular levels of cleaved Caspase-3, -8, -9 and stimulates enzymatic activities of Caspase-3, -8 and -9. These results, in addition to inhibition of cell viability, suggest that SD inhibits melanoma cell proliferation by arresting the cell-division cycle in a Go quiescent phase and activates programmed cell death (apoptosis) via extrinsic and intrinsic pathways. Finally, these studies demonstrate that SD shows a very promising chemopreventive effect in melanoma B₁₆F₁₀ tumor cells. PMID:22363217

  13. Crystal structure of (−-(2R,3S,4R,5R-5-(1,3-dithian-2-yl-3-methyl-1-(triisopropylsilyloxyhexane-2,4-diol

    Directory of Open Access Journals (Sweden)

    Alejandra Cruz-Montanez

    2014-12-01

    Full Text Available The title compound, C20H42O3S2Si, crystallized with two independent molecules (A and B in the asymmetric unit. They consist of syn,anti,anti-stereotetrads with a 1,3-dithiane motif and a primary alcohol protected as the triisopropyl silyl ether. The 1,3-dithiane ring adopts a chair conformation, while the rest of each molecule displays a common zigzag conformation. There is an intramolecular O—H...O hydrogen bond in each molecule. In the crystal, the A and B molecules are linked via O—H...O hydrogen bonds, forming –A–B–A--B-- chains along [010]. The absolute structure was determined by resonant scattering (anomalous scattering [Flack parameter = 0.035 (8].

  14. The complexation of a novel squaric bis(thiosemicarbazone); 3,4-bis{[(aminothioxomethyl)amino]azamethylene}cyclobut-ene-1,2-diol

    Science.gov (United States)

    Seleem, H. S.; Ramadan, A. A. T.; Taha, A.; Eid, M. F.; Samy, F.

    2011-03-01

    A novel chelating agent (Sqtsc; H 4L) bearing both hard and soft donor atoms was synthesized by the condensation of squaric acid with thiosemicarbazide. The ligand has two symmetrical sets of donor atoms (SNO), therefore, it was allowed to react with the metal ions at the mole ratio 2:1 (M:L). Mono- and bi-nuclear chelates were obtained in which the ligand showed a variety of modes of bonding viz. (OO) 2-, (SNNS) 2- and (SNO) 2- per each metal ion supporting the ambidentate and flexidentate characters of the ligand. The mode of bonding and basicity of the ligand depend mainly on the type of the metal cation and its counter anion. All the obtained complexes have the preferable O h-geometry except the VO II-complex ( 7) which has also the preferable square pyramid geometry. Structural elucidation was achieved via elemental and spectral data.

  15. Perfluoroalkylated Derivatives of Diols and Triols. Selectivity in the Reaction of Primary and Secondary Hydroxy Groups with Perfluoroalkylepoxides. Hemocompatibility and Effect on Perfluorocarbon Emulsion

    Czech Academy of Sciences Publication Activity Database

    Církva, Vladimír; Polák, R.; Paleta, O.; Kodíček, K.; Forman, S.

    2002-01-01

    Roč. 67, č. 10 (2002), s. 1436-1448. ISSN 0010-0765 R&D Projects: GA ČR GA203/98/1174; GA MŠk LB98233 Keywords : perfluoroalkyl epoxides * fluoroalkylations * fluorophilic triols Subject RIV: CC - Organic Chemistry Impact factor: 0.848, year: 2002

  16. Structural studies on inclusion compounds and solvent sorption behavior of gradually elongated wheel-and-axle-type diol hosts featuring lateral benzo[b]thiophene units

    Science.gov (United States)

    Katzsch, Felix; Gruber, Tobias; Weber, Edwin

    2016-06-01

    Based on the wheel-and-axle design strategy, a series of six new clathrate hosts featuring two di(benzo[b]thien-2-yl)hydroxymethyl units attached to both ends of a central linear building element of varying length have been synthesized and their capability to form crystalline inclusion compounds with a fixed range of organic solvents are reported. X-ray crystal structures of relevant inclusion compounds have been determined and are comparatively discussed involving structural modification of the host molecules. Organic vapor sorption behavior of the host compounds coated as solid films on the quartz crystal of a QCM device has been studied. Significant differences in the affinities towards solvent vapors dependent both on structural and polarity properties of host and solvent are observed, indicating potential application as mass sensitive materials.

  17. Effect of strand-specific excision repair on the spectra of mutations induced by benzo[a]pyrene-diol epoxide and ultraviolet radiation in diploid human cells

    International Nuclear Information System (INIS)

    To study the effect of excision repair on the spectra of mutations induced in diploid human cells by UV and ±-7β, 8α-dihydroxy-9α,10α-epoxy- 7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE), the author synchronized repair-proficient cells, treated them at the beginning of S phase or in G1 phase several hours prior to the onset of S phase, selected for thioguanine resistant cells, and determined the spectra of mutations in the coding region of the hyproxanthine(guanine)phosphoribosyl-transferase (HPRT) gene in the mutants. As a control, the spectra of mutations similarly induced in repair-deficient xeroderma pigmentosum (XP) cells were compared. There was no difference in the kinds of mutations observed in mutants derived from either cell strain treated with a particular mutagen either in S or in G1. With BPDE, the majority were G.C→T.A transversions; with UV, they were mainly G.C.→A.T transitions. The strand distribution of premutagenic lesions in mutants from repair-proficient cells treated in S or G1 differed significantly. The results strongly support the hypothesis that human cells preferentially repair UV- and BPDE-induced lesions from the transcribed strand of the HPRT gene. To test this, the rate of repair of BPDE adducts from individual strands of the HPRT gene was measured, using the UvrABC exinuclease and Southern hybridizations with strand-specific probes to detect lesions remaining. BPDE lesions were removed from the transcribed strand at a significantly faster rate than from the nontranscribed strand, consistent with my hypothesis. It was found that BPDE adducts were removed faster from either strand of the HPRT gene than from a transcriptionally inactive locus, indicating preferential repair of active genes. The results of these studies provide biochemical and biological evidence of strand-specific DNA repair of BPDE adducts in human cells

  18. A novel AlEt3-promoted tandem reductive rearrangement of 1-benzyloxy-2,3-epoxides: new route to 2-quaternary 1,3-diol units.

    Science.gov (United States)

    Li, De Run; Xia, Wu Jiong; Tu, Yong Qiang; Zhang, Fu Min; Shi, Lei

    2003-03-21

    A novel and highly stereoselective tandem rearrangement-reduction reaction of 1-benzyloxy-2,3-epoxide, under the promotion of triethylaluminum (AlEt3), has been developed to construct a quaternary stereocenter and the hydroxymethyl attached to the carbon center in one-step. PMID:12703829

  19. Crystal structure of (±)-(7RS,8SR)-7-methyl-1,4-dioxa-spiro-[4.5]decane-7,8-diol.

    Science.gov (United States)

    Oishi, Takeshi; Yamamoto, Hiroaki; Sugai, Tomoya; Fukaya, Keisuke; Yamaguchi, Yu; Watanabe, Ami; Sato, Takaaki; Chida, Noritaka

    2015-10-01

    In the title compound, C9H16O4, the five-membered dioxolane ring adopts a twist conformation; two adjacent C atoms deviate alternately from the mean plane of other atoms by -0.297 (4) and 0.288 (4) Å. The spiro-fused cyclo-hexane ring shows a chair form. The hy-droxy group substituted in an axial position makes an intra-molecular O-H⋯O hydrogen bond with one of the O atoms in the cyclic ether, forming an S(6) ring motif. In the crystal, the O-H⋯O hydrogen bond involving the equatorial hy-droxy group connects the mol-ecules into a zigzag chain with a C(5) motif running along the c axis. PMID:26594401

  20. Westphalen's diol diacetate: 19(10→5-abeo-5β-cholest-9-ene-3β,6β-diyl diacetate

    Directory of Open Access Journals (Sweden)

    Johana Ramírez Hernández

    2012-12-01

    Full Text Available The structure of the title steroid [alternative name: 3β,6β-diacetoxy-5β-methyl-19-norcholest-9(10-ene], C31H50O4, confirms the generally accepted mechanism for the rearrangement of a cholestan-5α-ol derivative reported a century ago by Westphalen. The methyl group at position 10 of the starting material migrates to position 5 in the steroidal nucleus, while a Δ9 bond is formed, as indicated by the C=C bond length of 1.347 (4 Å. The methyl transposition leaves the 5R configuration unchanged, with the methyl oriented towards the β face. During the rearrangement, the steroidal B ring experiences a conformational distortion from chair to envelope with the C atom at position 6 as the flap. In the title structure, the isopropyl group of the side chain is disordered over two positions, with occupancies of 0.733 (10 and 0.267 (10. The carbonyl O atom in the acetyl group at C3 is also disordered with an occupancy ratio of 0.62 (4:0.38 (4.

  1. TPX2 in malignantly transformed human bronchial epithelial cells by anti-benzo[a]pyrene-7,8-diol-9,10-epoxide

    International Nuclear Information System (INIS)

    In order to elucidate the function of the targeting protein for Xenopus kinesin-like protein 2 (Xklp2) (TPX2) in the malignant transformation of human bronchial epithelial cells induced by anti-benzo[a]pyrene-trans-7, 8-dihydrodiol-9, 10-epoxide (anti-BPDE), TPX2 was characterized in cells at both the gene and the protein levels. TPX2 was present at higher levels in 16HBE-C cells than in 16HBE cells as demonstrated by two-dimensional gel electrophoresis, immunocytochemistry, Western blot analysis and RT-PCR. TPX2 was also detected in lung squamous-cell carcinoma tissues by immunohistochemistry, but not in normal lung tissues. Depression of TPX2 by RNA interference in 16HBE-C cells led to a decrease in cell proliferation, S-phase cell cycle arrest and cell apoptosis. Abnormal TPX2 tyrosine phosphorylation was detected in 16HBE-C cells, and this could be inhibited, to different degrees, by tyrosine kinase inhibitors. Inhibiting tyrosine phosphorylation in 16HBE-C cells by three selected tyrosine protein kinase inhibitors, tyrphostin 47, AG112 and AG555, caused G0/G1-phase cell cycle arrest. Our results suggest that anti-BPDE can cause the over-expression of TPX2 and its aberrant tyrosine phosphorylation. Misregulation of TPX2 affects the cell cycle state, proliferation rates and apoptosis

  2. Crystal structure of (1S,2R,4S-1-[(morpholin-4-ylmethyl]-4-(prop-1-en-2-ylcyclohexane-1,2-diol

    Directory of Open Access Journals (Sweden)

    Rachid Outouch

    2015-01-01

    Full Text Available The asymmetric unit of the title compound, C14H25NO3, contains two independent molecules with similar geometry. The morpholine and cyclohexane rings of both molecules adopt a chair conformation. Intramolecular O—H...N hydrogen bonds are observed. In the crystal, molecules are linked by O—H...O hydrogen bonds into chains parallel to the [101] direction. The chains are further connected through C—H...O hydrogen bonds forming undulating layers parallel to the (-101 plane. The absolute configuration was assigned by reference to an unchanging chiral centre in the synthetic procedure.

  3. Low-dose synergistic immunosuppression of T-dependent antibody responses by polycyclic aromatic hydrocarbons and arsenic in C57BL/6J murine spleen cells

    International Nuclear Information System (INIS)

    Polycyclic aromatic hydrocarbons (PAHs) and arsenic are both environmental agents that are known to have significant immunotoxicity. Previous studies have shown that PAH exposure of spleen cells in vitro produces significant immune suppression of humoral immunity, especially when P450 activation products are examined. Exposure to arsenic, particularly sodium arsenite, has also been found to be suppressive to antibody responses in vitro and in vivo. The purpose of the present studies was to examine the immunotoxicity of PAHs and arsenite following coexposures with the theory being that the agents may exert synergistic actions, which might be based on their different mechanisms of action. Spleen cells were isolated from male C57BL/6J wild-type mice and treated with PAHs and/or arsenic (arsenite or arsenate). Immunotoxicity assays were used to assess the T-dependent antibody response (TDAR) to sheep red blood cells (SRBCs), measured by a direct plaque-forming cell (PFC) assay. Cell viability was measured by trypan blue staining. Spleen cell viability was not altered following 4 days of PAH and/or arsenic treatment. However, the TDAR demonstrated suppression by both PAHs and arsenic in a concentration-dependent manner. p53 was also induced by NaAsO2 (As3+) and PAHs alone or in combination. The PAHs and their metabolites investigated included benzo[a]pyrene (BaP), BaP-7,8-diol, BaP-7,8-diol-9,10-epoxide (BPDE), 7,12-dimethylbenz[a]anthracene (DMBA), DMBA-3,4-diol, dibenzo[a,l]pyrene (DB[a,l]P). PAH metabolites were found to be more potent than parent compounds in producing immunosuppression and inducing p53 expression. Interestingly, DB[a,l]P, a potent carcinogenic PAH not previously characterized for immunotoxicity, was also found to be strongly immunosuppressive. Arsenite (NaAsO2, As3+) was found to produce immunosuppression at concentrations as low as 0.5 μM and was immunosuppressive at a 10-fold lower concentration than sodium arsenate (Na2HAsO4, As5+). Coexposure

  4. Cigarette side-stream smoke lung and bladder carcinogenesis: inducing mutagenic acrolein-DNA adducts, inhibiting DNA repair and enhancing anchorage-independent-growth cell transformation.

    Science.gov (United States)

    Lee, Hyun-Wook; Wang, Hsiang-Tsui; Weng, Mao-wen; Chin, Chiu; Huang, William; Lepor, Herbert; Wu, Xue-Ru; Rom, William N; Chen, Lung-Chi; Tang, Moon-shong

    2015-10-20

    Second-hand smoke (SHS) is associated with 20-30% of cigarette-smoke related diseases, including cancer. Majority of SHS (>80%) originates from side-stream smoke (SSS). Compared to mainstream smoke, SSS contains more tumorigenic polycyclic aromatic hydrocarbons and acrolein (Acr). We assessed SSS-induced benzo(a)pyrene diol epoxide (BPDE)- and cyclic propano-deoxyguanosine (PdG) adducts in bronchoalveolar lavage (BAL), lung, heart, liver, and bladder-mucosa from mice exposed to SSS for 16 weeks. In SSS exposed mice, Acr-dG adducts were the major type of PdG adducts formed in BAL (p < 0.001), lung (p < 0.05), and bladder mucosa (p < 0.001), with no significant accumulation of Acr-dG adducts in heart or liver. SSS exposure did not enhance BPDE-DNA adduct formation in any of these tissues. SSS exposure reduced nucleotide excision repair (p < 0.01) and base excision repair (p < 0.001) in lung tissue. The levels of DNA repair proteins, XPC and hOGG1, in lung tissues of exposed mice were significantly (p < 0.001 and p < 0.05) lower than the levels in lung tissues of control mice. We found that Acr can transform human bronchial epithelial and urothelial cells in vitro. We propose that induction of mutagenic Acr-DNA adducts, inhibition of DNA repair, and induction of cell transformation are three mechanisms by which SHS induces lung and bladder cancers. PMID:26431382

  5. DNA repair in human bronchial epithelial cells

    International Nuclear Information System (INIS)

    The purpose of this investigation was to compare the response of human cell types (bronchial epithelial cells and fibroblasts and skin fibroblasts) to various DNA damaging agents. Repair of DNA single strand breaks (SSB) induced by 5 krads of X-ray was similar for all cell types; approximately 90% of the DNA SSB were rejoined within one hour. During excision repair of DNA damage from u.v.-radiation, the frequencies of DNA SSB as estimated by the alkaline elution technique, were similar in all cell types. Repair replication as measured by BND cellulose chromatography was also similar in epithelial and fibroblastic cells after u.v.-irradiation. Similar levels of SSB were also observed in epithelial and fibroblastic cells after exposure to chemical carcinogens: 7,12-dimethylbenz[a]anthracene; benzo[a]pyrene diol epoxide (BPDE); or N-methyl-N-nitro-N-nitrosoguanidine. Significant repair replication of BPDE-induced DNA damage was detected in both bronchial epithelial and fibroblastic cells, although the level in fibroblasts was approximately 40% of that in epithelial cells. The pulmonary carcinogen asbestos did not damage DNA. DNA-protein crosslinks induced by formaldehyde were rapidly removed in bronchial cells. Further, epithelial and fibroblastic cells, which were incubated with formaldehyde and the polymerase inhibitor combination of cytosine arabinoside and hydroxyurea, accumulated DNA SSB at approximately equal frequencies. These results should provide a useful background for further investigations of the response of human bronchial cells to various DNA damaging agents

  6. Abnormal expression of c-Myc in human bronchial epithelial cells malignantly transformed by anti-BPDE

    Institute of Scientific and Technical Information of China (English)

    Juan FU; Yiguo JIANG; Xuemin CHEN

    2008-01-01

    Anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (anti-BPDE) is a metabolite of benzo[a]pyrene (B[a] P) and acts as a potent mutagen in mammalian systems. However, molecular mechanisms related to anti-BPDE-induced carcinogenesis are poorly understood. Here, we investigated the expression of proto-oncogene c-myc in human bronchial epithelial cells (16H BE-T) transformed by exposure to anti-BPDE. The levels ofmRNA and pro-tein of c-M yc were examined in the 16HBE-T and vehicle-treated control cells (16HBE-N) by using different meth-ods respectively, including reverse transcriptase-polymer-ase chain reaction (RT-PCR), quantitative real-time PCR (Q-PCR), western blot and immunocytochemical meth-ods. The level of c-myc mRNA appeared to be signifi-cantly increased in 16HBE-T, as compared with those of the 16H BE-N. Likewise, the expression of c-Myc protein was significantly enhanced as compared with those of the control cells. Moreover, the localization of c-Myc protein shows mainly nuclear staining in 16HBE-T. In conclu-sion, the abnormal expression of c-Myc was present in anti-BPDE malignantly transformed 16HBE cells, which may be involved in the carcinogenesis molecular mech-anism of anti-BPDE.

  7. ENDOCRINE DISRUPTIVE ACTIONS OF INHALED BENZO(a)PYRENE ON OVARIAN FUNCTION AND FETAL SURVIVAL IN FISHER F-344 ADULT RATS

    OpenAIRE

    Archibong, Anthony E.; Ramesh, Aramandla; Inyang, Frank; Niaz, Mohammad S.; Hood, Darryl B.; Kopsombut, Prapaporn

    2012-01-01

    This study evaluated the effect of inhaled BaP on female reproductive function. Rats were exposed to 50, or 75 or 100 μg BaP/m3, four hours a day for 14 days via inhalation. Plasma E2, P4, LH and FSH concentrations were determined. Ovarian BaP metabolism and aryl hydrocarbon hydrolase (AHH) activity at proestrus were determined and fertility evaluations were conducted. Ovulation rate and number of pups/litter were reduced in rats exposed to 100 μg BaP/m3 compared with other treatment and cont...

  8. Gene expression profiling in Caco-2 human colon cells exposed to TCDD, benzo[a]pyrene, and natural Ah receptor agonists from cruciferous vegetables and citrus fruits

    NARCIS (Netherlands)

    Waard, de W.J.; Aarts, J.M.M.J.G.; Peijnenburg, A.A.C.M.; Baykus, H.; Talsma, E.F.; Punt, A.; Kok, de T.M.C.M.; Schooten, van F.J.; Hoogenboom, L.A.P.

    2008-01-01

    Cruciferous vegetables and citrus fruits are reported to possess health-beneficial properties, but also have been shown to contain natural aryl hydrocarbon receptor (AhR) agonists (NAhRAs). Binding to the AhR is widely assumed to activate the main pathway by which dioxins, like 2,3,7,8-tetrachlorodi

  9. 苯并(a)芘对热休克因子1的影响%Effects of Benzo(a)pyrene on Heat Shock Factor 1

    Institute of Scientific and Technical Information of China (English)

    杨进波; 徐谦; 蒋长征; 柯磊; 何启强; 白云; 贺涵贞; 胡丙长; 邬堂春

    2004-01-01

    [目的]研究苯并(a)芘(benzo(a)pyrene,BaP)对热休克因子1(heat shookfactor 1,HSF1)的影响.[方法]离体原代培养猪主动脉内皮细胞,以不同浓度的BaP(0、0.1、0.5、1、5、10μmol/L)染毒24 h,分别以Westem-blot法和凝胶阻滞电泳(electrophorefic mobility shift assay,EMSA)法检测各浓度组细胞HSF1表达及HSF1与热休克元件(heat shock element,HSE)结合水平的变化.[结果]低、中浓度(0.1~1 μmol/L)的BaP对HSF1总表达量基本无影响,胞质和胞核HSF1表达量与阴性对照组相比没有明显改变(P>0.05),但随BaP浓度的升高,HSF1有向胞核转移的趋势;而高浓度(5、10μmol/L)的BaP会导致胞浆和胞核HSF1均降低(P<0.05).低、中浓度(0.1~1 μmol/L)BaP作用下,HSF1-HSE结合水平基本不变或略有上升,高浓度(5、10μmol/L)的BaP使HSF1-HSE结合水平明显降低.[结论]BaP作用时,内皮细胞HSF1表达水平与分布、HSF1-HSE结合能力的改变可能是BaP导致热休克蛋白(heat shook protein 70,HSP70)表达降低原因之一;但BaP作用下,内皮细胞HSF1表达水平与分布、HSF1-HSE结合能力的改变与HSP70表达改变并不完全一致,提示研究HSF1与HSE结合之后的改变对进一步揭示BaP致HSP70的基因表达降低的原因有着重要意义.

  10. Tumor necrosis factor-alpha potentiates genotoxic effects of benzo[a]pyrene in rat liver epithelial cells through upregulation of cytochrome P450 1B1 expression

    Czech Academy of Sciences Publication Activity Database

    Umannová, Lenka; Machala, M.; Topinka, Jan; Nováková, Zuzana; Milcová, Alena; Kozubík, Alois; Vondráček, Jan

    2008-01-01

    Roč. 640, 1-2 (2008), s. 162-169. ISSN 0027-5107 R&D Projects: GA ČR(CZ) GA524/05/0595 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702; CEZ:AV0Z50390512; CEZ:AV0Z50390703 Keywords : TNF-alpha * BaP * CYP1B1 Subject RIV: BO - Biophysics Impact factor: 3.198, year: 2008

  11. Influence of immunization with non-genotoxic PAH-KLH conjugates on the resistance of organisms exposed to benzo(a)pyrene

    Czech Academy of Sciences Publication Activity Database

    Černohorská, H.; Klimešová, Š.; Lepša, L.; Jinoch, P.; Milcová, Alena; Schmuczerová, Jana; Topinka, Jan; Lábaj, J.

    2012-01-01

    Roč. 742, 1-2 (2012), s. 2-10. ISSN 1383-5718 R&D Projects: GA MŠk 2B06150 Institutional research plan: CEZ:AV0Z50390703 Keywords : anti-PAH antibodies * DNA adducts * ELISA Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 2.220, year: 2012

  12. Biodegradation of benzo[a]pyrene in soil by Mucor sp. SF06 and Bacillus sp. SB02 co-immobilized on vermiculite

    Institute of Scientific and Technical Information of China (English)

    SU Dan; LI Pei-jun; FRANK Stagnitti; XIONG Xian-zhe

    2006-01-01

    Two indigenous microorganisms, Bacillus sp. SB02 and Mucor sp. SF06, capable of degrading polycyclic aromatic hydrocarbons (PAHs) were co-immobilized on vermiculite by physical adsorption and used to degrade benzo[a] pyrane (BaP). The characteristics of BaP degradation by both free and co-immobilized microorganism were then investigated and compared. The removal rate using the immobilized bacterial-ftmgal mixed consortium was higher than that of the freely mobile mixed consortium. 95.3% of BaP was degraded using the co-immobilized system within 42 d, which was remarkably higher than the removal rate of that by the free strains. The optimal amount of inoculated co-immobilized system for BaP degradation was 2%. The immobilized bacterial-ftmgal mixed consortium also showed better water stability than the free strains. Kinetics of BaP biodegradation by co-immobilized SF06 and SB02 were also studied. The results demonstrated that BaP degradation could be well described by a zero-order reaction rate equation when the initial BaP concentration was in the range of 10-200 mg/kg. The scanning electronic microscope (SEM) analysis showed that the co-immobilized microstructure was suitable for the growth of SF06 and SB02. The mass transmission process of co-immobilized system in soil is discussed. The results demonstrate the potential for employing the bacterial-fungal mixed consortium,co-immobilized on vermiculite, for in situ bioremediation of BaP.

  13. The effect of dietary lipid composition on the intestinal uptake and tissue distribution of benzo[a]pyrene and phenanthrene in Atlantic salmon (Salmo salar).

    Science.gov (United States)

    de Gelder, Stefan; Bakke, Marit J; Vos, Joëlle; Rasinger, Josef D; Ingebrigtsen, Kristian; Grung, Merete; Ruus, Anders; Flik, Gert; Klaren, Peter H M; Berntssen, Marc H G

    2016-01-01

    Uptake of polycyclic aromatic hydrocarbons (PAHs) across the intestine is suggested to occur in association with dietary lipids. Partial replacement of fish ingredients by vegetable ingredients in aquafeeds has led to increased levels of PAHs in marine farmed fish. We therefore investigated, intestinal uptake, tissue distribution and PAH metabolism after a single dose of (14)C-benzo[a]pyrene (BaP) or (14)C-phenanthrene (PHE) given to Atlantic salmon (Salmo salar) acclimatized to a fish oil or vegetable oil based diet. Both BaP and PHE were absorbed along the intestine. Fish oil based feed increased BaP concentration in the pyloric caeca and that of PHE in the proximal intestine. In contrast, vegetable oil increased BaP concentrations in the distal intestine. Extraction of whole body autoradiograms removed PHE-associated radiolabeling almost completely from the intestinal mucosa, but not BaP-associated radiolabeling, indicating the presence of BaP metabolites bound to cellular macromolecules. This observation correlates with the increased cyp1a expression in the proximal intestine, distal intestine and liver in the BaP exposed group. Furthermore, BaP-induced cyp1a expression was higher in the distal intestine of salmon fed fish oil compared to the vegetable oil fed group. PHE had no significant effect on cyp1a expression in any of these tissues. We conclude that dietary lipid composition affects intestinal PAH uptake. Fish oil based feed increased intestinal PAH concentrations probably due to an enhanced solubility in micelles composed of fish oil fatty acids. Increased BaP accumulation in the distal intestine of vegetable oil fed fish seems to be associated with a reduced Cyp1a-mediated BaP metabolism. PMID:26972757

  14. Metabolism of benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene in cultured human bronchus and pancreatic duct

    DEFF Research Database (Denmark)

    1977-01-01

    patients with lung cancer were also compared with those from patients without lung cancer. The profiles were similar except for an observed higher percentage of organic solvent-extractable metabolites formed by bronchi from the noncancer patients that eluted from the column as a single peak. This peak...

  15. Rapid and sensitive determination of benzo[a]pyrene in black ginseng using fluorescence detector and high performance liquid chromatography-tandem mass spectrometry

    Science.gov (United States)

    Cho, Hyun-jeong; Kim, Hye-jin; Son, Byeong-cheol; Jo, Dong-keun; Cho, Byung-lim

    2013-05-01

    Black ginseng is produced by steaming a ginseng root followed by drying repeatedly 9 times during the process and it is changed to be black color, so it is known that a black ginseng has more contents of saponins than red ginseng. However a fake black ginseng which is produced to be black color at high temperature in a short period of time generate carcinogenic benzo[a]pyrene(BaP) through the process. In this year, maximum residue level(MRL) for BaP was established to 2 ug/kg in black ginseng and more sensitive method was developed to quantitatively analyze the BaP by high performance liquid chromatography (HPLC) coupling with florescence detector and tandem mass spectrometry (atmospheric pressure chemical ionization-MS/MS). Chromatographic separation was performed on a Supelcosil™ LC-PAH column (3 μm, 3 mm x 50 mm). Mobile phase A was water and mobile phase B was acetonitrile. BaP was exactly separated from other 15 polycyclic aromatic hydrocarbons (PAHs) which have been selected as priority pollutants by the US Environmental Protection Agency (EPA). Linearity of detection was in the range of 0.2~20 μg/kg and limit of detection (LOD) for BaP was lower than 0.1 μg/kg, limit of quantification (LOQ) was 0.2 μg/kg. The recovery of Bap was 92.54%+/-6.3% in black ginseng.

  16. Proteomic analysis of MCF-7 cells treated with benzo(a)pyrene, dibenzo(a,l)pyrene, coal tar extract, and diesel exhaust extract

    Energy Technology Data Exchange (ETDEWEB)

    Hooven, L.A.; Baird, W.M. [Oregon State University, Corvallis, OR (United States). Dept. for Zoology

    2008-07-15

    Polycyclic aromatic hydrocarbon (PAH) DNA adducts have been associated with carcinogenesis, which is accompanied by multiple alterations in gene expression. We used two-dimensional electrophoresis to distinguish protein expression changes induced in MCF-7 cells by individual PAH (B(a)P and DB(a,l)P) and PAH mixtures (coal tar extract (SRM 1597) and diesel exhaust extract (SRM 1975)). Spots of interest were identified by MALDI-TOF-TOF. Our results have shown alterations in the expression of heat-shock proteins, cytoskeletal proteins, DNA associated proteins, and glycolytic and mitochondrial proteins. The proteins that were universally altered in expression were actin cytoplasmic 1, tubulin alpha and myosin light chain alkali, cyclophilin B, and heterogeneous ribonucleoprotein B1 (a protein involved in access to telomerase and mRNA maturation). Additional proteins with altered expression include histone H{sub 2}A.1, heat-shock protein 70-2, galectin-3, nucleoside diphosphate kinase, ATP synthase, and electron transfer flavoprotein. While sharing similarities, each PAH treatment exhibited a unique proteomic fingerprint.

  17. Oxidative DNA damage following in vivo exposure to Benzo(a)pyrene in the testis, lung and liver of wild type and Ogg1-deficient mice

    OpenAIRE

    2010-01-01

    In the industrial communities of today there is reason for concern for the reproductive health of the male, due to decreasing sperm quality and increased incidences of testicular cancer. Norway and Denmark have the highest incidence rates of testicular cancer in the world. There has traditionally been more focus on the maternal contribution for infertility and defects on the offspring compared to the paternal contribution. The genetic constitution of the offspring depends on the integrity of ...

  18. BENZO(A)PYRENE AND X-RAYS INDUCE REVERSIONS OF THE PINK-EYED UNSTABLE MUTATION IN THE RETINAL PIGMENT EPITHELIUM OF MICE. (R825359)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  19. Inhibition of beta-catenin signalling promotes DNA damage elicited by benzo[a]pyrene in a model of human colon cancer cells via CYP1 deregulation

    Czech Academy of Sciences Publication Activity Database

    Kabátková, Markéta; Zapletal, Ondřej; Tylichová, Zuzana; Neca, J.; Machala, M.; Milcová, Alena; Topinka, Jan; Kozubík, Alois; Vondráček, Jan

    2015-01-01

    Roč. 30, č. 4 (2015), s. 565-576. ISSN 0267-8357 R&D Projects: GA ČR(CZ) GA13-09766S Institutional support: RVO:68081707 ; RVO:68378041 Keywords : ARYL-HYDROCARBON RECEPTOR * POLYCYCLIC AROMATIC-HYDROCARBONS * COLORECTAL- CANCER Subject RIV: BO - Biophysics Impact factor: 2.793, year: 2014

  20. Inflammatory mediators accelerate metabolism of benzo[a]pyrene in rat alveolar type II cells: the role of enhanced cytochrome P450 1B1 expression

    Czech Academy of Sciences Publication Activity Database

    Šmerdová, Lenka; Neča, J.; Svobodová, J.; Topinka, Jan; Schmuczerová, Jana; Kubík, A.; Machala, M.; Vondráček, Jan

    2013-01-01

    Roč. 314, č. 1 (2013), s. 30-38. ISSN 0300-483X R&D Projects: GA ČR GAP503/11/0142 Grant ostatní: GA MZe(CZ) MZE0002716202; GA ČR(CZ) GAP503/11/1227 Institutional research plan: CEZ:AV0Z50040702; CEZ:AV0Z50390703 Institutional support: RVO:68378041 ; RVO:68081707 Keywords : inflammation * CYP1B1 * polycyclic aromatic hydrocarbons Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 3.745, year: 2013