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Sample records for adducts biological effects

  1. Photochemistry of psoralen-DNA adducts, biological effects of psoralen-DNA adducts, applications of psoralen-DNA photochemistry

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Yun-bo

    1988-03-01

    This thesis consists of three main parts and totally eight chapters. In Part I, The author will present studies on the photochemistry of psoralen-DNA adducts, specifically, the wavelength dependencies for the photoreversals of thymidine-HMT (4'-hydroxymethyl-4, 5', 8-trimenthylpsoralen) monoadducts and diadduct and the same adducts incorporated in DNA helices and the wavelength dependecies for the photocrossslinking of thymidine-HMT monoadducts in double-stranded helices. In Part II, The author will report some biological effects of psoralen-DNA adducts, i.e., the effects on double-stranded DNA stability, DNA structure, and transcription by E. coli and T7 RNA polymerases. Finally, The author will focus on the applications of psoralen-DNA photochemistry to investigation of protein-DNA interaction during transcription, which includes the interaction of E. coli and T7 RNA polymerases with DNA in elongation complexes arrested at specific psoralen-DNA adduct sites as revealed by DNase I footprinting experiments. 123 refs., 52 figs., 12 tabs.

  2. ECETOC workshop on the biological significance of DNA adducts: summary of follow-up from an expert panel meeting.

    Science.gov (United States)

    Pottenger, Lynn H; Carmichael, Neil; Banton, Marcy I; Boogaard, Peter J; Kim, James; Kirkland, David; Phillips, Richard D; van Benthem, Jan; Williams, Gary M; Castrovinci, Alexis

    2009-08-01

    This workshop on the biological significance of DNA adducts included presentations of research results in the following areas: endogenous versus exogenous adduct levels; in vitro dose-response data on adducts and mutagenesis from alkylating agents; methyltransferases and alkyl transferase-like proteins in repair of O(6)-alkylguanine adducts; mathematical modeling of threshold dose-response in mutagenesis and carcinogenesis; and the use of genomics to characterize the relationships between adducts, gene expression, and downstream adverse effects. Presentations by regulatory scientists and other authorities addressed the role of adduct and mutation data in risk characterization. Consensus statements were developed and included the following: DNA adducts should be considered as biomarkers of exposure, which may play a key role in establishing a mode of action (MOA) for cancer. Adducts themselves should not be considered as equivalent to mutations or later stage events in carcinogenesis. Although it was not possible at this time to agree on a general level of adducts below which there is no adverse biological effect, there are examples of genotoxic mutagens/carcinogens for which thresholds have been demonstrated. Evidence regarding thresholds for mutations should be considered on a case-by-case basis, in light of available MOA and mechanistic data, to build a knowledge base. Participants agreed that guidance on a recommended format for data presentation (especially agreement on units and appropriate statistical analyses) would be beneficial. Finally, for initial cases, provision of a mechanistic explanation to support a hypothesis of a threshold for mutations was essential for the eventual use of this information in risk assessment.

  3. Chemistry and Biology of Aflatoxin-DNA Adducts

    Energy Technology Data Exchange (ETDEWEB)

    Stone, Michael P.; Banerjee, Surajit; Brown, Kyle L.; Egli, Martin (Vanderbilt)

    2012-03-27

    Aspergillus flavus is a fungal contaminant of stored rice, wheat, corn, and other grainstuffs, and peanuts. This is of concern to human health because it produces the mycotoxin aflatoxin B{sub 1} (AFB{sub 1}), which is genotoxic and is implicated in the etiology of liver cancer. AFB{sub 1} is oxidized in vivo by cytochrome P450 to form aflatoxin B{sub 1} epoxide, which forms an N7-dG adduct (AFB{sub 1}-N7-dG) in DNA. The latter rearranges to a formamidopyrimidine (AFB{sub 1}-FAPY) derivative that equilibrates between {alpha} and {beta} anomers of the deoxyribose. In DNA, both the AFB{sub 1}-N7-dG and AFB{sub 1}-{beta}-FAPY adducts intercalate above the 5'-face of the damaged guanine. Each produces G {yields} T transversions in Escherichia coli, but the AFB{sub 1}-{beta}-FAPY adduct is more mutagenic. The Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) provides a model for understanding error-prone bypass of the AFB{sub 1}-N7-dG and AFB{sub 1}-{beta}-FAPY adducts. It bypasses the AFB{sub 1}-N7-dG adduct, but it conducts error-prone replication past the AFB{sub 1}-FAPY adduct, including mis-insertion of dATP, consistent with the G {yields} T mutations characteristic of AFB{sub 1} mutagenesis in E. coli. Crystallographic analyses of a series of binary and ternary complexes with the Dpo4 polymerase revealed differing orientations of the N7-C8 bond of the AFB{sub 1}-N7-dG adduct as compared to the N{sup 5}-C8 bond in the AFB{sub 1}-{beta}-FAPY adduct, and differential accommodation of the intercalated AFB{sub 1} moieties within the active site. These may modulate AFB{sub 1} lesion bypass by this polymerase.

  4. Pyrrolizidine alkaloid-derived DNA adducts as a common biological biomarker of pyrrolizidine alkaloid-induced tumorigenicity.

    Science.gov (United States)

    Xia, Qingsu; Zhao, Yuewei; Von Tungeln, Linda S; Doerge, Daniel R; Lin, Ge; Cai, Lining; Fu, Peter P

    2013-09-16

    Pyrrolizidine alkaloid-containing plants are the most common poisonous plants affecting livestock, wildlife, and humans. The U.S. National Toxicology Program (NTP) classified riddelliine, a tumorigenic pyrrolizidine alkaloid, as "reasonably anticipated to be a human carcinogen" in the NTP 12th Report on Carcinogens in 2011. We previously determined that four DNA adducts were formed in rats dosed with riddelliine. The structures of the four DNA adducts were elucidated as (i) a pair of epimers of 7-hydroxy-9-(deoxyguanosin-N(2)-yl)dehydrosupinidine adducts (termed as DHP-dG-3 and DHP-dG-4) as the predominant adducts; and (ii) a pair of epimers of 7-hydroxy-9-(deoxyadenosin-N(6)-yl)dehydrosupinidine adducts (termed as DHP-dA-3 and DHP-dA-4 adducts). In this study, we selected a nontumorigenic pyrrolizidine alkaloid, platyphylliine, a pyrrolizidine alkaloid N-oxide, riddelliine N-oxide, and nine tumorigenic pyrrolizidine alkaloids (riddelliine, retrorsine, monocrotaline, lycopsamine, retronecine, lasiocarpine, heliotrine, clivorine, and senkirkine) for study in animals. Seven of the nine tumorigenic pyrrolizidine alkaloids, with the exception of lycopsamine and retronecine, are liver carcinogens. At 8-10 weeks of age, female F344 rats were orally gavaged for 3 consecutive days with 4.5 and 24 μmol/kg body weight test article in 0.5 mL of 10% DMSO in water. Twenty-four hours after the last dose, the rats were sacrificed, livers were removed, and liver DNA was isolated for DNA adduct analysis. DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4 adducts were formed in the liver of rats treated with the individual seven hepatocarcinogenic pyrrolizidine alkaloids and riddelliine N-oxide. These DNA adducts were not formed in the liver of rats administered retronecine, the nontumorigenic pyrrolizidine alkaloid, platyphylliine, or vehicle control. These results indicate that this set of DNA adducts, DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4, is a common biological biomarker of

  5. Environmental air pollution and DNA adducts in Copenhagen bus drivers - effect of GSTM1 and NAT2 genotypes on adduct level

    DEFF Research Database (Denmark)

    Nielsen, Per Sabro; de Pater, Nettie; Okkels, Henrik

    1996-01-01

    The lymphocyte bulky PAH-DNA adduct levels have been studied in persons occupationally exposed to ambient air pollution. The exposure group consisted of 90 healthy, nonsmoking bus drivers from the Copenhagen area, divided into three exposure groups according to driving area, and 60 rural controls...... to levels of exposure to urban air pollution and indicated that these adducts might be helpful as a means of classifying better different exposure groups for epidemiological studies. Furthermore, it demonstrated the ability of 32P-postlabelling to discern small differences in low exposure to ambient air...... pollution and suggested a possible effect of GSTM1*0/0 on DNA adduct levels....

  6. Effect of Laterally Wedged Insoles on the External Knee Adduction Moment across Different Reference Frames.

    Directory of Open Access Journals (Sweden)

    Satoshi Yamaguchi

    Full Text Available Biomechanical effects of laterally wedged insoles are assessed by reduction in the knee adduction moment. However, the degree of reduction may vary depending on the reference frame with which it is calculated. The purpose of this study was to clarify the effect of reference frame on the reduction in the knee adduction moment by laterally wedged insoles.Twenty-nine healthy participants performed gait trials with a laterally wedged insole and with a flat insole as a control. The knee adduction moment, including the first and second peaks and the angular impulse, were calculated using four different reference frames: the femoral frame, tibial frame, laboratory frame and the Joint Coordinate System.There were significant effects of reference frame on the knee adduction moment first and second peaks (P < 0.001 for both variables, while the effect was not significant for the angular impulse (P = 0.84. No significant interaction between the gait condition and reference frame was found in either of the knee adduction moment variables (P = 0.99 for all variables, indicating that the effects of laterally wedged insole on the knee adduction moments were similar across the four reference frames. On the other hand, the average percent changes ranged from 9% to 16% for the first peak, from 16% to 18% for the second peak and from 17% to 21% for the angular impulse when using the different reference frames.The effects of laterally wedged insole on the reduction in the knee adduction moment were similar across the reference frames. On the other hand, Researchers need to recognize that when the percent change was used as the parameter of the efficacy of laterally wedged insole, the choice of reference frame may influence the interpretation of how laterally wedged insoles affect the knee adduction moment.

  7. Effect of external electric field on Cyclodextrin-Alcohol adducts: A DFT study

    Indian Academy of Sciences (India)

    Kundan Baruah; Pradip Kr Bhattacharyya

    2015-06-01

    Effect of external electric fields on the interaction energy between cyclodextrin and alcohol was analyzed in the light of density functional theory (DFT) and density functional reactivity theory (DFRT). Stability of the cyclodextrin-alcohol adducts was measured in terms of DFT based reactivity descriptor, global hardness, electrophilicity, and energy of the HOMO. Stability of adducts was observed to be sensitive towards the strength as well as direction of the applied external electric field. In addition, reactivity pattern follows the maximum hardness and minimum electrophilicity principles.

  8. GSTM1 and XRCC3 Polymorphisms: Effects on Levels of Aflatoxin B1-DNA Adducts

    Institute of Scientific and Technical Information of China (English)

    Xi-dai Long; Yun Ma; Zhou-lin Deng

    2009-01-01

    Objective: Aflatoxin B1 (AFB1), which can cause the formation of AFB1-DNA adducts, is a known human carcinogen. AFB1-exposure individuals with inherited susceptible carcinogen-metabolizing or repairing genotypes may experience an increased risk of genotoxicity. This study was designed to investigate whether the polymorphisms of two genes, the metabolic gene Glutathione S-transferase M1 (GSTM1) and DNA repair gene x-ray repair cross-complementing group 3 (XRCC3), can affect the levels of AFB1-DNA adducts in Guangxi Population (n= 966) from an AFB1-exposure area.Methods: AFB1-DNA adducts were measured by ELISA, and GSTM1 and XRCC3 codon 241 genotypes were identified by PCR-RFLP.Results: The GSTM1-null genotype [adjusted odds ratio (OR) = 2.09; 95% confidence interval (CI) = 1.61(2.71] and XRCC3 genotypes with 241 Met alleles [i.e., XRCC3-TM and -MM, adjusted ORs (95% CI) were 1.43 (1.08(1.89) and 2.42 (1.13(5.22), respectively] were significantly associated with higher levels of AFB1-DNA adducts. Compared with those individuals who did not express any putative risk genotypes as reference (OR = 1), individuals featuring all of the putative risk genotypes did experience a significantly higher DNA-adduct levels (adjusted ORs were 2.87 for GSTM1-null and XRCC3-TM; 5.83 for GSTM1-null and XRCC3-MM). Additionally, there was a positive joint effect between XRCC3 genotypes and long-term AFB1 exposure in the formation of AFB1-DNA adducts.Conclusion: These results suggest that individuals with susceptible genotypes GSTM1-null, XRCC3-TM, or XRCC3-MM may experience an increased risk of DNA damage elicited by AFB1 exposure.

  9. Modulatory effects of essential oils from spices on the formation of DNA adduct by aflatoxin B1 in vitro.

    Science.gov (United States)

    Hashim, S; Aboobaker, V S; Madhubala, R; Bhattacharya, R K; Rao, A R

    1994-01-01

    Essential oils from common spices such as nutmeg, ginger, cardamom, celery, xanthoxylum, black pepper, cumin, and coriander were tested for their ability to suppress the formation of DNA adducts by aflatoxin B1 in vitro in a microsomal enzyme-mediated reaction. All oils were found to inhibit adduct formation very significantly and in a dose-dependent manner. The adduct formation appeared to be modulated through the action on microsomal enzymes, because an effective inhibition on the formation of activated metabolite was observed with each oil. The enzymatic modulation is perhaps due to the chemical constituents of the oils, and this could form a basis for their potential anticarcinogenic roles.

  10. Biological significance of DNA adducts investigated by simultaneous analysis of different endpoints of genotoxicity in L5178Y mouse lymphoma cells treated with methyl methanesulfonate.

    Science.gov (United States)

    Brink, Andreas; Schulz, Berta; Stopper, Helga; Lutz, Werner K

    2007-12-01

    The biological significance of DNA adducts is under continuous discussion because analytical developments allow determination of adducts at ever lower levels. Central questions refer to the biological consequences of adducts and to the relationship between background DNA damage and exposure-related increments. These questions were addressed by measuring the two DNA adducts 7-methylguanine (7-mG) and O(6)-methyl-2'-deoxyguanosine (O(6)-mdGuo) by LC-MS/MS in parallel to two biological endpoints of genotoxicity (comet assay and in vitro micronucleus test), using large batches of L5178Y mouse lymphoma cells treated with methyl methanesulfonate (MMS). The background level of 7-mG was 1440 adducts per 10(9) nucleotides while O(6)-mdGuo was almost 50-fold lower (32 adducts per 10(9) nucleotides). In the comet assay and the micronucleus test, background was in the usual range seen with smaller batches of cells (2.1% Tail DNA and 12 micronuclei-containing cells per 1000 binucleated cells, respectively). For the comparison of the four endpoints for dose-related increments above background in the low-response region we assumed linearity at low dose and used the concept of the "doubling dose", i.e., we estimated the concentration of MMS necessary to double the background measures. Doubling doses of 4.3 and 8.7microM MMS were deduced for 7-mG and O(6)-mdGuo, respectively. For doubling the background measures in the comet assay and the micronucleus test, 5 to 15-fold higher concentrations of MMS were necessary (45 and 66microM, respectively). This means that the contribution of an increase in DNA methylation to biological endpoints of genotoxicity is overestimated. For xenobiotics that generate adducts without background, the difference is even more pronounced because the dose-response curve starts at zero and the limit of detection of an increase is not affected by background variation. Consequences for the question of thresholds in dose-response relationships and for the

  11. Study of the use possibility of the chemical-biological adduct of the 1,1-bis-[5-bromopyrimidine-2’,4’-diono-1’-il]-2-bromo-2’-chloroethylene and bacterial lectin for the treatment of the Pliss’ lymphosarcoma

    Directory of Open Access Journals (Sweden)

    O. V. Welchinska

    2015-04-01

    Full Text Available Aim. Study of the pyrimidine metabolism antimetabolites that can be preformed compounds in the link of biosynthetic processes and can brake tumour’s growth is a more successful, perspective finding direction of new antitumor medications. New original chemical-biological adduct was studied as potential antitumor agent. Methods and results. It was obtained on the base of 1,1-bis-[5-bromopyrimidine-2’,4’-diono-1’-il]-2-bromo-2’-chloroethylene and antitumour bacterial lectin from Bacillus polymyxa. It was found that new chemical-biological adduct of bis-derivative of pyrimidine and bacterial lectin has little toxic preparation (LD50=635 mg/kg and demonstrates considerable antitumour effect upon to 65.5% on Pliss Limphosarcoma tumour. Conclusion. It confirms that new chemical-biological adduct is perspective for the future investigation as substance with a little toxicity and high antitumour activity on the Pliss Limphosarcoma.

  12. Development of a competitive immunoassay for the determination of N-(2-hydroxyethyl)valine adducts in human haemoglobin and its application in biological monitoring.

    Science.gov (United States)

    Ball, Lathan; Jones, Alan; Boogaard, Peter; Will, Wolfgang; Aston, Paul

    2004-01-01

    Ethylene oxide (EO) is an important industrial compound and a directly acting mutagen. Human exposure to it can be monitored by the determination of haemoglobin (Hb) adducts. An immunoassay that quantifies the N-terminal adduct N-(2-hydroxyethyl)valine in whole blood was developed, and its potential usefulness as a tool for biologically monitoring occupational exposure demonstrated. Analytical reliability was confirmed in a comparative study with gas chromatography-mass spectrometry (range 0.040-589 nmol g(-1) Hb, correlation coefficient 0.98, n=10). The assay was configured as a competitive enzyme-linked immunosorbent assay to facilitate the rapid throughput of samples. The assay uses a whole blood matrix and has a working range of 10-10000 pmol N-(2-hydroxyethyl)valine g(-1) hB. The assay does not appear to be affected by structurally similar metabolites and has been used to determine adducts in human blood samples. The first results from potentially exposed workers indicate the assay might be a powerful tool for the routine occupational biomonitoring of EO exposure.

  13. Development of a competitive immunoassay for the determination of N-(2-hydroxypropyl)valine adducts in human haemoglobin and its application in biological monitoring.

    Science.gov (United States)

    Ball, L; Jones, A; Boogaard, P; Will, W; Aston, P

    2005-01-01

    Propylene oxide (PO) is an important industrial compound and a directly acting mutagen. Human exposure to PO can be monitored by the determination of haemoglobin adducts. An immunoassay that quantifies the N-terminal adduct N-(2-hydroxypropyl)valine in whole haemoglobin was developed and its potential usefulness as a tool for biologically monitoring occupational exposure was demonstrated. Analytical reliability was confirmed in a comparative study with GC-MS (range 3.7-992 nmol g-1 haemoglobin (Hb), correlation coefficient 0.99, n=10). The assay has been configured as a competitive enzyme-linked immunosorbent assay to facilitate the rapid throughput of samples. The assay employs a whole blood matrix and has a working range of 2-250 pmol g-1 Hb. It does not appear to be affected by structurally similar metabolites and has been used to determine adducts in human blood samples. The first results in potentially exposed workers indicate the assay's high potential usefulness in routine occupational biomonitoring of exposure to PO.

  14. Foot alignments influence the effect of knee adduction moment with lateral wedge insoles during gait.

    Science.gov (United States)

    Sawada, Tomonori; Tokuda, Kazuki; Tanimoto, Kenji; Iwamoto, Yoshitaka; Ogata, Yuta; Anan, Masaya; Takahashi, Makoto; Kito, Nobuhiro; Shinkoda, Koichi

    2016-09-01

    Lateral wedge insoles (LWIs) reduce the peak external knee adduction moment (KAM). However, the efficacy of LWIs is limited in certain individuals for whom they fail to decrease KAM. Possible explanations for a lack of desired LWI response are variations in foot alignments. The purpose of this study was to evaluate whether the immediate biomechanical effects of LWIs depend on individual foot alignments during gait. Fifteen healthy adults participated in this study. Their feet were categorized as normal, pronated, and supinated using the foot posture index. All subjects were subsequently requested to perform a normal gait under barefoot and LWI conditions. A three-dimensional motion analysis system was used to record the kinematic and kinetic data, included peak KAM, KAM impulse (KAAI), center of pressure displacement, and knee-ground reaction force lever arm (KLA). Furthermore, lower limb frontal plane kinematic parameters at the rear foot, ankle, knee, and hip were evaluated. Among all feet, there was no significant difference in the peak KAM and KAAI between the conditions. In contrast, the peak KAM was significantly reduced under the LWI condition relative to the barefoot condition in the normal foot group. Reductions in the peak KAM were correlated with a more lateral center of pressure and reduced KLA. In addition, a reduced KLA was correlated with decreased hip adduction. LWIs significantly reduced the peak KAM in normal feet, indicating that biomechanical effects of LWIs vary between individual foot alignments. Our findings suggest that it is helpful to assess individual foot alignment to ensure adequate insole treatment for patients with knee osteoarthritis.

  15. Effects of metal ion adduction on the gas-phase conformations of protein ions.

    Science.gov (United States)

    Flick, Tawnya G; Merenbloom, Samuel I; Williams, Evan R

    2013-11-01

    Changes in protein ion conformation as a result of nonspecific adduction of metal ions to the protein during electrospray ionization (ESI) from aqueous solutions were investigated using traveling wave ion mobility spectrometry (TWIMS). For all proteins examined, protein cations (and in most cases anions) with nonspecific metal ion adducts are more compact than the fully protonated (or deprotonated) ions with the same charge state. Compaction of protein cations upon nonspecific metal ion binding is most significant for intermediate charge state ions, and there is a greater reduction in collisional cross section with increasing number of metal ion adducts and increasing ion valency, consistent with an electrostatic interaction between the ions and the protein. Protein cations with the greatest number of adducted metal ions are no more compact than the lowest protonated ions formed from aqueous solutions. These results show that smaller collisional cross sections for metal-attached protein ions are not a good indicator of a specific metal-protein interaction in solution because nonspecific metal ion adduction also results in smaller gaseous protein cation cross sections. In contrast, the collisional cross section of α-lactalbumin, which specifically binds one Ca(2+), is larger for the holo-form compared with the apo-form, in agreement with solution-phase measurements. Because compaction of protein cations occurs when metal ion adduction is nonspecific, elongation of a protein cation may be a more reliable indicator that a specific metal ion-protein interaction occurs in solution.

  16. Formation of an adduct between insulin and the toxic lipoperoxidation product acrolein decreases both the hypoglycemic effect of the hormone in rat and glucose uptake in 3T3 adipocytes.

    Science.gov (United States)

    Medina-Navarro, Rafael; Guzmán-Grenfell, Alberto M; Díaz-Flores, Margarita; Duran-Reyes, Genoveva; Ortega-Camarillo, Clara; Olivares-Corichi, Ivonne M; Hicks, Juan José

    2007-10-01

    Lipid peroxidation induced by reactive oxygen species might modify circulating biomolecules because of the formation of alpha,beta-unsaturated or dicarbonylic aldehydes. In order to investigate the interaction between a lipoperoxidation product, acrolein, and a circulating protein, insulin, the acrolein-insulin adduct was obtained. To characterize the adduct, gel filtration chromatography, sodium dodecylsulfate-polyacrylamide gel electrophoresis and carbonyl determination were performed. Induction of hypoglycemia in the rat and stimulation of glucose uptake by 3T3 adipocytes were used to evaluate the biological efficiency of the adduct compared with that of native insulin (Mackness, B., Quarck, R., Verte, W., Mackness, M., and Holvoet, P. (2006) Arterioscler., Thromb. Vasc. Biol. 26, 1545-1550). Formation of the acrolein-insulin complex in vitro increased the carbonyl group concentration from 2.5 to 22.5 nmol/mg of protein, and it formed without intermolecular aggregates (Halliwell, B., and Whiteman, M. (2004) Br. J. Pharmacol. 142, 231-255. The hypoglycaemic effect 18 min after administration to the rat is decreased by 25% (Robertson, R. P. (2004) J. Biol. Chem. 279, 42351-42354. An adduct concentration of 94 nM, compared to 10 nM for native insulin, was required to obtain the A 50% (concentration needed to obtain 50% of maximum transport of glucose uptake by 3T3 adipocytes). In conclusion, formation of the acrolein-insulin adduct modifies the structure of insulin and decreases its hypoglycemic effect in rat and glucose uptake by 3T3 adipocytes. These results help explain how a toxic aldehyde prone to be produced in vivo can structurally modify insulin and change its biological action.

  17. Acute and sub-acute effects of repetitive kicking on hip adduction torque in injury-free elite youth soccer players

    DEFF Research Database (Denmark)

    Jensen, Jesper; Bandholm, Thomas; Hölmich, Per;

    2014-01-01

    Hip adduction strength is important for kicking and acceleration in soccer players. Changes in hip adduction strength may therefore have an effect on soccer players' athletic performance. The purpose of this study was to investigate the acute and sub-acute effects of a kicking drill session on hip...... strength, concerning isometric hip adduction, abduction and flexion torque of the kicking leg and the supporting leg. Ten injury-free male elite soccer players, mean ± s age of 15.8 ± 0.4 years participated. All players underwent a specific 20 min kicking drill session, comprising 45 kicks. The players...

  18. Hyphenating the curtius rearrangement with Morita-Baylis-Hillman adducts: synthesis of biologically active acyloins and vicinal aminoalcohols

    Energy Technology Data Exchange (ETDEWEB)

    Amarante, Giovanni W.; Cavallaro, Mayra; Coelho, Fernando, E-mail: coelho@iqm.unicamp.b [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Inst. de Quimica. Lab. de Sintese de Produtos Naturais e Farmacos

    2011-07-01

    Using Morita-Baylis-Hillman adducts as substrates, the Curtius rearrangement was performed in a sequence that allowed the synthesis of several hydroxy-ketones (acyloins) with great structural diversity and in good overall yields. These acyloins in turn were easily transformed into 1,2-anti aminoalcohols through a highly diastereoselective reductive amination step. The synthetic utility of these approaches was exemplified by performing the syntheses of (+-)-bupropion, a drug used to treat the abstinence syndrome of smoker and (+-)-spisulosine, a potent anti-tumoral compound originally isolated from a marine source. (author)

  19. Biological effect markers for exposure to carcinogenic compound and their relevance for risk assessment

    NARCIS (Netherlands)

    Delft, J.H.M. van; Baan, R.A.; Roza, L.

    1998-01-01

    In this review data are summarized on biomarkers that are used for biological effect monitoring of human populations exposed to genotoxic carcinogens. The biomarkers are DNA and protein adducts and cytogenetic effects. Most of these biomarkers are relevant for the process of carcinogenesis. Emphasis

  20. Effect of Increased Water Intake on Urinary DNA Adduct Levels and Mutagenicity in Smokers: A Randomized Study

    Directory of Open Access Journals (Sweden)

    Inmaculada Buendia Jimenez

    2015-01-01

    Full Text Available The association between fluid intake and bladder cancer risk remains controversial. Very little is known about to which extent the amount of water intake influences the action of excreting toxics upon the urinary system. This proof of concept trial investigates the effect of water intake on mutagenesis in smokers, a high risk population for bladder cancer. Methods. Monocentric randomized controlled trial. Inclusion Criteria. Male subjects aged 2045–45 y/o, smokers, and small drinkers (24-hour urinary volume 700 mOsmol/kg. Outcomes. 4-ABP DNA adducts formation in exfoliated bladder cells in 24-hour urine collection and urinary mutagenicity in 24-hour urine. Test Group. Subjects consumed 1.5 L daily of the study product (EVIAN on top of their usual water intake for 50 days. Control Group. Subjects continued their usual lifestyle habits. Results. 65 subjects were randomized. Mean age was 30 y/o and mean cigarettes per day were 20. A slight decrease in adducts formation was observed between baseline and last visit but no statistically significant difference was demonstrated between the groups. Urinary mutagenicity significantly decreased. The study shows that increasing water intake decreases urinary mutagenicity. It is not confirmed by urinary adducts formation. Further research would be necessary.

  1. Cisplatin-DNA adduct formation in rat spermatozoa and its effect on fetal development

    NARCIS (Netherlands)

    Hooser, S.T.; Dijk-Knijnenburg, C.M. van; Waalkens-Berendsen, I.D.H.; Smits-van Prooije, A.E.; Snoeij, N.J.; Baan, R.A.; Fichtinger-Schepman, M.J.

    2000-01-01

    Exposure of males to some genotoxic chemicals causes DNA damage in spermatozoa resulting in embryotoxicity and developmental defects in their offspring. This study demonstrates that cisplatin-DNA adducts could be measured in spermatozoa following treatment with the antineoplastic drug, cisplatin. Th

  2. Effects of alkyl chain length and substituent pattern of fullerene bis-adducts on film structures and photovoltaic properties of bulk heterojunction solar cells.

    Science.gov (United States)

    Tao, Ran; Umeyama, Tomokazu; Kurotobi, Kei; Imahori, Hiroshi

    2014-10-08

    A series of alkoxycarbonyl-substituted dihydronaphthyl-based [60]fullerene bis-adduct derivatives (denoted as C2BA, C4BA, and C6BA with the alkyl chain of ethyl, n-butyl, and n-hexyl, respectively) have been synthesized to investigate the effects of alkyl chain length and substituent pattern of fullerene bis-adducts on the film structures and photovoltaic properties of bulk heterojunction polymer solar cells. The shorter alkyl chain length caused lower solubility of the fullerene bis-adducts (C6BA > C4BA > C2BA), thereby resulting in the increased separation difficulty of respective bis-adduct isomers. The device performance based on poly(3-hexylthiophene) (P3HT) and the fullerene bis-adduct regioisomer mixtures was enhanced by shortening the alkyl chain length. When using the regioisomerically separated fullerene bis-adducts, the devices based on trans-2 and a mixture of trans-4 and e of C4BA exhibited the highest power conversion efficiencies of ca. 2.4%, which are considerably higher than those of the C6BA counterparts (ca. 1.4%) and the C4BA regioisomer mixture (1.10%). The film morphologies as well as electron mobilities of the P3HT:bis-adduct blend films were found to affect the photovoltaic properties considerably. These results reveal that the alkyl chain length and substituent pattern of fullerene bis-adducts significantly influence the photovoltaic properties as well as the film structures of bulk heterojunction solar cells.

  3. Quantum Effects in Biology

    Science.gov (United States)

    Mohseni, Masoud; Omar, Yasser; Engel, Gregory S.; Plenio, Martin B.

    2014-08-01

    List of contributors; Preface; Part I. Introduction: 1. Quantum biology: introduction Graham R. Fleming and Gregory D. Scholes; 2. Open quantum system approaches to biological systems Alireza Shabani, Masoud Mohseni, Seogjoo Jang, Akihito Ishizaki, Martin Plenio, Patrick Rebentrost, Alàn Aspuru-Guzik, Jianshu Cao, Seth Lloyd and Robert Silbey; 3. Generalized Förster resonance energy transfer Seogjoo Jang, Hoda Hossein-Nejad and Gregory D. Scholes; 4. Multidimensional electronic spectroscopy Tomáš Mančal; Part II. Quantum Effects in Bacterial Photosynthetic Energy Transfer: 5. Structure, function, and quantum dynamics of pigment protein complexes Ioan Kosztin and Klaus Schulten; 6. Direct observation of quantum coherence Gregory S. Engel; 7. Environment-assisted quantum transport Masoud Mohseni, Alàn Aspuru-Guzik, Patrick Rebentrost, Alireza Shabani, Seth Lloyd, Susana F. Huelga and Martin B. Plenio; Part III. Quantum Effects in Higher Organisms and Applications: 8. Excitation energy transfer in higher plants Elisabet Romero, Vladimir I. Novoderezhkin and Rienk van Grondelle; 9. Electron transfer in proteins Spiros S. Skourtis; 10. A chemical compass for bird navigation Ilia A. Solov'yov, Thorsten Ritz, Klaus Schulten and Peter J. Hore; 11. Quantum biology of retinal Klaus Schulten and Shigehiko Hayashi; 12. Quantum vibrational effects on sense of smell A. M. Stoneham, L. Turin, J. C. Brookes and A. P. Horsfield; 13. A perspective on possible manifestations of entanglement in biological systems Hans J. Briegel and Sandu Popescu; 14. Design and applications of bio-inspired quantum materials Mohan Sarovar, Dörthe M. Eisele and K. Birgitta Whaley; 15. Coherent excitons in carbon nanotubes Leonas Valkunas and Darius Abramavicius; Glossary; References; Index.

  4. Gene-diet interactions in exposure to heterocyclic aromatic amines and bulky DNA adduct levels in blood leukocytes.

    Science.gov (United States)

    Ho, Vikki; Peacock, Sarah; Massey, Thomas E; Godschalk, Roger W L; van Schooten, Frederik J; Chen, Jian; King, Will D

    2015-08-01

    Heterocyclic aromatic amines (HAAs), carcinogens produced in meat when cooked at high temperatures, are an emerging biologic explanation for the meat-colorectal cancer relationship. HAAs form DNA adducts; left unrepaired, adducts can induce mutations, which may initiate/promote carcinogenesis. The purpose of this research was to investigate the relationship between dietary HAAs, genetic susceptibility and bulky DNA adduct levels. Least squares regression was used to examine the relationship between dietary HAA exposure and bulky DNA adduct levels in blood measured using (32)P-postlabeling among 99 healthy volunteers. Gene-diet interactions between dietary HAAs and genetic factors relevant to the biotransformation of HAAs and DNA repair were also examined. No main effects of dietary HAAs on bulky DNA adduct levels was found. However, those with the putative NAT1 rapid acetylator phenotype had lower adduct levels than those with the slow acetylator phenotype (P = 0.02). Furthermore, having five or more 'at-risk' genotypes was associated with higher bulky DNA adduct levels (P = 0.03). Gene-diet interactions were observed between NAT1 polymorphisms and dietary HAAs (P adduct levels compared to lower intakes. This study provides evidence of a biologic relationship between dietary HAAs, genetic susceptibility and bulky DNA adduct formation. However, the lack of a strong main effect of HAAs suggests that dietary HAAs are not a large contributor to bulky DNA adducts in this population; future studies should consider relevant gene-diet interactions to clarify the role of HAAs in carcinogenesis.

  5. The effect of formaldehyde fixation on RNA: optimization of formaldehyde adduct removal.

    Science.gov (United States)

    Evers, David L; Fowler, Carol B; Cunningham, Brady R; Mason, Jeffrey T; O'Leary, Timothy J

    2011-05-01

    Formalin-fixed, paraffin-embedded tissues generally provide low yields of extractable RNA that exhibit both covalent modification of nucleic acid bases and strand cleavage. This frustrates efforts to perform retrospective analyses of gene expression using archival tissue specimens. A variety of conditions have been reported to demodify formaldehyde-fixed RNA in different model systems. We studied the reversal of formaldehyde fixation of RNA using a 50 base RNA oligonucleotide and total cellular RNA. Formaldehyde-adducted, native, and hydrolyzed RNA species were identified by their bioanalyzer electrophoretic migration patterns and RT-quantitative PCR. Demodification conditions included temperature, time, buffer, and pH. The reversal of formaldehyde-fixed RNA to native species without apparent RNA hydrolysis was most successfully performed in dilute Tris, phosphate, or similar buffers (pH 8) at 70°C for 30 minutes. Amines were not required for efficient formaldehyde demodification. Formaldehyde-fixed RNA was more labile than native RNA to treatment with heat and buffer, suggesting that antigen retrieval methods for proteins may impede RNA hybridization or RNA extraction. Taken together, the data indicate that reliable conditions may be used to remove formaldehyde adducts from RNA to improve the quality of RNA available for molecular studies.

  6. Single-stranded oligonucleotide adducts formed by Pt complexes favoring left-handed base canting: steric effect of flanking residues and relevance to DNA adducts formed by Pt anticancer drugs.

    Science.gov (United States)

    Saad, Jamil S; Marzilli, Patricia A; Intini, Francesco P; Natile, Giovanni; Marzilli, Luigi G

    2011-09-01

    Platinum anticancer drug binding to DNA creates large distortions in the cross-link (G*G*) and the adjacent XG* base pair (bp) steps (G* = N7-platinated G). These distortions, which are responsible for anticancer activity, depend on features of the duplex (e.g., base pairing) and of the cross-link moiety (e.g., the position and canting of the G* bases). The duplex structure stabilizes the head-to-head (HH) over the head-to-tail (HT) orientation and right-handed (R) over left-handed (L) canting of the G* bases. To provide fundamental chemical information relevant to the assessment of such duplex effects, we examine (S,R,R,S)-BipPt(oligo) adducts (Bip = 2,2'-bipiperidine with S,R,R,S chiral centers at the N, C, C, and N chelate ring atoms, respectively; oligo = d(G*pG*) with 3'- and/or 5'-substituents). The moderately bulky (S,R,R,S)-Bip ligand favors L canting and slows rotation about the Pt-G* bonds, and the (S,R,R,S)-BipPt(oligo) models provide more useful data than do dynamic models derived from active Pt drugs. All 5'-substituents in (S,R,R,S)-BipPt(oligo) adducts favor the normal HH conformer (∼97%) by destabilizing the HT conformer through clashes with the 3'-G* residue rather than through favorable H-bonding interactions with the carrier ligand in the HH conformer. For all (S,R,R,S)-BipPt(oligo) adducts, the S pucker of the 5'-X residue is retained. For these adducts, a 5'-substituent had only modest effects on the degree of L canting for the (S,R,R,S)-BipPt(oligo) HH conformer. This small flanking 5'-substituent effect on an L-canted HH conformer contrasts with the significant decrease in the degree of R canting previously observed for flanking 5'-substituents in the R-canted (R,S,S,R)-BipPt(oligo) analogues. The present data support our earlier hypothesis that the distortion distinctive to the XG* bp step (S to N pucker change and movement of the X residue) is required for normal stacking and X·X' WC H bonding and to prevent XG* residue clashes.

  7. Effects of the co-carcinogen catechol on benzo(a)pyrene metabolism and DNA adduct formation in mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Melikian, A.A.; Leszczynska, J.M.; Hecht, S.S.; Hoffmann, D.

    1986-01-01

    We have studied the effects of the co-carcinogen catechol (1,2-dihydroxybenzene) on the metabolic activation of (/sup 3/H) benzo(a)pyrene (BaP) in mouse skin, in vivo and on the binding of BaP metabolites to DNA and protein at intervals from 0.5-24 h. Upon topical application of 0.015 mg (/sup 3/H)BaP and 0.25 or 0.5 mg catechol per mouse, catechol had little effect on the total amount of (/sup 3/H)BaP metabolized in mouse skin, but it affected the relative proportions of (/sup 3/H)BaP metabolites. Catechol (0.5 mg/mouse) decreased the proportion of water-soluble (/sup 3/H)BaP metabolites, ethyl acetate-soluble polar metabolites and quinones, but doubled the levels of unconjugated 3-hydroxy-BaP at all measured intervals after treatment. Catechol also caused a small increase in the levels of trans-7,8-dihydroxy-7,8-dihydroBaP and trans-9,10-dihydroxy-9,10-dihydroBaP 0.5 h after treatment. Two hours after treatment, the levels of these metabolites subsided to those of the controls. Catechol did not affect the levels of glutathione conjugates of BaP. However, it caused a decrease in glucuronide and sulphate conjugate formation from BaP. Catechol caused an approximately 2-fold increase in the formation of anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydroBaP (BPDE) DNA adducts and elevated the ratio of anti-syn-BPDE-DNA adducts 1.6 to 2.9-fold. Catechol treatment increased the radioactivity associated with epidermal proteins after (/sup 3/H)BaP application. Because catechol increased levels of 3-hydroxyBaP, we considered the possibility that 3-hydroxyBaP might enhance the tumor initiating activities of BaP or BPDE in mouse skin; a bioassay demonstrated that this was not the case. The results of this study indicate that one important effect of catechol related to its co-carcinogenicity is its ability to enhance formation of anti-BPDE-DNA adducts in mouse skin.

  8. The dramatic effect of the annealing temperature and dielectric functionalization on the electron mobility of indene-C60 bis-adduct thin films.

    Science.gov (United States)

    Orgiu, Emanuele; Squillaci, Marco A; Rekab, Wassima; Börjesson, Karl; Liscio, Fabiola; Zhang, Lei; Samorì, Paolo

    2015-03-28

    Herein we report on the charge transport properties of spin-coated thin films of an n-type fullerene derivative, i.e. the indene-C60 bis-adduct (ICBA). In particular, the effects of annealing temperature and duration as well as surface functionalization are explored. Electron mobilities approaching 0.1 cm(2) V(-1) s(-1) are reported.

  9. Quantitative comparison between in vivo DNA adduct formation from exposure to selected DNA-reactive carcinogens, natural background levels of DNA adduct formation and tumour incidence in rodent bioassays.

    Science.gov (United States)

    Paini, Alicia; Scholz, Gabriele; Marin-Kuan, Maricel; Schilter, Benoît; O'Brien, John; van Bladeren, Peter J; Rietjens, Ivonne M C M

    2011-09-01

    This study aimed at quantitatively comparing the occurrence/formation of DNA adducts with the carcinogenicity induced by a selection of DNA-reactive genotoxic carcinogens. Contrary to previous efforts, we used a very uniform set of data, limited to in vivo rat liver studies in order to investigate whether a correlation can be obtained, using a benchmark dose (BMD) approach. Dose-response data on both carcinogenicity and in vivo DNA adduct formation were available for six compounds, i.e. 2-acetylaminofluorene, aflatoxin B1, methyleugenol, safrole, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and tamoxifen. BMD(10) values for liver carcinogenicity were calculated using the US Environmental Protection Agency BMD software. DNA adduct levels at this dose were extrapolated assuming linearity of the DNA adduct dose response. In addition, the levels of DNA adducts at the BMD(10) were compared to available data on endogenous background DNA damage in the target organ. Although for an individual carcinogen the tumour response increases when adduct levels increase, our results demonstrate that when comparing different carcinogens, no quantitative correlation exists between the level of DNA adduct formation and carcinogenicity. These data confirm that the quantity of DNA adducts formed by a DNA-reactive compound is not a carcinogenicity predictor but that other factors such as type of adduct and mutagenic potential may be equally relevant. Moreover, comparison to background DNA damage supports the notion that the mere occurrence of DNA adducts above or below the level of endogenous DNA damage is neither correlated to development of cancer. These data strongly emphasise the need to apply the mode of action framework to understand the contribution of other biological effect markers playing a role in carcinogenicity.

  10. Effect of center of pressure modulation on knee adduction moment in medial compartment knee osteoarthritis.

    Science.gov (United States)

    Haim, Amir; Wolf, Alon; Rubin, Guy; Genis, Yulya; Khoury, Mona; Rozen, Nimrod

    2011-11-01

    The knee adduction moment (KAM) provides a major contribution to the elevated load in the medial compartment of the knee. An abnormally high KAM has been linked with the progression of knee osteoarthritis (OA). Footwear-generated biomechanical manipulations reduce the magnitude of this moment by conveying a more laterally shifted trajectory of the foot's center of pressure (COP), reducing the distance between the ground reaction force and the center of the knee joint, thus lowering the magnitude of the torque. We sought to examine the outcome of a COP shift in a cohort of female patients suffering from medial knee OA. Twenty-two female patients suffering from medial compartment knee OA underwent successive gait analysis testing and direct pedobarographic examination of the COP trajectory with a foot-worn biomechanical device allowing controlled manipulation of the COP. Modulation of the COP coronal trajectory from medial to lateral offset resulted in a significant reduction of the KAM. This trend was demonstrated in subjects with mild-to-moderate OA and in patients suffering from severe stages of the disease. Our results indicate that controlled manipulation of knee coronal kinetics in individuals suffering from medial knee OA can be facilitated by customized COP modification.

  11. Effect of proprioceptive training on foot posture, lower limb alignment, and knee adduction moment in patients with degenerative knee osteoarthritis: a randomized controlled trial.

    Science.gov (United States)

    Cho, Yumi; Kim, Minkyu; Lee, Wanhee

    2015-02-01

    [Purpose] The purpose of this study was to determine the effect of proprioceptive training on foot progression angle, weight-bearing ratio, and knee adduction moment in patients with degenerative osteoarthritis of the knee. [Subjects] The subjects were 37 patients diagnosed with Kellgren-Lawrence grade 2 or 3 degenerative knee osteoarthritis. They were randomly allocated to three groups: a proprioceptive training group (PT group), quadriceps strengthening group (QS group), and control group. [Methods] The study parameters of the three groups were compared before and after a 12-week training period. Therapeutic exercises were performed twice per week for 12 weeks. Outcomes included the foot progression angle, weight-bearing ratio, and knee adduction moment. [Results] First, a significant difference in the foot progression angle was observed among the groups, significantly increasing in the PTG compared with the CG. Second, a significant difference in the weight-bearing ratio was observed among the groups, significantly increasing in the PTG compared with the CG. Third, a significant difference in the first peak knee adduction moment was observed among the groups, significantly decreasing in the PTG compared with the CG. [Conclusion] The results of the present study indicate that proprioceptive training increased the foot progression angle and weight-bearing ratio and decreased the first peak knee adduction moment. Moreover, incorporating proprioceptive training into a physical therapy exercise program could improve functional ability and delay the progression of degenerative osteoarthritis.

  12. No effects of chlorophyllin on IQ (2-amino-3-methylimidazo[4,5-f]-quinoline)-genotoxicity and -DNA adduct formation in Drosophila.

    Science.gov (United States)

    Negishi, Tomoe; Shinoda, Aki; Ishizaki, Nao; Hayatsu, Hikoya; Sugiyama, Chitose

    2004-02-01

    Previously we demonstrated that chlorophyllin suppressed the genotoxicities of many carcinogens. However, the genotoxicity of IQ (2-amino-3-methylimidazo[4,5-f]quinoline), a carcinogenic heterocyclic amine, was not suppressed in Drosophila. On the contrary, it has been reported that chrolophyllin suppressed the genotoxicity of IQ in rodents, rainbow trout and Salmonella. We demonstrated that the chlorophyllin-induced suppression of MeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline)-genotoxicity was associated with a decrease in MeIQx-DNA adduct formation in Drosophila larval DNA. MeIQx represents another type of heterocyclic amine and is similar to IQ in structure. In this study we utilized (32)P-postlabeling to examine whether chlorophyllin reduced IQ-DNA adduct formation in Drosophila DNA in the same way as MeIQx. The results revealed that the formation of IQ-DNA adducts was unaffected by treatment with chlorophyllin. This was consistent with the absence of any inhibitory effect on genotoxicity as observed in the Drosophila repair test. These results suggest that IQ-behavior in Drosophila is not affected by chlorophyllin, indicating that the process of IQ-DNA adduct formation followed by expression of genotoxicity in Drosophila may be different from that in other organisms.

  13. Chemical-Biological Properties of Zinc Sensors TSQ and Zinquin: Formation of Sensor-Zn-Protein Adducts versus Zn(Sensor)2 Complexes.

    Science.gov (United States)

    Nowakowski, Andrew B; Meeusen, Jeffrey W; Menden, Heather; Tomasiewicz, Henry; Petering, David H

    2015-12-21

    Fluorescent zinc sensors are the most commonly used tool to study the intracellular mobile zinc status within cellular systems. Previously, we have shown that the quinoline-based sensors Zinquin and 6-methoxy-8-p-toluenesulfonamido-quinoline (TSQ) predominantly form ternary adducts with members of the Zn-proteome. Here, the chemistries of these sensors are further characterized, including how Zn(sensor)2 complexes may react in an intracellular environment. We demonstrate that these sensors are typically used in higher concentrations than needed to obtain maximum signal. Exposing cells to either Zn(Zinquin)2 or Zn(TSQ)2 resulted in efficient cellular uptake and the formation of sensor-Zn-protein adducts as evidenced by both a fluorescence spectral shift toward that of ternary adducts and the localization of the fluorescence signal within the proteome after gel filtration of cellular lysates. Likewise, reacting Zn(sensor)2 with the Zn-proteome from LLC-PK1 cells resulted in the formation of sensor-Zn-protein ternary adducts that could be inhibited by first saturating the Zn- proteome with excess sensor. Further, a native SDS-PAGE analysis of the Zn-proteome reacted with either the sensor or the Zn(sensor)2 complex revealed that both reactions result in the formation of a similar set of sensor-Zn-protein fluorescent products. The results of this experiment also demonstrated that TSQ and Zinquin react with different members of the Zn-proteome. Reactions with the model apo-Zn-protein bovine serum albumin showed that both Zn(TSQ)2 and Zn(Zinquin)2 reacted to form ternary adducts with its apo-Zn-binding site. Moreover, incubating Zn(sensor)2 complexes with non-zinc binding proteins failed to elicit a spectral shift in the fluorescence spectrum, supporting the premise that blue-shifted emission spectra are due to sensor-Zn-protein ternary adducts. It was concluded that Zn(sensors)2 species do not play a significant role in the overall reaction between these sensors and

  14. Quantum Effects in Biological Systems

    CERN Document Server

    2016-01-01

    Since the last decade the study of quantum mechanical phenomena in biological systems has become a vibrant field of research. Initially sparked by evidence of quantum effects in energy transport that is instrumental for photosynthesis, quantum biology asks the question of how methods and models from quantum theory can help us to understand fundamental mechanisms in living organisms. This approach entails a paradigm change challenging the related disciplines: The successful framework of quantum theory is taken out of its low-temperature, microscopic regimes and applied to hot and dense macroscopic environments, thereby extending the toolbox of biology and biochemistry at the same time. The Quantum Effects in Biological Systems conference is a platform for researchers from biology, chemistry and physics to present and discuss the latest developments in the field of quantum biology. After meetings in Lisbon (2009), Harvard (2010), Ulm (2011), Berkeley (2012), Vienna (2013), Singapore (2014) and Florence (2015),...

  15. Neuroprotective effect of a new synthetic aspirin-decursinol adduct in experimental animal models of ischemic stroke.

    Directory of Open Access Journals (Sweden)

    Bing Chun Yan

    Full Text Available Stroke is the second leading cause of death. Experimental animal models of cerebral ischemia are widely used for researching mechanisms of ischemic damage and developing new drugs for the prevention and treatment of stroke. The present study aimed to comparatively investigate neuroprotective effects of aspirin (ASA, decursinol (DA and new synthetic aspirin-decursinol adduct (ASA-DA against transient focal and global cerebral ischemic damage. We found that treatment with 20 mg/kg, not 10 mg/kg, ASA-DA protected against ischemia-induced neuronal death after transient focal and global ischemic damage, and its neuroprotective effect was much better than that of ASA or DA alone. In addition, 20 mg/kg ASA-DA treatment reduced the ischemia-induced gliosis and maintained antioxidants levels in the corresponding injury regions. In brief, ASA-DA, a new synthetic drug, dramatically protected neurons from ischemic damage, and neuroprotective effects of ASA-DA may be closely related to the attenuation of ischemia-induced gliosis and maintenance of antioxidants.

  16. Effect of addition of Ag nano powder on mechanical properties of epoxy/polyaminoamide adduct coatings filled with conducting polymer

    Energy Technology Data Exchange (ETDEWEB)

    Samad, Ubair Abdus [Department of Chemical Engineering, College of Engineering, King Saud University, P. O. Box 800, Riyadh 11421 (Saudi Arabia); Center of excellence for research in engineering materials (CEREM), Advance Manufacturing Institute, King Saud University, P. O. Box 800, Riyadh 11421 (Saudi Arabia); Khan, Rawaiz [Department of Chemical Engineering, College of Engineering, King Saud University, P. O. Box 800, Riyadh 11421 (Saudi Arabia); Alam, Mohammad Asif [Center of excellence for research in engineering materials (CEREM), Advance Manufacturing Institute, King Saud University, P. O. Box 800, Riyadh 11421 (Saudi Arabia); Al-Othman, Othman Y. [Department of Chemical Engineering, College of Engineering, King Saud University, P. O. Box 800, Riyadh 11421 (Saudi Arabia); Deanship of Graduate Studies, The Saudi Electric University, P. O. Box 93499, Riyadh 11673 (Saudi Arabia); Al-Zahrani, Saeed M. [Center of excellence for research in engineering materials (CEREM), Advance Manufacturing Institute, King Saud University, P. O. Box 800, Riyadh 11421 (Saudi Arabia); SABIC Polymer Research Center (SPRC) and department of chemical engineering, college of engineering, King Saud University, P. O. Box 800, Riyadh 11421 (Saudi Arabia)

    2015-05-22

    In this study the effect of Ag Nano powder on mechanical properties of epoxy coatings filled with optimized ratio of conducting polymers (Polyaniline and Polyppyrole) was evaluated. Bisphenol A diglycidyl ether epoxy resin (DGEBA) along with polyaminoamide adduct (ARADUR 3282-1 BD) is used as curing agent under optimized stoichiometry values. Curing is performed at room temperature with different percentages of Nano filler. Glass and steel panels were used as coating substrate. Bird applicator was used to coat the samples in order to obtain thin film with wet film thickness (WFT) of about 70-90 µm. The samples were kept in dust free environment for about 7 days at room temperature for complete curing. The coated steel panels were used to evaluate the mechanical properties of coating such as hardness, scratch and impact tests whereas coated glass panels were used for measuring pendulum hardness of the coatings. To check the dispersion and morphology of Nano filler in epoxy matrix scanning electron microscopy (SEM) was used in addition Nano indentation was also performed to observe the effect of Nano filler on modulus of elasticity and hardness at Nano scale.

  17. Effect of addition of Ag nano powder on mechanical properties of epoxy/polyaminoamide adduct coatings filled with conducting polymer

    Science.gov (United States)

    Samad, Ubair Abdus; Khan, Rawaiz; Alam, Mohammad Asif; Al-Othman, Othman Y.; Al-Zahrani, Saeed M.

    2015-05-01

    In this study the effect of Ag Nano powder on mechanical properties of epoxy coatings filled with optimized ratio of conducting polymers (Polyaniline and Polyppyrole) was evaluated. Bisphenol A diglycidyl ether epoxy resin (DGEBA) along with polyaminoamide adduct (ARADUR 3282-1 BD) is used as curing agent under optimized stoichiometry values. Curing is performed at room temperature with different percentages of Nano filler. Glass and steel panels were used as coating substrate. Bird applicator was used to coat the samples in order to obtain thin film with wet film thickness (WFT) of about 70-90 µm. The samples were kept in dust free environment for about 7 days at room temperature for complete curing. The coated steel panels were used to evaluate the mechanical properties of coating such as hardness, scratch and impact tests whereas coated glass panels were used for measuring pendulum hardness of the coatings. To check the dispersion and morphology of Nano filler in epoxy matrix scanning electron microscopy (SEM) was used in addition Nano indentation was also performed to observe the effect of Nano filler on modulus of elasticity and hardness at Nano scale.

  18. Biological Effectiveness of Antiproton Annihilation

    DEFF Research Database (Denmark)

    Maggiore, C.; Agazaryan, N.; Bassler, N.;

    2004-01-01

    from the annihilation of antiprotons produce an increase in ‘‘biological dose’’ in the vicinity of the narrow Bragg peak for antiprotons compared to protons. This experiment is the first direct measurement of the biological effects of antiproton annihilation. The background, description, and status...

  19. Biological Effects of Acoustic Cavitation

    Science.gov (United States)

    2007-11-02

    rectified diffusion. 56 III. STABLE CAVITATION A. Introduction There are manv areas associated with the biological effects of ultrasound in which the...used said as cavitation indicators. Further, if clinical ultrasound systems are found to be inducing cavitation , either stable or transient, it will...O BIOLOGICAL EFFECTS OF ACOUSTIC CAVITATION by Lawrence A. Crum -- Physical Acoustics Research Laboratory Department of Physics and Astronomy ’ CTE

  20. The biologically effective dose in inhalation nanotoxicology.

    Science.gov (United States)

    Donaldson, Ken; Schinwald, Anja; Murphy, Fiona; Cho, Wan-Seob; Duffin, Rodger; Tran, Lang; Poland, Craig

    2013-03-19

    In all branches of toxicology, the biologically effective dose (BED) is the fraction of the total dose of a toxin that actually drives any toxic effect. Knowledge of the BED has a number of applications including in building structure-activity relationships, the selection of metrics, the design of safe particles, and the determination of when a nanoparticle (NP) can be considered to be "new" for regulatory purposes. In particle toxicology, we define the BED as "the entity within any dose of particles in tissue that drives a critical pathophysiogically relevant form of toxicity (e.g., oxidative stress, inflammation, genotoxicity, or proliferation) or a process that leads to it." In conventional chemical toxicology, researchers generally use the mass as the metric to describe dose (such as mass per unit tissue or cells in culture) because of its convenience. Concentration, calculated from mass, may also figure in any description of dose. In the case of a nanoparticle dose, researchers use either the mass or the surface area. The mass of nanoparticles is not the only driver of their activity: the surfaces of insoluble particles interact with biological systems, and soluble nanoparticles can release factors that interact with these systems. Nanoparticle shape can modify activity. In this Account, we describe the current knowledge of the BED as it pertains to different NP types. Soluble toxins released by NPs represent one potential indicator of BED for wholly or partially soluble NPs composed of copper or zinc. Rapid dissolution of these NPs into their toxic ions in the acidic environment of the macrophage phagolysosome causes those ions to accumulate, which leads to lysosome destabilization and inflammation. In contrast, soluble NPs that release low toxicity ions, such as magnesium oxide NPs, are not inflammogenic. For insoluble NPs, ζ potential can serve as a BED measurement because the exposure of the particle surface to the acidic milieu of the phagolysosome and

  1. DNA adducts and strand breaks in workers exposed to vapours and aerosols of bitumen: associations between exposure and effect.

    Science.gov (United States)

    Marczynski, Boleslaw; Raulf-Heimsoth, Monika; Spickenheuer, Anne; Pesch, Beate; Kendzia, Benjamin; Mensing, Thomas; Engelhardt, Beate; Lee, Eun-Hyun; Schindler, Birgit K; Heinze, Evelyn; Welge, Peter; Bramer, Rainer; Angerer, Jürgen; Breuer, Dietmar; Käfferlein, Heiko U; Brüning, Thomas

    2011-06-01

    To study the associations between exposure to vapours and aerosols of bitumen and genotoxic effects, a cross-sectional and cross-shift study was conducted in 320 exposed workers and 118 non-exposed construction workers. Ambient air measurements were carried out to assess external exposure to vapours and aerosols of bitumen. Hydroxylated metabolites of naphthalene, phenanthrene and pyrene were measured in urine, whereas (+)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide ((+)-anti-BPDE), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxodGuo) and DNA strand breaks were determined in blood. Significantly higher levels of 8-oxodGuo adducts and DNA strand breaks were found in both pre- and post-shift blood samples of exposed workers compared to those of the referents. No differences between exposed workers and referents were observed for (+)-anti-BPDE. Moreover, no positive associations between DNA damage and magnitude of airborne exposure to vapours and aerosols of bitumen could be observed in our study. Additionally, no relevant association between the urinary metabolites of PAH and the DNA damage in blood was observed. Overall, our results indicate increased oxidative DNA damage in workers exposed to vapours and aerosols of bitumen compared to non-exposed referents at the group level. However, increased DNA strand breaks in bitumen workers were still within the range of those found in non-exposed and healthy persons as reported earlier. Due to the lack of an association between oxidative DNA damage and exposure levels at the workplaces under study, the observed increase in genotoxic effects in bitumen workers cannot be attributed to vapours and aerosols of bitumen.

  2. Red wine consumption is inversely associated with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-DNA adduct levels in prostate.

    Science.gov (United States)

    Rybicki, Benjamin A; Neslund-Dudas, Christine; Bock, Cathryn H; Nock, Nora L; Rundle, Andrew; Jankowski, Michelle; Levin, Albert M; Beebe-Dimmer, Jennifer; Savera, Adnan T; Takahashi, Satoru; Shirai, Tomoyuki; Tang, Deliang

    2011-10-01

    In humans, genetic variation and dietary factors may alter the biological effects of exposure to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), one of the major heterocyclic amines generated from cooking meats at high temperatures that has carcinogenic potential through the formation of DNA adducts. Previously, we reported grilled red meat consumption associated with PhIP-DNA adduct levels in human prostate. In this study, we expanded our investigation to estimate the associations between beverage consumption and PhIP-DNA adduct levels in prostate for 391 prostate cancer cases. Of the 15 beverages analyzed, red wine consumption had the strongest association with PhIP-DNA adduct levels showing an inverse correlation in both tumor (P = 0.006) and nontumor (P = 0.002) prostate cells. Red wine consumption was significantly lower in African American compared with white cases, but PhIP-DNA adduct levels in prostate did not vary by race. In African Americans compared with whites, however, associations between red wine consumption and PhIP-DNA adduct levels were not as strong as associations with specific (e.g., SULT1A1 and UGT1A10 genotypes) and nonspecific (e.g., African ancestry) genetic variation. In a multivariable model, the covariate for red wine consumption explained a comparable percentage (13%-16%) of the variation in PhIP-DNA adduct levels in prostate across the two racial groups, but the aforementioned genetic factors explained 33% of the PhIP-DNA adduct variation in African American cases, whereas only 19% of the PhIP-DNA adduct variation in whites. We conclude that red wine consumption may counteract biological effects of PhIP exposure in human prostate, but genetic factors may play an even larger role, particularly in African Americans.

  3. Biological effects of electromagnetic fields.

    Science.gov (United States)

    Macrì, M. A.; Di Luzio, Sr.; Di Luzio, S.

    2002-01-01

    Nowadays, concerns about hazards from electromagnetic fields represent an alarming source for human lives in technologically developed countries. We are surrounded by electromagnetic fields everywhere we spend our working hours, rest or recreational activities. The aim of this review is to summarize the biological effects due to these fields arising from power and transmission lines, electrical cable splices, electronic devices inside our homes and work-places, distribution networks and associated devices such as cellular telephones and wireless communication tower, etc. Special care has been reserved to study the biological effects of electromagnetic fields on cell lines of the mammalian immune system about which our research group has been working for several years.

  4. Biological effectiveness of antiproton annihilation

    CERN Document Server

    Holzscheiter, Michael H.; Bassler, Niels; Beyer, Gerd; De Marco, John J.; Doser, Michael; Ichioka, Toshiyasu; Iwamoto, Keisuke S.; Knudsen, Helge V.; Landua, Rolf; Maggiore, Carl; McBride, William H.; Møller, Søren Pape; Petersen, Jorgen; Smathers, James B.; Skarsgard, Lloyd D.; Solberg, Timothy D.; Uggerhøj, Ulrik I.; Withers, H.Rodney; Vranjes, Sanja; Wong, Michelle; Wouters, Bradly G.

    2004-01-01

    We describe an experiment designed to determine whether or not the densely ionizing particles emanating from the annihilation of antiprotons produce an increase in “biological dose” in the vicinity of the narrow Bragg peak for antiprotons compared to protons. This experiment is the first direct measurement of the biological effects of antiproton annihilation. The experiment has been approved by the CERN Research Board for running at the CERN Antiproton Decelerator (AD) as AD-4/ACE (Antiproton Cell Experiment) and has begun data taking in June of 2003. The background, description and the current status of the experiment are given.

  5. Biological effectiveness of antiproton annihilation

    DEFF Research Database (Denmark)

    Holzscheiter, M.H.; Agazaryan, N.; Bassler, Niels;

    2004-01-01

    We describe an experiment designed to determine whether or not the densely ionizing particles emanating from the annihilation of antiprotons produce an increase in ‘‘biological dose’’ in the vicinity of the narrow Bragg peak for antiprotons compared to protons. This experiment is the first direct...... measurement of the biological effects of antiproton annihilation. The experiment has been approved by the CERN Research Board for running at the CERN Antiproton Decelerator (AD) as AD-4/ACE (Antiproton Cell Experiment) and has begun data taking in June of 2003. The background, description and the current...

  6. Antineoplastic effect of iodine and iodide in dimethylbenz[a]anthracene-induced mammary tumors: association between lactoperoxidase and estrogen-adduct production.

    Science.gov (United States)

    Soriano, Ofelia; Delgado, Guadalupe; Anguiano, Brenda; Petrosyan, Pavel; Molina-Servín, Edith D; Gonsebatt, Maria E; Aceves, Carmen

    2011-08-01

    Several groups, including ours, have reported that iodine exhibited antiproliferative and apoptotic effects in various cancer cells only if this element is supplemented as molecular iodine, or as iodide, to cells that are able to oxidize it with the enzyme thyroperoxidase. In this study, we analyzed the effect of various concentrations of iodine and/or iodide in the dimethylbenz[a]anthracene (DMBA) mammary cancer model in rats. The results show that 0.1% iodine or iodide increases the expression of peroxisome proliferator-activated receptor type γ (PPARγ), triggering caspase-mediated apoptosis pathways in damaged mammary tissue (DMBA-treated mammary gland) as well as in frank mammary tumors, but not in normal mammary gland. DMBA treatment induces the expression of lactoperoxidase, which participates in the antineoplastic effect of iodide and could be involved in the pro-neoplastic effect of estrogens, increasing the formation of DNA adducts. In conclusion, our results show that a supplement of 0.1% molecular iodine/potassium iodide (0.05/0.05%) exert antineoplastic effects, preventing estrogen-induced DNA adducts and inducing apoptosis through PPARγ/caspases in pre-cancer and cancerous cells. Since this iodine concentration does not modify the cytology (histology, apoptosis rate) or physiology (triiodothyronine and thyrotropin) of the thyroid gland, we propose that it be considered as an adjuvant treatment for premenopausal mammary cancer.

  7. Decavanadate effects in biological systems.

    Science.gov (United States)

    Aureliano, Manuel; Gândara, Ricardo M C

    2005-05-01

    Vanadium biological studies often disregarded the formation of decameric vanadate species known to interact, in vitro, with high-affinity with many proteins such as myosin and sarcoplasmic reticulum calcium pump and also to inhibit these biochemical systems involved in energy transduction. Moreover, very few in vivo animal studies involving vanadium consider the contribution of decavanadate to vanadium biological effects. Recently, it has been shown that an acute exposure to decavanadate but not to other vanadate oligomers induced oxidative stress and a different fate in vanadium intracellular accumulation. Several markers of oxidative stress analyzed on hepatic and cardiac tissue were monitored after in vivo effect of an acute exposure (12, 24 h and 7 days), to a sub-lethal concentration (5 mM; 1 mg/kg) of two vanadium solutions ("metavanadate" and "decavanadate"). It was observed that "decavanadate" promote different effects than other vanadate oligomers in catalase activity, glutathione content, lipid peroxidation, mitochondrial superoxide anion production and vanadium accumulation, whereas both solutions seem to equally depress reactive oxygen species (ROS) production as well as total intracellular reducing power. Vanadium is accumulated in mitochondria in particular when "decavanadate" is administered. These recent findings, that are now summarized, point out the decameric vanadate species contributions to in vivo and in vitro effects induced by vanadium in biological systems.

  8. Effect of green tea catechins and hydrolyzable tannins on benzo[a]pyrene-induced DNA adducts and structure-activity relationship.

    Science.gov (United States)

    Cao, Pengxiao; Cai, Jian; Gupta, Ramesh C

    2010-04-19

    Green tea catechins and hydrolyzable tannins are gaining increasing attention as chemopreventive agents. However, their mechanism of action is poorly understood. We investigated the effects of four green tea catechins and two hydrolyzable tannins on microsome-induced benzo[a]pyrene (BP)-DNA adducts and the possible structure-activity relationship. BP (1 microM) was incubated with rat liver microsomes and DNA in the presence of the test compound (1-200 microM) or vehicle. The purified DNA was analyzed by (32)P-postlabeling. The inhibitory activity of the catechins was in the following descending order: epigallocatechin gallate (IC(50) = 16 microM) > epicatechin gallate (24 microM) > epigallocatechin (146 microM) > epicatechin (462 microM), suggesting a correlation between the number of adjacent aromatic hydroxyl groups in the molecular structure and their potencies. Tannic acid (IC(50) = 4 microM) and pentagalloglucose (IC(50) = 26 microM) elicited as much DNA adduct inhibitory activity as the catechins or higher presumably due to the presence of more functional hydroxyl groups. To determine if the activity of these compounds was due to direct interaction of phenolic groups with electrophilic metabolite(s) of BP, DNA was incubated with anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (anti-BPDE) (0.5 microM) in the presence of test compounds (200 microM) or vehicle. Significant inhibition of DNA adduct formation was found (tannic acid > pentagalloglucose > epigallocatechin gallate > epicatechin gallate). This notion was confirmed by analysis of the reaction products of anti-BPDE with the catechins and pentagalloglucose by electrospray ionization mass spectrometry and liquid chromatography-mass spectrometry. In conclusion, our data demonstrate that green tea catechins and the hydrolyzable tannins are highly effective in inhibiting BP-DNA adduct formation at least, in part, due to direct interaction of adjacent hydroxyl groups in their structures and that the activity is

  9. 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

  10. Quantum Effects in Biological Systems

    Science.gov (United States)

    Roy, Sisir

    2014-07-01

    The debates about the trivial and non-trivial effects in biological systems have drawn much attention during the last decade or so. What might these non-trivial sorts of quantum effects be? There is no consensus so far among the physicists and biologists regarding the meaning of "non-trivial quantum effects". However, there is no doubt about the implications of the challenging research into quantum effects relevant to biology such as coherent excitations of biomolecules and photosynthesis, quantum tunneling of protons, van der Waals forces, ultrafast dynamics through conical intersections, and phonon-assisted electron tunneling as the basis for our sense of smell, environment assisted transport of ions and entanglement in ion channels, role of quantum vacuum in consciousness. Several authors have discussed the non-trivial quantum effects and classified them into four broad categories: (a) Quantum life principle; (b) Quantum computing in the brain; (c) Quantum computing in genetics; and (d) Quantum consciousness. First, I will review the above developments. I will then discuss in detail the ion transport in the ion channel and the relevance of quantum theory in brain function. The ion transport in the ion channel plays a key role in information processing by the brain.

  11. Partitioning of knee joint internal forces in gait is dictated by the knee adduction angle and not by the knee adduction moment.

    Science.gov (United States)

    Adouni, M; Shirazi-Adl, A

    2014-05-01

    Medial knee osteoarthritis is a debilitating disease. Surgical and conservative interventions are performed to manage its progression via reduction of load on the medial compartment or equivalently its surrogate measure, the external adduction moment. However, some studies have questioned a correlation between the medial load and adduction moment. Using a musculoskeletal model of the lower extremity driven by kinematics-kinetics of asymptomatic subjects at gait midstance, we aim here to quantify the relative effects of changes in the knee adduction angle versus changes in the adduction moment on the joint response and medial/lateral load partitioning. The reference adduction rotation of 1.6° is altered by ±1.5° to 3.1° and 0.1° or the knee reference adduction moment of 17Nm is varied by ±50% to 25.5Nm and 8.5Nm. Quadriceps, hamstrings and tibiofemoral contact forces substantially increased as adduction angle dropped and diminished as it increased. The medial/lateral ratio of contact forces slightly altered by changes in the adduction moment but a larger adduction rotation hugely increased this ratio from 8.8 to a 90 while in contrast a smaller adduction rotation yielded a more uniform distribution. If the aim in an intervention is to diminish the medial contact force and medial/lateral load ratio, a drop of 1.5° in adduction angle is much more effective (causing respectively 12% and 80% decreases) than a reduction of 50% in the adduction moment (causing respectively 4% and 13% decreases). Substantial role of changes in adduction angle is due to the associated alterations in joint nonlinear passive resistance. These findings explain the poor correlation between knee adduction moment and tibiofemoral compartment loading during gait suggesting that the internal load partitioning is dictated by the joint adduction angle.

  12. Interactive effects of ultraviolet-B radiation and pesticide exposure on DNA photo-adduct accumulation and expression of DNA damage and repair genes in Xenopus laevis embryos

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Shuangying, E-mail: shuangying.yu@ttu.edu [Department of Environmental Toxicology, The Institute of Environmental and Human Health, Texas Tech University, 1207 S. Gilbert Dr., Lubbock, TX 79416 (United States); Tang, Song, E-mail: song.tang@usask.ca [Department of Environmental Toxicology, The Institute of Environmental and Human Health, Texas Tech University, 1207 S. Gilbert Dr., Lubbock, TX 79416 (United States); Mayer, Gregory D., E-mail: greg.mayer@ttu.edu [Department of Environmental Toxicology, The Institute of Environmental and Human Health, Texas Tech University, 1207 S. Gilbert Dr., Lubbock, TX 79416 (United States); Cobb, George P., E-mail: george_cobb@baylor.edu [Department of Environmental Science, Baylor University, One Bear Place #97266, Waco, TX 76798 (United States); Maul, Jonathan D., E-mail: jonathan.maul@ttu.edu [Department of Environmental Toxicology, The Institute of Environmental and Human Health, Texas Tech University, 1207 S. Gilbert Dr., Lubbock, TX 79416 (United States)

    2015-02-15

    Highlights: • Interactive effects of UVB radiation-pesticide co-exposures were examined in frogs. • Responses included induction of DNA photo-adducts and DNA damage and repair genes. • Elevated DNA adduct levels occurred for co-exposures compared to UVB alone. • One mechanism is that pesticides may alter nuclear excision repair gene expression. - Abstract: Pesticide use and ultraviolet-B (UVB) radiation have both been suggested to adversely affect amphibians; however, little is known about their interactive effects. One potential adverse interaction could involve pesticide-induced dysregulation of DNA repair pathways, resulting in greater numbers of DNA photo-adducts from UVB exposure. In the present study, we investigated the interactive effects of UVB radiation and two common pesticides (endosulfan and α-cypermethrin) on induction of DNA photo-adducts and expression of DNA damage and repair related genes in African clawed frog (Xenopus laevis) embryos. We examined 13 genes that are, collectively, involved in stress defense, cell cycle arrest, nucleotide excision repair (NER), base excision repair, mismatch repair, DNA repair regulation, and apoptosis. We exposed X. laevis embryos to 0, 25, and 50 μg/L endosulfan or 0, 2.5, and 5.0 μg/L α-cypermethrin for 96 h, with environmentally relevant exposures of UVB radiation during the last 7 h of the 96 h exposure. We measured the amount of cyclobutane pyrimidine dimers (CPDs) and mRNA abundance of the 13 genes among treatments including control, pesticide only, UVB only, and UVB and pesticide co-exposures. Each of the co-exposure scenarios resulted in elevated CPD levels compared to UVB exposure alone, suggesting an inhibitory effect of endosulfan and α-cypermethrin on CPD repair. This is attributed to results indicating that α-cypermethrin and endosulfan reduced mRNA abundance of XPA and HR23B, respectively, to levels that may affect the initial recognition of DNA lesions. In contrast, both pesticides

  13. Biological transformation, kinetics and dose-response assessments of bound musk ketone hemoglobin adducts in rainbow trout as biomarkers of environmental exposure

    Institute of Scientific and Technical Information of China (English)

    M A Mottaleb; J H Zimmerman; T W Moy

    2008-01-01

    Low levels (ng/g) of musk ketone (MK), used as a fragrance additive in the formulation of personal care products, are frequently detected in the water and other environment. Thus, aquatic organisms can be continuously exposed to MK. In this study, kinetics and dose-response assessments of 2-amino-MK (AMK) metabolite, bound to cysteine-hemoglobin (Hb) in rainbow trout, formed by enzymatic nitro-reduction of MK have been demonstrated. Trout were exposed to a single exposure of 0.010, 0.030, 0.10, and or 0.30 mg MK/g of fish. Twenty-six Hb samples were collected from exposed- and control fish subsequent to exposure intervals of 1 d (24 h), 3 d (72 h), and 7 d (168 h). Basic hydrolysis released bound AMK metabolite was extracted into n-hexane and then concentrated and analyzed by gas chromatography (GC) electron capture negative ion chemical ionization (NICI) mass spectrometry (MS) using selected ion monitoring (SIM). The presence of the AMK metabolite in Hb extracts was confirmed by agreement of similar mass spectral features and retention time with a standard. In the dose-response study, maximum adduct formation was obtained at the 0.10 mg/g dose with an average AMK metabolite concentration of 2.2 ng/g. For kinetics, the highest concentration of the AMK metabolite was found to be 32.0 ng/g at 0.03 mg/g dose in 3-d sample. Further elimination of the metabolite showed kinetics with a half-life estimated to be 2 d, assuming first-order kinetics. The metabolite was not detected in the control samples, non-hydrolyzed Hb, and reagent blank extracts. The detection limit for AMK in the Hb was approximately 0.30 (g/L, based on a signal to noise ratio of 3 (S/N = 3).

  14. Investigation of the DNA adducts formed in B6C3F1 mice treated with benzene: Implications for molecular dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Bodell, W.J.; Pathak, D.N.; Levay, G. [Univ. of California, San Francisco, CA (United States)] [and others

    1996-12-01

    We have investigated the formation of DNA adducts in the bone marrow and white blood cells of male B6C3F1 mice treated with benzene using P1-enhanced {sup 32}P-postlabeling. No adducts were detected in the bone marrow of controls or mice treated with various doses of benzene once a day. After twice-daily treatment for 1 to 7 days with benzene, 440 mg/kg, one major (no. 1) and UP to two minor DNA adducts were detected in both the bone marrow and white blood cells. The relative adduct levels in these cells ranged from 0.06 to 1.46 x 10{sup -7}. A significant correlation (r 0.95) between levels of adducts in bone marrow and white blood cells was observed. After a 7-day treatment with benzene, 440 mg/kg twice a day, the number of cells per femur decreased from 1.6 x 10{sup 7} to 0.85 X 10{sup 7}, indicating myelotoxicity. In contrast, administration of benzene once a day produced only a small decrease in bone marrow cellularity. The observed induction of toxicity in bone marrow was paralleled by formation of DNA adducts. In vitro treatment of bone marrow with hydroquinone (HQ) for 24 hr produced the same DNA adducts as found after treatment of mice with benzene, suggesting that HQ is the principal metabolite of benzene leading to DNA adduct formation in vivo. Using {sup 32}P-postlabeling the principal DNA adduct formed in vivo was compared with N{sup 2}-(4-hydroxyphenyl)-2-deoxyguanosine-3-phosphate. The results of this comparison demonstrates that the DNA adduct formed in vivo co-chromatographs with N{sup 2}-(4-hydroxyphenyl)-2-deoxyguanosine-3{prime}-phosphate. These studies indicate that metabolic activation of benzene leads to the formation of DNA adducts in bone marrow and white blood cells and suggest that measurement of DNA adducts in white blood cells may be an indicator of biological effect following benzene exposure. 34 refs., 4 figs., 2 tabs.

  15. The antimicrobial activities of the cinnamaldehyde adducts with amino acids.

    Science.gov (United States)

    Wei, Qing-Yi; Xiong, Jia-Jun; Jiang, Hong; Zhang, Chao; Wen Ye

    2011-11-01

    Cinnamaldehyde is a well-established natural antimicrobial compound. It is probable for cinnamaldehyde to react with amino acid forming Schiff base adduct in real food system. In this paper, 9 such kind of adducts were prepared by the direct reaction of amino acids with cinnamaldehyde at room temperature. Their antimicrobial activities against Bacillus subtilis, Escherichia coli and Saccharomyces cerevisiae were evaluated with benzoic acid as a reference. The adducts showed a dose-dependent activities against the three microbial strains. Both cinnamaldehyde and their adducts were more active against B. subtilis than on E. coli, and their antimicrobial activities were higher at lower pH. Both cinnamaldehyde and its adducts were more active than benzoic acid at the same conditions. The adduct compound A was non-toxic by primary oral acute toxicity study in mice. However, in situ effect of the adduct compound A against E. coli was a little lower than cinnamaldehyde in fish meat. This paper for the first time showed that the cinnamaldehyde adducts with amino acids had similar strong antimicrobial activities as cinnamaldehyde, which may provide alternatives to cinnamaldehyde in food to avoid the strong unacceptable odor of cinnamaldehyde.

  16. Reactive Carbonyl Species In Vivo: Generation and Dual Biological Effects

    Directory of Open Access Journals (Sweden)

    Halyna M. Semchyshyn

    2014-01-01

    Full Text Available Reactive carbonyls are widespread species in living organisms and mainly known for their damaging effects. The most abundant reactive carbonyl species (RCS are derived from oxidation of carbohydrates, lipids, and amino acids. Chemical modification of proteins, nucleic acids, and aminophospholipids by RCS results in cytotoxicity and mutagenicity. In addition to their direct toxicity, modification of biomolecules by RCS gives rise to a multitude of adducts and cross links that are increasingly implicated in aging and pathology of a wide range of human diseases. Understanding of the relationship between metabolism of RCS and the development of pathological disorders and diseases may help to develop effective approaches to prevent a number of disorders and diseases. On the other hand, constant persistence of RCS in cells suggests that they perform some useful role in living organisms. The most beneficial effects of RCS are their establishment as regulators of cell signal transduction and gene expression. Since RCS can modulate different biological processes, new tools are required to decipher the precise mechanisms underlying dual effects of RCS.

  17. Alcohol, Aldehydes, Adducts and Airways.

    Science.gov (United States)

    Sapkota, Muna; Wyatt, Todd A

    2015-11-05

    Drinking alcohol and smoking cigarettes results in the formation of reactive aldehydes in the lung, which are capable of forming adducts with several proteins and DNA. Acetaldehyde and malondialdehyde are the major aldehydes generated in high levels in the lung of subjects with alcohol use disorder who smoke cigarettes. In addition to the above aldehydes, several other aldehydes like 4-hydroxynonenal, formaldehyde and acrolein are also detected in the lung due to exposure to toxic gases, vapors and chemicals. These aldehydes react with nucleophilic targets in cells such as DNA, lipids and proteins to form both stable and unstable adducts. This adduction may disturb cellular functions as well as damage proteins, nucleic acids and lipids. Among several adducts formed in the lung, malondialdehyde DNA (MDA-DNA) adduct and hybrid malondialdehyde-acetaldehyde (MAA) protein adducts have been shown to initiate several pathological conditions in the lung. MDA-DNA adducts are pre-mutagenic in mammalian cells and induce frame shift and base-pair substitution mutations, whereas MAA protein adducts have been shown to induce inflammation and inhibit wound healing. This review provides an insight into different reactive aldehyde adducts and their role in the pathogenesis of lung disease.

  18. Interactive effects of ultraviolet-B radiation and pesticide exposure on DNA photo-adduct accumulation and expression of DNA damage and repair genes in Xenopus laevis embryos.

    Science.gov (United States)

    Yu, Shuangying; Tang, Song; Mayer, Gregory D; Cobb, George P; Maul, Jonathan D

    2015-02-01

    Pesticide use and ultraviolet-B (UVB) radiation have both been suggested to adversely affect amphibians; however, little is known about their interactive effects. One potential adverse interaction could involve pesticide-induced dysregulation of DNA repair pathways, resulting in greater numbers of DNA photo-adducts from UVB exposure. In the present study, we investigated the interactive effects of UVB radiation and two common pesticides (endosulfan and α-cypermethrin) on induction of DNA photo-adducts and expression of DNA damage and repair related genes in African clawed frog (Xenopus laevis) embryos. We examined 13 genes that are, collectively, involved in stress defense, cell cycle arrest, nucleotide excision repair (NER), base excision repair, mismatch repair, DNA repair regulation, and apoptosis. We exposed X. laevis embryos to 0, 25, and 50 μg/L endosulfan or 0, 2.5, and 5.0 μg/L α-cypermethrin for 96 h, with environmentally relevant exposures of UVB radiation during the last 7 h of the 96 h exposure. We measured the amount of cyclobutane pyrimidine dimers (CPDs) and mRNA abundance of the 13 genes among treatments including control, pesticide only, UVB only, and UVB and pesticide co-exposures. Each of the co-exposure scenarios resulted in elevated CPD levels compared to UVB exposure alone, suggesting an inhibitory effect of endosulfan and α-cypermethrin on CPD repair. This is attributed to results indicating that α-cypermethrin and endosulfan reduced mRNA abundance of XPA and HR23B, respectively, to levels that may affect the initial recognition of DNA lesions. In contrast, both pesticides increased transcript abundance of CSA and MUTL. In addition, mRNA abundance of HSP70 and GADD45α were increased by endosulfan and mRNA abundance of XPG was increased by α-cypermethrin. XPC, HR23B, XPG, and GADD45α exhibited elevated mRNA concentrations whereas there was a reduction in MUTL transcript concentrations in UVB-alone treatments. It appeared that even

  19. [Biological effect of wood dust].

    Science.gov (United States)

    Maciejewska, A; Wojtczak, J; Bielichowska-Cybula, G; Domańska, A; Dutkiewicz, J; Mołocznik, A

    1993-01-01

    The biological effect of exposure to wood dust depends on its composition and the content of microorganisms which are an inherent element of the dust. The irritant and allergic effects of wood dust have been recognised for a long time. The allergic effect is caused by the wood dust of subtropical trees, e.g. western red cedar (Thuja plicata), redwood (Sequoia sempervirens), obeche (Triplochiton scleroxylon), cocabolla (Dalbergia retusa) and others. Trees growing in the European climate such as: larch (Larix), walnut (Juglans regia), oak (Quercus), beech (Fagus), pine (Pinus) cause a little less pronounced allergic effect. Occupational exposure to irritative or allergic wood dust may lead to bronchial asthma, rhinitis, alveolitis allergica, DDTS (Organic dust toxic syndrome), bronchitis, allergic dermatitis, conjunctivitis. An increased risk of adenocarcinoma of the sinonasal cavity is an important and serious problem associated with occupational exposure to wood dust. Adenocarcinoma constitutes about half of the total number of cancers induced by wood dust. An increased incidence of the squamous cell cancers can also be observed. The highest risk of cancer applies to workers of the furniture industry, particularly those dealing with machine wood processing, cabinet making and carpentry. The cancer of the upper respiratory tract develops after exposure to many kinds of wood dust. However, the wood dust of oak and beech seems to be most carcinogenic. It is assumed that exposure to wood dust can cause an increased incidence of other cancers, especially lung cancer and Hodgkin's disease. The adverse effects of microorganisms, mainly mould fungi and their metabolic products are manifested by alveolitis allergica and ODTS. These microorganisms can induce aspergillomycosis, bronchial asthma, rhinitis and allergic dermatitis.

  20. Biological effects of drilling wastes

    Energy Technology Data Exchange (ETDEWEB)

    Cranford, P. J. [Department of Fisheries and Oceans, Dartmouth, NS (Canada). Bedford Inst. of Oceanography

    2000-07-01

    An argument is made for the point of view that economic realities require that a sustainable fishery must co-exist with the offshore petroleum industry, and therefore to sustain the fishery comprehensive studies are needed to identify and minimize the impact of operational drilling wastes on fishery resources. Moreover, laboratory and field studies indicate that operational drilling platforms impact on fisheries at great distances, therefore studies should not be limited to the immediate vicinity of drilling sites. Studies on long-term exposure of resident organisms to low level contaminants and the chronic lethal and sublethal biological effects of production drilling wastes must be conducted under environmentally relevant conditions to ensure the validity of the results. Studies at the Bedford Institute of Oceanography on sea scallops (Placopecten magellanicus) shows them to be highly sensitive to impacts from drilling wastes. Results of these studies, integrated with toxicity data and information on the distribution and transport of drilling wastes have been used by regulatory agencies and industrial interests to develop scientifically sound and justifiable regulations. They also led to the development of practical, sensitive and cost-effective technologies that use resident resource species to detect environmental impacts at offshore production sites. 1 fig.

  1. Formation of a major DNA adduct of the mitomycin metabolite 2,7-diaminomitosene in EMT6 mouse mammary tumor cells treated with mitomycin C.

    Science.gov (United States)

    Palom, Y; Belcourt, M F; Kumar, G S; Arai, H; Kasai, M; Sartorelli, A C; Rockwell, S; Tomasz, M

    1998-01-01

    Treatment of EMT6 mouse mammary tumor cells with [3H]mitomycin C (MC) results in the formation of six major DNA adducts, as described earlier using an HPLC assay of 3H-labeled products of enzymatic hydrolysis of DNA isolated from MC-treated cells. Four of these adducts were identified as monofunctional and bifunctional guanine-N2 adducts in the minor groove of DNA. In order to establish relationships between individual types of MC-DNA adducts and biological responses it is necessary to identify all of the adducts formed in cells. To this end we have now identified a predominant, previously unknown adduct formed in MC-treated EMT6 cells as a derivative not of MC, but of 2,7-diaminomitosene (2,7-DAM), the major bioreductive metabolite of MC. Rigorous proof demonstrates that it is a DNA major groove, guanine-N7 adduct of 2,7-DAM, linked at C-10 to DNA. The adduct is relatively stable at ambient temperature, but is readily depurinated upon heating. Its isolation from MC-treated cells indicates that MC is reductively metabolized to 2,7-DAM, which then undergoes further reductive activation to alkylate DNA, along with the parent MC. Low MC:DNA ratios were identified as a critical factor promoting 2,7-DAM adduct formation in an in vitro model calf thymus DNA/ MC/reductase model system, as well as in MC-treated EMT6 cells. The 2,7-DAM-guanine-N7 DNA adduct appears to be relatively noncytotoxic, as indicated by the dramatically lower cytotoxicity of 2,7-DAM in comparison with MC in EMT6 cells. Like MC, 2,7-DAM exhibited slightly greater cytotoxicity to cells treated under hypoxic as compared to aerobic conditions. However, 2,7-DAM was markedly less cytotoxic than MC under both aerobic and hypoxic conditions. Thus, metabolic reduction of MC to 2,7-DAM represents a detoxification process. The differential effects of MC-DNA and 2,7-DAM-DNA adducts support the concept that specific structural features of the DNA damage may play a critical role in the cytotoxic response to a DNA

  2. PAH-DNA adducts in cord blood and fetal and child development in a Chinese cohort

    Energy Technology Data Exchange (ETDEWEB)

    Tang, D.L.; Li, T.Y.; Liu, J.J.; Chen, Y.H.; Qu, L.R.; Perera, F. [Columbia University, New York, NY (United States). Dept. for Environmental Health Science

    2006-08-15

    Polycyclic aromatic hydrocarbons (PAHs) are an important class of toxic pollutants released by fossil fuel combustion. Other pollutants include metals and particulate matter. PAH-DNA adducts, or benzo(a)pyrene (BaP) adducts as their proxy, provide a chemical-specific measure of individual biologically effective doses that have been associated with increased risk of cancer and adverse birth outcomes. In the present study we examined the relationship between prenatal PAH exposure and fetal and child growth and development in Tongliang, China, where a seasonally operated coal-fired power plant was the major pollution source. In a cohort of 150 nonsmoking women and their newborns enrolled between 4 March 2002 and 19 June 2002, BaP-DNA adducts were measured in maternal and umbilical cord blood obtained at delivery. High PAH-DNA adduct levels (above the median of detectable adduct level) were associated with decreased birth head circumference (p = 0.057) and reduced children's weight at 18 months, 24 months, and 30 months of age (p {lt} 0.05), after controlling for potential confounders. In addition, in separate models, longer duration of prenatal exposure was associated with reduced birth length (p = 0.033) and reduced children's height at 18 (p = 0.001), 24 (p {lt} 0.001), and 30 months of age (p {lt} 0.001). The findings suggest that exposure to elevated levels of PAHS, with the Tongliang power plant being a significant source, is associated with reduced fetal and child growth in this population.

  3. Effect of multiple adduct fullerenes on microstructure and phase behavior of P3HT:fullerene blend films for organic solar cells.

    Science.gov (United States)

    Guilbert, Anne A Y; Reynolds, Luke X; Bruno, Annalisa; MacLachlan, Andrew; King, Simon P; Faist, Mark A; Pires, Ellis; Macdonald, J Emyr; Stingelin, Natalie; Haque, Saif A; Nelson, Jenny

    2012-05-22

    The bis and tris adducts of [6,6]phenyl-C(61)-butyric acid methyl ester (PCBM) offer lower reduction potentials than PCBM and are therefore expected to offer larger open-circuit voltages and more efficient energy conversion when blended with conjugated polymers in photovoltaic devices in place of PCBM. However, poor photovoltaic device performances are commonly observed when PCBM is replaced with higher-adduct fullerenes. In this work, we use transmission electron microscopy (TEM), steady-state and ultrafast time-resolved photoluminescence spectroscopy (PL), and differential scanning calorimetry (DSC) to probe the microstructural properties of blend films of poly(3-hexylthiophene-2,5-diyl) (P3HT) with the bis and tris adducts of PCBM. TEM and PL indicate that, in as-spun blend films, fullerenes become less soluble in P3HT as the number of adducts increases. PL indicates that upon annealing crystallization leads to phase separation in P3HT:PCBM samples only. DSC studies indicate that the interactions between P3HT and the fullerene become weaker with higher-adduct fullerenes and that all systems exhibit eutectic phase behavior with a eutectic composition being shifted to higher molar fullerene content for higher-adduct fullerenes. We propose two different mechanisms of microstructure development for PCBM and higher-adduct fullerenes. P3HT:PCBM blends, phase segregation is the result of crystallization of either one or both components and is facilitated by thermal treatments. In contrast, for blends containing higher adducts, the phase separation is due to a partial demixing of the amorphous phases. We rationalize the lower photocurrent generation by the higher-adduct fullerene blends in terms of film microstructure.

  4. Strategy for identifying unknown hemoglobin adducts using adductome LC-MS/MS data: Identification of adducts corresponding to acrylic acid, glyoxal, methylglyoxal, and 1-octen-3-one.

    Science.gov (United States)

    Carlsson, Henrik; Törnqvist, Margareta

    2016-06-01

    Electrophilic compounds have the ability to form adducts with nucleophilic sites in proteins and DNA in tissues, and thereby constitute risks for toxic effects. Adductomic approaches are developed for systematic screening of adducts to DNA and blood proteins, with the aim to detect unknown internal exposures to electrophiles. In a previous adductomic screening of adducts to N-terminals in hemoglobin, using LC-MS/MS, 19 unknown adducts were detected in addition to seven previously identified adducts. The present paper describes the identification of four of these unknown adducts, as well as the strategy used to identify them. Using LC-MS data from the screening, hypotheses about adduct identities were formulated: probable precursor electrophiles with matching molecular weights were suggested based on the molecular weights of the modifications and the retention times of the analytes, in combination with comparisons of theoretical Log P calculations and databases. Reference adducts were generated by incubation of blood samples with the hypothesized precursor electrophiles. The four identified precursor electrophiles, corresponding to the observed unknown adducts, were glyoxal, methylglyoxal, acrylic acid and 1-octen-3-one. Possible origins/exposure sources and toxicological information concerning the electrophilic precursors are discussed. The identified adducts could be explored as possible biomarkers for exposure.

  5. Base sequence effects on DNA replication influenced by bulky adducts. Final report, March 1, 1995--February 28, 1997

    Energy Technology Data Exchange (ETDEWEB)

    Geacintov, N.E.

    1997-05-31

    Polycyclic aromatic hydrocarbons (PAH) are environmental pollutants that are present in air, food, and water. While PAH compounds are chemically inert and are sparingly soluble in aqueous solutions, in living cells they are metabolized to a variety of oxygenated derivatives, including the high mutagenic and tumorigenic diol epoxide derivatives. The diol epoxides of the sterically hindered fjord region compound benzo[c]phenanthrene (B[c]PhDE) are among the most powerful tumorigenic compounds in animal model test systems. In this project, site-specifically modified oligonucleotides containing single B[c]PhDE-N{sup 6}-dA lesions derived from the reactions of the 1S,2R,3R,4S and 1R,2S,3S,4R diol epoxides of B[c]PhDE with dA residues were synthesized. The replication of DNA catalyzed by a prokaryotic DNA polymerase (the exonuclease-free Klenow fragment E. Coli Po1 I) in the vicinity of the lesion at base-specific sites on B[c]PhDE-modified template strands was investigated in detail. The Michaelis-Menten parameters for the insertion of single deoxynucleotide triphosphates into growing DNA (primer) strands using the modified dA* and the bases just before and after the dA* residue as templates, depend markedly on the stereochemistry of the B[c]PhDE-modified dA residues. These observations provide novel insights into the mechanisms by which bulky PAH-DNA adducts affect normal DNA replication.

  6. Biological significance of DNA adducts: comparison of increments over background for various biomarkers of genotoxicity in L5178Y tk(+/-) mouse lymphoma cells treated with hydrogen peroxide and cumene hydroperoxide.

    Science.gov (United States)

    Brink, Andreas; Richter, Ingrid; Lutz, Ursula; Wanek, Paul; Stopper, Helga; Lutz, Werner K

    2009-08-01

    DNA is affected by background damage of the order of one lesion per one hundred thousand nucleotides, with depurination and oxidative damage accounting for a major part. This damage contributes to spontaneous mutation and cancer. DNA adducts can be measured with high sensitivity, with limits of detection lower than one adduct per one billion nucleotides. Minute exposures to an exogenous DNA-reactive agent may therefore result in measurable adduct formation, although, as an increment over total DNA damage, a small increment in mutation cannot be measured and would be considered negligible. Here, we investigated whether this discrepancy also holds for adducts that are present as background induced by oxidative stress. L5178Y tk(+/-) mouse lymphoma cells were incubated for 4h with hydrogen peroxide (0, 0.8, 4, 20, 100, 500muM) or cumene hydroperoxide (0, 0.37, 1.1, 3.3, 10muM). Five endpoints of genotoxicity were measured in parallel from aliquots of three replicates of large batches of cells: Two DNA adducts, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and 1,N(6)-etheno-2'-deoxyadenosine (varepsilondAdo) measured by LC-MS/MS, as well as strand breaks assessed with the comet assay and in vitro micronucleus test, and gene mutation as assessed using the thymidine kinase gene mutation assay. Background measures of 8-oxodGuo and varepsilondAdo were 500-1000 and 50-90 adducts per 10(9) nucleotides. Upon treatment, neither hydrogen peroxide nor cumene hydroperoxide significantly increased the DNA adduct levels above control. In contrast, dose-related increases above background were observed with both oxidants in the comet assay, the micronucleus test and the gene mutation assay. Differences in sensitivity of the assays were quantified by estimating the concentration of oxidant that resulted in a doubling of the background measure. We conclude that the increase in DNA breakage and mutation induced by hydrogen peroxide and cumene hydroperoxide observed in our in vitro

  7. Acetaldehyde Adducts in Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Mashiko Setshedi

    2010-01-01

    Full Text Available Chronic alcohol abuse causes liver disease that progresses from simple steatosis through stages of steatohepatitis, fibrosis, cirrhosis, and eventually hepatic failure. In addition, chronic alcoholic liver disease (ALD, with or without cirrhosis, increases risk for hepatocellular carcinoma (HCC. Acetaldehyde, a major toxic metabolite, is one of the principal culprits mediating fibrogenic and mutagenic effects of alcohol in the liver. Mechanistically, acetaldehyde promotes adduct formation, leading to functional impairments of key proteins, including enzymes, as well as DNA damage, which promotes mutagenesis. Why certain individuals who heavily abuse alcohol, develop HCC (7.2–15% versus cirrhosis (15–20% is not known, but genetics and co-existing viral infection are considered pathogenic factors. Moreover, adverse effects of acetaldehyde on the cardiovascular and hematologic systems leading to ischemia, heart failure, and coagulation disorders, can exacerbate hepatic injury and increase risk for liver failure. Herein, we review the role of acetaldehyde adducts in the pathogenesis of chronic ALD and HCC.

  8. Biological effects of high LET radiations

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Masami [Nagasaki Univ. (Japan). Faculty of Pharmaceutical Sciences

    1997-03-01

    Biological effect of radiation is different by a kind of it greatly. Heavy ions were generally more effective in cell inactivation, chromosome aberration induction, mutation induction and neoplastic cell transformation induction than {gamma}-rays in SHE cells. (author)

  9. Correlation Effects in Biological Networks

    Directory of Open Access Journals (Sweden)

    A.A. Bagdasaryan

    2012-06-01

    Full Text Available Review of the complex network theory is presented and classification of such networks in accordance with the main statistical characteristics is considered. For the adjacency matrix of a real neural network the shortest distances for each pair of nodes as well as the node degree distribution and cluster coefficients are calculated. Comparison of the main statistical parameters with the random network is performed, and based on this, the conclusions about the correlation phenomena in biological system are made.

  10. Comparison of EMG activity on abdominal muscles during plank exercise with unilateral and bilateral additional isometric hip adduction.

    Science.gov (United States)

    Kim, Soo-Yong; Kang, Min-Hyeok; Kim, Eui-Ryong; Jung, In-Gui; Seo, Eun-Young; Oh, Jae-Seop

    2016-10-01

    The aim of this study was to investigate the effects of additional isometric hip adduction during the plank exercise on the abdominal muscles. Twenty healthy young men participated in this study. Surface electromyography (EMG) was used to monitor the activity of the bilateral rectus abdominis (RA), the internal oblique (IO), and the external oblique (EO) muscles. The participants performed three types of plank exercise; the standard plank exercise, the plank exercise with bilateral isometric hip adduction, and the plank exercise with unilateral isometric hip adduction. All abdominal muscle activity was significantly increased during the plank exercise combined with the bilateral and unilateral isometric hip adduction compared with the standard plank exercise (pmuscle activity was significantly increased during the unilateral isometric hip adduction compared with the bilateral isometric hip adduction (pabdominal muscle activity. In particular, the unilateral isometric hip adduction is a more beneficial exercise than the bilateral isometric hip adduction.

  11. Stable acetaldehyde--protein adducts as biomarkers of alcohol exposure.

    Science.gov (United States)

    Conduah Birt, J E; Shuker, D E; Farmer, P B

    1998-02-01

    The consumption of alcoholic beverages has been associated with increased risks of a number of chronic disorders including cancers. It is still not clear whether ethyl alcohol or other components such as metabolites are directly involved in the carcinogenic process or whether the effects are due to the modulation of metabolism of other carcinogens. At present, there is no good biomarker of alcohol intake, particularly at low or moderate levels of consumption. A number of studies have shown the ability of the major metabolite acetaldehyde to react with proteins in vitro to give stable and unstable adducts. The interaction of acetaldehyde with model peptides, which correspond to N-terminal globin sequences, was studied. The major stable adduct was identified by mass spectrometry and NMR as a diastereoisomeric mixture of imidazolidinones. This is believed to be formed by reaction and cyclization of the initial Schiff base adduct with the N-terminal valine. Incubation of human globin with acetaldehyde (0-2 mM) yielded products which were identified as the N-terminal adducts by electrospray ionization mass spectrometry (ESI-MS) of proteolytic digests. The specificity and sensitivity of the analysis was improved by the use of on-line HPLC-ESI-MS. Tryptic digests of the modified globin which contained both the N-terminal acetaldehyde adducts of alpha-globin (heptapeptide) and beta-globin (octapeptide) were resolved. These results suggest that analysis of stable imidazolidinone adducts is a promising approach to estimation of alcohol exposure.

  12. Effect of increased intake of dietary animal fat and fat energy on oxidative damage, mutation frequency, DNA adduct level and DNA repair in rat colon and liver

    DEFF Research Database (Denmark)

    Vogel, Ulla; Daneshvar, Bahram; Autrup, Herman;

    2003-01-01

    was observed. Intake of lard fat resulted in increased ascorbate synthesis and affected markers of oxidative damage to proteins in liver cytosol, but not in plasma. The effect was observed at all lard doses and was not dose-dependent. However, no evidence of increased oxidative DNA damage was found in liver...... supplemented with 0, 3, 10 or 30% w/w lard. After 3 weeks, the mutation frequency, DNA repair gene expression, DNA damage and oxidative markers were determined in liver, colon and plasma. The mutation frequency of the lambda gene cII did not increase with increased fat or energy intake in colon or liver....... The DNA-adduct level measured by 32P-postlabelling decreased in both liver and colon with increased fat intake. In liver, this was accompanied by a 2-fold increase of the mRNA level of nucleotide excision repair (NER) gene ERCC1. In colon, a non-statistically significant increase in the ERCC1 mRNA levels...

  13. Effect of increased intake of dietary animal fat and fat energy on oxidative damage, mutation frequency, DNA adduct level and DNA repair in rat colon and liver

    DEFF Research Database (Denmark)

    Vogel, Ulla Birgitte; Danesvar, B.; Autrup, H.;

    2003-01-01

    was observed. Intake of lard fat resulted in increased ascorbate synthesis and affected markers of oxidative damage to proteins in liver cytosol, but not in plasma. The effect was observed at all lard doses and was not dose-dependent. However, no evidence of increased oxidative DNA damage was found in liver...... supplemented with 0, 3, 10 or 30% w/w lard. After 3 weeks, the mutation frequency, DNA repair gene expression, DNA damage and oxidative markers were determined in liver, colon and plasma. The mutation frequency of the lambda gene cII did not increase with increased fat or energy intake in colon or liver....... The DNA-adduct level measured by P-32-postlabelling decreased in both liver and colon with increased fat intake. In liver, this was accompanied by a 2-fold increase of the mRNA level of nucleotide excision repair (NER) gene ERCC1. In colon, a non-statistically significant increase in the ERCC1 mRNA levels...

  14. Characterization of a Hemoglobin Adduct from Ethyl Vinyl Ketone Detected in Human Blood Samples.

    Science.gov (United States)

    Carlsson, Henrik; Motwani, Hitesh V; Osterman Golkar, Siv; Törnqvist, Margareta

    2015-11-16

    Electrophiles have the ability to form adducts to nucleophilic sites in proteins and DNA. Internal exposure to such compounds thus constitutes a risk for toxic effects. Screening of adducts using mass spectrometric methods by adductomic approaches offers possibilities to detect unknown electrophiles present in tissues. Previously, we employed untargeted adductomics to detect 19 unknown adducts to N-terminal valine in hemoglobin (Hb) in human blood. This article describes the characterization of one of these adducts, which was identified as the adduct from ethyl vinyl ketone (EVK). The mean adduct level was 40 ± 12 pmol/g Hb in 12 human blood samples; adduct levels from acrylamide (AA) and methyl vinyl ketone (MVK) were quantified for comparison. Using l-valine p-nitroanilide (Val-pNA), introduced as a model of the N-terminal valine, the rate of formation of the EVK adduct was studied, and the rate constant determined to 200 M(-1)h(-1) at 37 °C. In blood, the reaction rate was too fast to be feasibly measured, EVK showing a half-life adduct was found to be unstable, with a half-life of 7.6 h. From the mean adduct level measured in human blood, a daily dose (area under the concentration-time-curve, AUC) of 7 nMh EVK was estimated. The AUC of AA from intake via food is about 20 times higher. EVK is naturally present in a wide range of foods and is also used as a food additive. Most probably, naturally formed EVK is a major source to observed adducts. Evaluation of available toxicological data and information on occurrence of EVK indicate that further studies of EVK are motivated. This study illustrates a quantitative strategy in the initial evaluation of the significance of an adduct detected through adduct screening.

  15. Charge transfer adducts of metal complexes of π-donor ligands with I 2 and TCNQ

    Science.gov (United States)

    Bera, T. R.; Sen, D.; Ghosh, R.

    1989-01-01

    Copper(II) and nickel(II) biguanides and O-alkyl-1-amidinourea can act as donors for the formation of charge transfer (CT) adducts with I 2 and tetracyanoquinodimethane (TNCQ) as acceptors. Iodine adducts are characterized both in solid and solution states whereas TCNQ adducts obtain only in solution. Appearance of a broad band at 355 nm for iodine adducts and at 335 nm for TNCQ adducts and shifting of i.r. frequencies support the formation of donor acceptor associates. Elemental analysis establishes 1:1 stoichiometry of the solid adducts. The K and ɛ values determined by modified Benesi—Hildebrand, Scott and Rose—Drago equations are found to be of the order of 10 4 and 10 3 respectively at 298 K in methanol. The solvent effect on the K values is discussed in terms of coupled solute-solute and solute-solvent equilibria.

  16. Adduct formation in liquid chromatography-triple quadrupole mass spectrometric measurement of bryostatin 1.

    Science.gov (United States)

    Nelson, Thomas J; Sen, Abhik; Alkon, Daniel L; Sun, Miao-Kun

    2014-01-01

    Bryostatin 1, a potential anti-Alzheimer drug, is effective at subnanomolar concentrations. Measurement is complicated by the formation of low m/z degradation products and the formation of adducts with various cations, which make accurate quantitation difficult. Adduct formation caused the sample matrix or mobile phase to partition bryostatin 1 into products of different mass. Degradation of the 927 [M+Na](+) ion to a 869m/z product was strongly influenced by ionization conditions. We validated a bryostatin 1 assay in biological tissues using capillary column HPLC with nanospray ionization (NSI) in a triple-quadrupole mass spectrometer in selected reaction monitoring (SRM) mode. Adduct formation was controlled by adding 1mM acetic acid and 0.1mM sodium acetate to the HPLC buffer, maximizing the formation of the [M+Na](+) ion. Efficient removal of contaminating cholesterol from the sample during solvent extraction was also critical. The increased sensitivity provided by NSI and capillary-bore columns and the elimination of signal partitioning due to adduct formation and degradation in the ionization source enabled a detection limit of 1×10(-18)mol of bryostatin 1 and a LLOQ of 3×10(-18)mol from 1μl of sample. Bryostatin 1 at low pmol/l concentrations enabled measurement in brain and other tissues without the use of radioactive labels. Despite bryostatin 1's high molecular weight, considerable brain access was observed, with peak brain concentrations exceeding 8% of the peak blood plasma concentrations. Bryostatin 1 readily crosses the blood-brain barrier, reaching peak concentrations of 0.2nM, and specifically activates and translocates brain PKCɛ.

  17. Biological effects of ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Blaylock, B.G. [SENES Oak Ridge Inc., Oak Ridge, TN (United States); Theodorakis, C.W.; Shugart, L.R. [Oak Ridge National Lab., Oak Ridge, TN (United States). Environmental Sciences Division

    1996-12-31

    Natural populations have always been exposed to background levels of ionizing radiation; however, with the event of the nuclear age, studies about the effects of higher-than-background levels of ionizing radiation on individuals or populations of organisms became important. Originally, concern was focused on survival after large, acute radiation doses, and numerous studies document the somatic and genetic effects of acute ionizing radiation. However, there is a growing realization that chronic long-term exposure to higher-than-background levels of environmental radiation is more likely than is large acute exposure. Less than 10% of the literature on ionizing radiation effects deals with chronic long-term effects, and very few studies involve natural populations. In 1977, mosquito fish, Gambusia affinis, were experimentally introduced into a 0,45 ha, decommissioned, radioactive waste pond where the measured dose at the sediment-water interface was 1,150 rad/year. One year later, the fecundity of the population had not changed significantly. Eighteen years later, studies of the fish showed an inverse correlation between DNA strand breakage and fecundity in the contaminated pond. More recent studies have provided evidence that genetic diversity of the fish has increased in the contaminated site. These fish also have a greater prevalence of certain DNA banding patterns. Individuals displaying these banding patterns have a higher fecundity and lower degree of DNA strand breakage than individuals with less common banding patterns. Gambusia affinis has apparently adapted to the high background radiation, successfully surviving for approximately 50 generations. 31 refs, 5 figs.

  18. Biological Effects of Low-Dose Exposure

    CERN Document Server

    Komochkov, M M

    2000-01-01

    On the basis of the two-protection reaction model an analysis of stochastic radiobiological effects of low-dose exposure of different biological objects has been carried out. The stochastic effects are the results published in the last decade: epidemiological studies of human cancer mortality, the yield of thymocyte apoptosis of mice and different types of chromosomal aberrations. The results of the analysis show that as dependent upon the nature of biological object, spontanous effect, exposure conditions and radiation type one or another form dose - effect relationship is realized: downwards concave, near to linear and upwards concave with the effect of hormesis included. This result testifies to the incomplete conformity of studied effects of 1990 ICRP recomendations based on the linear no-threshold hypothesis about dose - effect relationship. Because of this the methodology of radiation risk estimation recomended by ICRP needs more precisian and such quantity as collective dose ought to be classified into...

  19. Biological Effect of Magnetic Field in Mice

    Institute of Scientific and Technical Information of China (English)

    Zhao-Wei ZENG

    2005-01-01

    Objective: To study the biological effect of magnetic field in mice bodies. Method: With a piece of permanent magnet embeded in mice bodies beside the femoral artery and vein to measure the electrophoretic velocity(um/s). Result: The magnetic field in mice bodies on the experiment group that the electrophoretic velocity is faster more than control and free group.Conclusion:The magnetic field in animal's body can raise the negative electric charges on the surface of erythrocyte to improve the microcirculation, this is the biological effect of magnetic field.

  20. Biological effects of electric fields: an overview

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, L.E.; Phillips, R.D.

    1983-11-01

    An overview of the literature suggests tha electric-field exposure is an environmental agent/influence of relatively low potential toxicity to biological systems. Generally, many of the biological effects which have been reported are quite subtle and differences between exposed and unexposed subjects may be masked by normal biological variations. However, several recent reports indicate possibly more serious consequences from chronic exposure, emphasizing the need for more research in epidemiology and laboratory experiments. This paper presents a cursory overview of investigations on the biological consequences of exposure to ELF electromagnetic fields. Three important topics are discussed, including: 1) the general methodology of exposure experiments, including those elements which are critical for definitive studies in biological systems; 2) a brief discussion of epidemiological and clinical studies conducted to date; and 3) a somewhat more extensive examination of animal experiments representing major areas of investigation (behavior, biological rhythms, nervous and endocrine systems, bone growth and repair, cardiovascular system and blood chemistry, immunology, reproduction, growth and development mortality and pathology, cellular and membrane studies, and mutagenesis). A discussion of current concepts, possible mechanisms and future directions of research is presented. 110 references.

  1. Biological effectiveness of neutrons: Research needs

    Energy Technology Data Exchange (ETDEWEB)

    Casarett, G.W.; Braby, L.A.; Broerse, J.J.; Elkind, M.M.; Goodhead, D.T.; Oleinick, N.L.

    1994-02-01

    The goal of this report was to provide a conceptual plan for a research program that would provide a basis for determining more precisely the biological effectiveness of neutron radiation with emphasis on endpoints relevant to the protection of human health. This report presents the findings of the experts for seven particular categories of scientific information on neutron biological effectiveness. Chapter 2 examines the radiobiological mechanisms underlying the assumptions used to estimate human risk from neutrons and other radiations. Chapter 3 discusses the qualitative and quantitative models used to organize and evaluate experimental observations and to provide extrapolations where direct observations cannot be made. Chapter 4 discusses the physical principles governing the interaction of radiation with biological systems and the importance of accurate dosimetry in evaluating radiation risk and reducing the uncertainty in the biological data. Chapter 5 deals with the chemical and molecular changes underlying cellular responses and the LET dependence of these changes. Chapter 6, in turn, discusses those cellular and genetic changes which lead to mutation or neoplastic transformation. Chapters 7 and 8 examine deterministic and stochastic effects, respectively, and the data required for the prediction of such effects at different organizational levels and for the extrapolation from experimental results in animals to risks for man. Gaps and uncertainties in this data are examined relative to data required for establishing radiation protection standards for neutrons and procedures for the effective and safe use of neutron and other high-LET radiation therapy.

  2. Investigation of protein-styrene oxide adducts as a molecularbiomarker of human exposed to styrene

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Hemoglobin-styrene oxide adducts in blood has been studied as a molecular biomarker of worker exposed to styrene.Determination of protein-styrene oxide adducts in different biological samples with modified Raney-Ni procedure is described in this paper. The following biological samples have been investigated: fresh rat blood reacted with styrene oxide in vitro; rat blood reacted with styrene or styrene oxide in vivo; vein blood from workers exposed to styrene in two factories. The data showed that there was a good linear dose-response relationship between reacting dose of styrene oxide or styrene and amount of protein-styrene oxide adducts in both in vitro and in vivo experiments. For human samples, a dose-response relationship between protein adducts and styrene exposure can be found in glass fiber factory, but not in piano manufacture plant.

  3. DNA adducts-chemical addons

    Directory of Open Access Journals (Sweden)

    T R Rajalakshmi

    2015-01-01

    Full Text Available DNA adduct is a piece of DNA covalently bond to a chemical (safrole, benzopyrenediol epoxide, acetaldehyde. This process could be the start of a cancerous cell. When a chemical binds to DNA, it gets damaged resulting in abnormal replication. This could be the start of a mutation and without proper DNA repair, this can lead to cancer. It is this chemical that binds with the DNA is our prime area of concern. Instead of performing the whole body analysis for diagnosing cancer, this test could be carried out for early detection of cancer. When scanning tunneling microscope is used, the DNA results can be obtained earlier. DNA adducts in scientific experiments are used as biomarkers.

  4. DNA adducts-chemical addons

    Science.gov (United States)

    Rajalakshmi, T. R.; AravindhaBabu, N.; Shanmugam, K. T.; Masthan, K. M. K.

    2015-01-01

    DNA adduct is a piece of DNA covalently bond to a chemical (safrole, benzopyrenediol epoxide, acetaldehyde). This process could be the start of a cancerous cell. When a chemical binds to DNA, it gets damaged resulting in abnormal replication. This could be the start of a mutation and without proper DNA repair, this can lead to cancer. It is this chemical that binds with the DNA is our prime area of concern. Instead of performing the whole body analysis for diagnosing cancer, this test could be carried out for early detection of cancer. When scanning tunneling microscope is used, the DNA results can be obtained earlier. DNA adducts in scientific experiments are used as biomarkers. PMID:26015708

  5. II. Biological studies of radiation effects

    Energy Technology Data Exchange (ETDEWEB)

    Lawrence, J.H.

    1948-05-24

    With the completion of the 184 inch cyclotron in Berkeley and the successful construction of a deflector system, it was possible to bring the 190 Mev deuteron and the 380 Mev alpha beams out into the air and to begin a study of the effects of high-energy deuteron beams by direct irradiation of biological specimens. The direct biological use of deuteron beams was attempted earlier in Berkeley by Marshak, MacLeish, and Walker in 1940. These and other investigators have been aware for some time of the potential usefulness of high energy particle beams for radio-biological studies and their suitability for biological investigations. R.R. Wilson advanced the idea of using fast proton beams to deliver radiation and intervening tissues. R.E. Zirkle pointed out that such particle beams may be focused or screened until a cross-section of the beam is small enough to study effects of irradiation under the microscope on single cells or on parts of single cells. This article gives an overview of the radiological use of high energy deuteron beams, including the following topics: potential uses of high energy particle beams; experiments on the physical properties of the beam; lethal effect of the deuteron beam on mice.

  6. [Biological effects of electromagnetic fields (author's transl)].

    Science.gov (United States)

    Bernhardt, J

    1979-08-01

    This résumé deals with thermal and nonthermal effects of electromagnetic fields on man. In consideration of two aspects a limitation is necessary. Firstly, there will be discussed only direct and immediate influences on biological cells and tissues, secondly, the treatment is limited to such phenomena, for which biophysical aproximations, based on experimental data, could be developed. Hazards for the human being may occur only by thermal effects within the microwave range. Regarding frequencies below approximately 30 kHz, excitation processes cannot be excluded in exceptional cases. Thermal effects are predominant, between 30 kHz and 100 kHz, before excitations can appear. Furthermore, by comparing the electrically and magnetically induced currents with the naturally flowing currents in man caused by the brain's and heart's electrical activity, a "lower boundaryline" was estimated. Regarding electric or magnetic field strengths undercutting this boundary-line, direct effects on the central nervous system may be excluded; other mechanisms should be responsible for demonstrated biological effects. The paper closes referring to some reports--presently discussed--on experimental findings of biological effects, which are observed as a result of the influence of electromagnetic fields of small field strengths.

  7. The Biological Effects of Bilirubin Photoisomers.

    Science.gov (United States)

    Jasprova, Jana; Dal Ben, Matteo; Vianello, Eleonora; Goncharova, Iryna; Urbanova, Marie; Vyroubalova, Karolina; Gazzin, Silvia; Tiribelli, Claudio; Sticha, Martin; Cerna, Marcela; Vitek, Libor

    2016-01-01

    Although phototherapy was introduced as early as 1950's, the potential biological effects of bilirubin photoisomers (PI) generated during phototherapy remain unclear. The aim of our study was to isolate bilirubin PI in their pure forms and to assess their biological effects in vitro. The three major bilirubin PI (ZE- and EZ-bilirubin and Z-lumirubin) were prepared by photo-irradiation of unconjugated bilirubin. The individual photoproducts were chromatographically separated (TLC, HPLC), and their identities verified by mass spectrometry. The role of Z-lumirubin (the principle bilirubin PI) on the dissociation of bilirubin from albumin was tested by several methods: peroxidase, fluorescence quenching, and circular dichroism. The biological effects of major bilirubin PI (cell viability, expression of selected genes, cell cycle progression) were tested on the SH-SY5Y human neuroblastoma cell line. Lumirubin was found to have a binding site on human serum albumin, in the subdomain IB (or at a close distance to it); and thus, different from that of bilirubin. Its binding constant to albumin was much lower when compared with bilirubin, and lumirubin did not affect the level of unbound bilirubin (Bf). Compared to unconjugated bilirubin, bilirubin PI did not have any effect on either SH-SY5Y cell viability, the expression of genes involved in bilirubin metabolism or cell cycle progression, nor in modulation of the cell cycle phase. The principle bilirubin PI do not interfere with bilirubin albumin binding, and do not exert any toxic effect on human neuroblastoma cells.

  8. The effect of knockout of sulfotransferases 1a1 and 1d1 and of transgenic human sulfotransferases 1A1/1A2 on the formation of DNA adducts from furfuryl alcohol in mouse models.

    Science.gov (United States)

    Sachse, Benjamin; Meinl, Walter; Glatt, Hansruedi; Monien, Bernhard H

    2014-10-01

    Furfuryl alcohol is a rodent carcinogen present in numerous foodstuffs. Sulfotransferases (SULTs) convert furfuryl alcohol into the DNA reactive and mutagenic 2-sulfoxymethylfuran. Sensitive techniques for the isotope-dilution ultra performance liquid chromatography-tandem mass spectrometry quantification of resulting DNA adducts, e.g. N (2)-((furan-2-yl)methyl)-2'-deoxyguanosine (N (2)-MF-dG), were developed. To better understand the contribution of specific SULT forms to the genotoxicity of furfuryl alcohol in vivo, we studied the tissue distribution of N (2)-MF-dG in different mouse models. Earlier mutagenicity studies with Salmonella typhimurium strains expressing different human and murine SULT forms indicated that human SULT1A1 and murine Sult1a1 and 1d1 catalyze furfuryl alcohol sulfo conjugation most effectively. Here, we used three mouse lines to study the bioactivation of furfuryl alcohol by murine SULTs, FVB/N wild-type (wt) mice and two genetically modified models lacking either murine Sult1a1 or Sult1d1. The animals received a single dose of furfuryl alcohol, and the levels of the DNA adducts were determined in liver, kidney, lung, colon and small intestine. The effect of Sult1d1 gene disruption on the genotoxicity of furfuryl alcohol was moderate and limited to kidney and small intestine. In contrast, the absence of functional Sult1a1 had a massive influence on the adduct levels, which were lowered by 33-73% in all tissues of the female Sult1a1 null mice compared with the wt animals. The detection of high N (2)-MF-dG levels in a humanized mouse line expressing hSULT1A1/1A2 instead of endogeneous Sult1a1 and Sult1d1 supports the hypothesis that furfuryl alcohol is converted to the mutagenic 2-sulfoxymethylfuran also in humans.

  9. Mechanistic Effects of Calcitriol in Cancer Biology

    Directory of Open Access Journals (Sweden)

    Lorenza Díaz

    2015-06-01

    Full Text Available Besides its classical biological effects on calcium and phosphorus homeostasis, calcitriol, the active vitamin D metabolite, has a broad variety of actions including anticancer effects that are mediated either transcriptionally and/or via non-genomic pathways. In the context of cancer, calcitriol regulates the cell cycle, induces apoptosis, promotes cell differentiation and acts as anti-inflammatory factor within the tumor microenvironment. In this review, we address the different mechanisms of action involved in the antineoplastic effects of calcitriol.

  10. Sodium adduct formation efficiency in ESI source.

    Science.gov (United States)

    Kruve, Anneli; Kaupmees, Karl; Liigand, Jaanus; Oss, Merit; Leito, Ivo

    2013-06-01

    Formation of sodium adducts in electrospray (ESI) has been known for long time, but has not been used extensively in practice, and several important aspects of Na(+) adduct formation in ESI source have been almost unexplored: the ionization efficiency of different molecules via Na(+) adduct formation, its dependence on molecular structure and Na(+) ion concentration in solution, fragmentation behaviour of the adducts as well as the ruggedness (a prerequisite for wider practical use) of ionization via Na(+) adduct formation. In this work, we have developed a parameter describing sodium adducts formation efficiency (SAFE) of neutral molecules and have built a SAFE scale that ranges for over four orders of magnitude and contains 19 compounds. In general, oxygen bases have higher efficiency of Na(+) adducts formation than nitrogen bases because of the higher partial negative charge on oxygen atoms and competition from protonation in the case of nitrogen bases. Chelating ability strongly increases the Na(+) adduct formation efficiency. We show that not only protonation but also Na(+) adduct formation is a quantitative and reproducible process if relative measurements are performed.

  11. Biological effects of polycyclic aromatic hydrocarbons (PAH) and their first metabolic products in in vivo exposed Atlantic cod (Gadus morhua).

    Science.gov (United States)

    Pampanin, Daniela M; Le Goff, Jeremie; Skogland, Karianne; Marcucci, Cristian R; Øysæd, Kjell Birger; Lorentzen, Marianne; Jørgensen, Kåre B; Sydnes, Magne O

    2016-01-01

    The monitoring of the presence of polycyclic aromatic hydrocarbons (PAH) in the aquatic environment is a worldwide activity since some of these compounds are well-established carcinogens and mutagens. Contaminants in this class are in fact regarded as priority hazardous substances for environmental pollution (Water Framework Directive 2000/60/EC). In this study, Atlantic cod (Gadus morhua) was selected to assess in vivo effects of two PAH and their first metabolic products, namely, the corresponding trans-dihydrodiols, using biological markers. Fish were exposed for 1 wk to a single PAH (naphthalene or chrysene) and its synthetic metabolites ((1R,2R)-1,2-dihydronaphthalene-1,2-diol and (1R,2R)-1,2-dihydrochrysene-1,2-diol) by intraperitoneal injection in a continuous seawater flow system. After exposure, PAH metabolism including PAH metabolites in bile and ethoxyresorufin O-deethylase (EROD) activity, oxidative stress glutathione S-transferases (GST) and catalase (CAT) activities, and genotoxicity such as DNA adducts were evaluated, as well as general health conditions including condition index (CI), hepatosomatic index (HSI), and gonadosomatic index (GSI). PAH metabolite values were low and not significantly different when measured with the fixed-wavelength fluorescence screening method, while the gas chromatography-mass spectroscopy (GC-MS) method showed an apparent dose response in fish exposed to naphthalene. DNA adduct levels ≥0.16 × 10(-8) relative adduct level (RAL) were detected. It should be noted that 0.16 × 10(-8) RAL is considered the maximal acceptable background level for this species. The other biomarkers activities of catalase, GST, and EROD did not display a particular compound- or dose-related response. The GSI values were significantly lower in some chrysene- and in both naphthalene- and naphthalene diol-exposed groups compared to control.

  12. Urinary physiologic and chemical metabolic effects on the urothelial cytotoxicity and potential DNA adducts of o-phenylphenol in male rats.

    Science.gov (United States)

    Smith, R A; Christenson, W R; Bartels, M J; Arnold, L L; St John, M K; Cano, M; Garland, E M; Lake, S G; Wahle, B S; McNett, D A; Cohen, S M

    1998-06-01

    ortho-Phenylphenol (OPP), a fungicide and antibacterial agent with food residues, is carcinogenic to rat bladder. The present studies provide information on changes in urinary composition and urinary metabolites, urothelial cytotoxicity and regenerative hyperplasia, and DNA adducts in male F344 rats fed OPP. An initial experiment evaluated dietary doses of 0, 1,000, 4,000, and 12,500 ppm OPP fed for 13 weeks. There was no evidence of urinary calculi, microcrystalluria, or calcium phosphate-containing precipitate, but urothelial cytotoxicity and hyperplasia occurred at the highest dose only. In a second experiment, rats were fed dietary OPP levels of 0, 800, 4,000, 8,000, and 12,500 ppm. Urinary pH was > 7 in all groups. Urinary volume was increased at the 2 highest doses with consequent decreases in osmolality, creatinine, and other solutes. Total urinary OPP metabolite excretions were increased, mostly excreted as conjugates of OPP and of phenylhydroquinone. Free OPP or free metabolites accounted for less than 2% excreted in the urine without a dose response. Urothelial toxicity and hyperplasia occurred only at doses of 8,000 and 12,500 ppm. OPP-DNA adducts were not detected in the urothelium at any dose. In summary, OPP produces cytotoxicity and proliferation of the urothelium at dietary doses > or = 8,000 ppm without formation of urinary solids. The paucity of unconjugated metabolites and the lack of OPP-DNA adducts suggests that OPP is acting as a bladder carcinogen in male rats by inducing cytotoxicity and hyperplasia without it or its metabolites directly binding to DNA.

  13. Quantitation of DNA Adducts Induced by 1,3-Butadiene

    Science.gov (United States)

    Sangaraju, Dewakar; Villalta, Peter W.; Wickramaratne, Susith; Swenberg, James; Tretyakova, Natalia

    2014-07-01

    Human exposure to 1,3-butadiene (BD) present in automobile exhaust, cigarette smoke, and forest fires is of great concern because of its potent carcinogenicity. The adverse health effects of BD are mediated by its epoxide metabolites such as 3,4-epoxy-1-butene (EB), which covalently modify genomic DNA to form promutagenic nucleobase adducts. Because of their direct role in cancer, BD-DNA adducts can be used as mechanism-based biomarkers of BD exposure. In the present work, a mass spectrometry-based methodology was developed for accurate, sensitive, and precise quantification of EB-induced N-7-(1-hydroxy-3-buten-2-yl) guanine (EB-GII) DNA adducts in vivo. In our approach, EB-GII adducts are selectively released from DNA backbone by neutral thermal hydrolysis, followed by ultrafiltration, offline HPLC purification, and isotope dilution nanoLC/ESI+-HRMS3 analysis on an Orbitrap Velos mass spectrometer. Following method validation, EB-GII lesions were quantified in human fibrosarcoma (HT1080) cells treated with micromolar concentrations of EB and in liver tissues of rats exposed to sub-ppm concentrations of BD (0.5-1.5 ppm). EB-GII concentrations increased linearly from 1.15 ± 0.23 to 10.11 ± 0.45 adducts per 106 nucleotides in HT1080 cells treated with 0.5-10 μM DEB. EB-GII concentrations in DNA of laboratory rats exposed to 0.5, 1.0, and 1.5 ppm BD were 0.17 ± 0.05, 0.33 ± 0.08, and 0.50 ± 0.04 adducts per 106 nucleotides, respectively. We also used the new method to determine the in vivo half-life of EB-GII adducts in rat liver DNA (2.20 ± 0.12 d) and to detect EB-GII in human blood DNA. To our knowledge, this is the first application of nanoLC/ESI+-HRMS3 Orbitrap methodology to quantitative analysis of DNA adducts in vivo.

  14. Spin traps: in vitro toxicity and stability of radical adducts.

    Science.gov (United States)

    Khan, Nadeem; Wilmot, Carmen M; Rosen, Gerald M; Demidenko, Eugene; Sun, Jie; Joseph, Joy; O'Hara, Julia; Kalyanaraman, B; Swartz, Harold M

    2003-06-01

    We have evaluated the effects of DMPO, CMPO, EMPO, BMPO, and DEPMPO on functioning CHO cells and the stability of the radical adducts in the presence of cells. The potential toxic effects of the spin traps were measured by two estimates of cell viability (trypan blue exclusion and colony formation) and one of cell function (rate of oxygen consumption). We also studied the effects of the spin traps on colony formation in a second cell line, 9L tumor cells. Toxicity varied with the type of cell line and the parameter that was measured. In aqueous solutions the order of stability for all spin adducts was SO(3) > OH > CH(3), while in cell suspensions it was SO(3) > OH approximately CH(3). The radical adducts of the new spin traps have significantly increased stability as compared to DMPO. These results indicate that the new spin traps potentially offer increased stability of spin adducts in functioning cells. It also is clear that it is necessary to carry out appropriate studies of the stability and toxicity in the system that is to be studied for any particular use of these spin traps. It then should be feasible to select the spin trap(s) best suited for the proposed study.

  15. Bulky DNA adducts in white blood cells: a pooled analysis of 3,600 subjects

    DEFF Research Database (Denmark)

    Ricceri, Fulvio; Godschalk, Roger W; Peluso, Marco;

    2010-01-01

    Bulky DNA adducts are markers of exposure to genotoxic aromatic compounds, which reflect the ability of an individual to metabolically activate carcinogens and to repair DNA damage. Polycyclic aromatic hydrocarbons (PAHs) represent a major class of carcinogens that are capable of forming such add......Bulky DNA adducts are markers of exposure to genotoxic aromatic compounds, which reflect the ability of an individual to metabolically activate carcinogens and to repair DNA damage. Polycyclic aromatic hydrocarbons (PAHs) represent a major class of carcinogens that are capable of forming...... such adducts. Factors that have been reported to be related to DNA adduct levels include smoking, diet, body mass index (BMI), genetic polymorphisms, the season of collection of biologic material, and air pollutants....

  16. The Biological Effects of Bilirubin Photoisomers.

    Directory of Open Access Journals (Sweden)

    Jana Jasprova

    Full Text Available Although phototherapy was introduced as early as 1950's, the potential biological effects of bilirubin photoisomers (PI generated during phototherapy remain unclear. The aim of our study was to isolate bilirubin PI in their pure forms and to assess their biological effects in vitro. The three major bilirubin PI (ZE- and EZ-bilirubin and Z-lumirubin were prepared by photo-irradiation of unconjugated bilirubin. The individual photoproducts were chromatographically separated (TLC, HPLC, and their identities verified by mass spectrometry. The role of Z-lumirubin (the principle bilirubin PI on the dissociation of bilirubin from albumin was tested by several methods: peroxidase, fluorescence quenching, and circular dichroism. The biological effects of major bilirubin PI (cell viability, expression of selected genes, cell cycle progression were tested on the SH-SY5Y human neuroblastoma cell line. Lumirubin was found to have a binding site on human serum albumin, in the subdomain IB (or at a close distance to it; and thus, different from that of bilirubin. Its binding constant to albumin was much lower when compared with bilirubin, and lumirubin did not affect the level of unbound bilirubin (Bf. Compared to unconjugated bilirubin, bilirubin PI did not have any effect on either SH-SY5Y cell viability, the expression of genes involved in bilirubin metabolism or cell cycle progression, nor in modulation of the cell cycle phase. The principle bilirubin PI do not interfere with bilirubin albumin binding, and do not exert any toxic effect on human neuroblastoma cells.

  17. Method for photo-altering a biological system to improve biological effect

    Science.gov (United States)

    Hill, Richard A.; Doiron, Daniel R.; Crean, David H.

    2000-08-01

    Photodynamic therapy is a new adjunctive therapy for filtration surgery that does not use chemotherapy agents or radiation, but uses pharmacologically-active sensitizing compounds to produce a titratable, localized, transient, post operative avascular conjunctiva. A photosensitizing agent in a biological system is selectively activated by delivering the photosensitive agent to the biological system and laser activating only a spatially selected portion of the delivered photosensitive agent. The activated portion of the photosensitive agent reacts with the biological system to obtain a predetermined biological effect. As a result, an improved spatial disposition and effectuation of the biological effect by the photosensitive agent in the biological system is achieved.

  18. Crystal structure of the 1,3,6,8-tetraazatricyclo[4.3.1.13,8]undecane (TATU–4-nitrophenol (1/2 adduct: the role of anomeric effect in the formation of a second hydrogen-bond interaction

    Directory of Open Access Journals (Sweden)

    Augusto Rivera

    2015-11-01

    Full Text Available In the title ternary co-crystalline adduct, C7H14N4·2C6H5NO3, molecules are linked by two intermolecular O—H...N hydrogen bonds, forming a tricomponent aggregates in the asymmetric unit. The hydrogen-bond formation to one of the N atoms is enough to induce structural stereoelectronic effects in the normal donor→acceptor direction. In the title adduct, the two independent nitrophenol molecules are essentially planar, with maximum deviations of 0.0157 (13 and 0.0039 (13 Å. The dihedral angles between the planes of the nitro group and the attached benzene rings are 4.04 (17 and 5.79 (17°. In the crystal, aggregates are connected by C—H...O hydrogen bonds, forming a supramolecular dimer enclosing an R66(32 ring motif. Additional C—H...O intermolecular hydrogen-bonding interactions form a second supramolecular inversion dimer with an R22(10 motif. These units are linked via C—H...O and C—H...N hydrogen bonds, forming a three-dimensional network.

  19. Isoflavones: estrogenic activity, biological effect and bioavailability.

    Science.gov (United States)

    Vitale, Daniela Cristina; Piazza, Cateno; Melilli, Barbara; Drago, Filippo; Salomone, Salvatore

    2013-03-01

    Isoflavones are phytoestrogens with potent estrogenic activity; genistein, daidzein and glycitein are the most active isoflavones found in soy beans. Phytoestrogens have similarity in structure with the human female hormone 17-β-estradiol, which can bind to both alpha and beta estrogen receptors, and mimic the action of estrogens on target organs, thereby exerting many health benefits when used in some hormone-dependent diseases. Numerous clinical studies claim benefits of genistein and daidzein in chemoprevention of breast and prostate cancer, cardiovascular disease and osteoporosis as well as in relieving postmenopausal symptoms. The ability of isoflavones to prevent cancer and other chronic diseases largely depends on pharmacokinetic properties of these compounds, in particular absorption and distribution to the target tissue. The chemical form in which isoflavones occur is important because it influences their bioavailability and, therefore, their biological activity. Glucose-conjugated isoflavones are highly polar, water-soluble compounds. They are hardly absorbed by the intestinal epithelium and have weaker biological activities than the corresponding aglycone. Different microbial families of colon can transform glycosylated isoflavones into aglycones. Clinical studies show important differences between the aglycone and conjugated forms of genistein and daidzein. The evaluation of isoflavone metabolism and bioavailability is crucial to understanding their biological effects. Lipid-based formulations such as drug incorporation into oils, emulsions and self-microemulsifying formulations have been introduced to increase bioavailability. Complexation with cyclodextrin also represent a valid method to improve the physicochemical characteristics of these substances in order to be absorbed and distributed to target tissues. We review and discuss pharmacokinetic issues that critically influence the biological activity of isoflavones.

  20. Theoretical study of the hydroxyl radical addition to uracil and photochemistry of the formed U6OH• adduct.

    Science.gov (United States)

    Francés-Monerris, Antonio; Merchán, Manuela; Roca-Sanjuán, Daniel

    2014-03-20

    Hydroxyl radical ((•)OH) is produced in biological systems by external or endogenous agents. It can damage DNA/RNA by attacking pyrimidine nucleobases through the addition to the C5═C6 double bond. The adduct resulting from the attachment at the C5 position prevails in the experimental measurements, although the reasons for this preference remain unclear. The first aim of this work is therefore to shed light on the comprehension of this important process. Thus, the thermal (•)OH addition to the C5═C6 double bond of uracil has been studied theoretically by using DFT, MP2, and the multiconfigurational CASPT2//CASSCF methodologies. The in-vacuo results obtained with the latter protocol plus the analysis of solvent effects support the experimental observation. A significant lower barrier height is predicted for the C5 pathway with respect to that of the C6 route. In contrast to the C5 adduct, the C6 adduct is able to absorb visible light. Hence, the second aim of the work is to study the photochemistry of this species using the CASPT2//CASSCF methodology within the framework of the photochemical reaction path approach (PRPA). The nonradiative decay to the ground state of this compound has been characterized. A photoreactive character is predicted for the C6 adduct in the excited states according to the presence of excited-state minima along the main decay channel. Finally, a new mechanism of photodissociation has been explored, which implies the photoinduced regeneration of the canonical nucleobase by irradiating with visible light, being therefore relevant in RNA protection against damage by reactive oxygen species.

  1. BIOLOGICAL EFFECTS ON THE SOURCE OF GEONEUTRINOS

    DEFF Research Database (Denmark)

    Sleep, Norman H.; Bird, Dennis K.; Rosing, Minik T.

    2013-01-01

    Detection of antineutrinos from U and Th series decay within the Earth (geoneutrinos) constrains the absolute abundance of these elements. Marine detectors will measure the ratio over the mantle beneath the site and provide spatial averaging. The measured mantle Th/U may well be significantly below...... its bulk earth value of similar to 4; Pb isotope measurements on mantle-derived rocks yield low Th/U values, effectively averaged over geological time. The physics of the modern biological process is complicated, but the net effect is that much of the U in the mantle comes from subducted marine......, these elements behave similarly in the absence of life, where the elements occur as U(IV) and Th(IV), which do not significantly fractionate during igneous processes. Neither do they fractionate during weathering, as they are essentially insoluble in water in surface environments. Th(IV) and U(IV) remain...

  2. Aminoguanidine pyridoxal adduct is superior to aminoguanidine for preventing diabetic nephropathy in mice.

    Science.gov (United States)

    Miyoshi, H; Taguchi, T; Sugiura, M; Takeuchi, M; Yanagisawa, K; Watanabe, Y; Miwa, I; Makita, Z; Koike, T

    2002-07-01

    Aminoguanidine inhibits the formation of advanced glycation end-products, and has been extensively examined in animals. However, administration of aminoguanidine decreases the hepatic content of pyridoxal phosphate. In order to avoid this problem, we developed an aminoguanidine pyridoxal Schiff base adduct and examined its efficacy in vitro as well as in a model of diabetic nephropathy. Mice with streptozotocin-induced diabetes were treated with aminoguanidine or aminoguanidine pyridoxal adduct for 9 weeks. An in vitro study was also performed to assess the antioxidant activity of aminoguanidine and its pyridoxal adduct. Neither drug altered glycemic control. Aminoguanidine pyridoxal adduct significantly improved urinary albumin excretion by 78.1 % compared with the diabetic control, and also had a better preventive effect on the progression of renal pathology than aminoguanidine did. Inhibition of glycation by both drugs was similar, but the antioxidant activity of the pyridoxal adduct was far superior. These findings suggest that aminoguanidine pyridoxal adduct may be superior to aminoguanidine, as it not only prevents vitamin B6 deficiency but is also better at controlling diabetic nephropathy, as this adduct inhibits oxidation as well as glycation.

  3. Biophysical aspects of lysozyme adduct with monocrotophos.

    Science.gov (United States)

    Amaraneni, Sreenivasa Rao; Kumar, Sudhir; Gourinath, Samudrala

    2014-09-01

    The present study on in vitro formation and characterization of lysozyme adduct with monocrotophos (MP) evaluates the potential of lysozyme to be used as a sensitive biomarker to monitor exposure levels to the commonly used organophosphorus pesticide monocrotophos. Crystallization of lysozyme protein adduct with monocrotophos was also undertaken to understand the adduct formation mechanism at a molecular level. The binding of organophosphorus pesticides to lysozyme is one of the key steps in their mutagenicity. The formation and structural characterization of lysozyme adduct with monocrotophos was done using MALDI-TOFMS, fluorescence, UV/Vis spectroscopy, circular dichroism, and X-ray diffraction studies. We report the crystal structure of lysozyme adduct with monocrotophos at 1.9 Å. It crystallized in the P43 space group with two monomers in one asymmetric unit having one molecule of monocrotophos bound to each protein chain. The results proved that the fluorescence quenching of lysozyme by monocrotophos is due to binding of monocrotophos with a tryptophan residue of lysozyme. Monocrotophos interacts most strongly with the Trp-108 and Asp-52 of lysozyme. The interactions of the monocrotophos molecule with the lysozyme suggest the formation of a stable adduct. In addition, the alteration of lysozyme secondary structure in the presence of monocrotophos was confirmed by circular dichroism and fluorescence inhibition of lysozyme by increasing monocrotophos and UV/Vis spectrophotometry. The formation of lysozyme adduct with monocrotophos was confirmed by MALDI-TOFMS.

  4. Biological effects of space radiation and development of effective countermeasures

    Science.gov (United States)

    Kennedy, Ann R.

    2014-04-01

    As part of a program to assess the adverse biological effects expected from astronauts' exposure to space radiation, numerous different biological effects relating to astronauts' health have been evaluated. There has been major focus recently on the assessment of risks related to exposure to solar particle event (SPE) radiation. The effects related to various types of space radiation exposure that have been evaluated are: gene expression changes (primarily associated with programmed cell death and extracellular matrix (ECM) remodeling), oxidative stress, gastrointestinal tract bacterial translocation and immune system activation, peripheral hematopoietic cell counts, emesis, blood coagulation, skin, behavior/fatigue (including social exploration, submaximal exercise treadmill and spontaneous locomotor activity), heart functions, alterations in biological endpoints related to astronauts' vision problems (lumbar puncture/intracranial pressure, ocular ultrasound and histopathology studies), and survival, as well as long-term effects such as cancer and cataract development. A number of different countermeasures have been identified that can potentially mitigate or prevent the adverse biological effects resulting from exposure to space radiation.

  5. Screening for DNA Alkylation Mono and Cross-Linked Adducts with a Comprehensive LC-MS(3) Adductomic Approach.

    Science.gov (United States)

    Stornetta, Alessia; Villalta, Peter W; Hecht, Stephen S; Sturla, Shana J; Balbo, Silvia

    2015-12-01

    A high-resolution/accurate-mass DNA adductomic approach was developed to investigate anticipated and unknown DNA adducts induced by DNA alkylating agents in biological samples. Two new features were added to a previously developed approach to significantly broaden its scope, versatility, and selectivity. First, the neutral loss of a base (guanine, adenine, thymine, or cytosine) was added to the original methodology's neutral loss of the 2'-deoxyribose moiety to allow for the detection of all DNA base adducts. Second, targeted detection of anticipated DNA adducts based on the reactivity of the DNA alkylating agent was demonstrated by inclusion of an ion mass list for data dependent triggering of MS(2) fragmentation events and subsequent MS(3) fragmentation. Additionally, untargeted screening of the samples, based on triggering of an MS(2) fragmentation event for the most intense ions of the full scan, was included for detecting unknown DNA adducts. The approach was tested by screening for DNA mono and cross-linked adducts in purified DNA and in DNA extracted from cells treated with PR104A, an experimental DNA alkylating nitrogen mustard prodrug currently under investigation for the treatment of leukemia. The results revealed the ability of this new DNA adductomic approach to detect anticipated and unknown PR104A-induced mono and cross-linked DNA adducts in biological samples. This methodology is expected to be a powerful tool for screening for DNA adducts induced by endogenous or exogenous exposures.

  6. Metabolic stability of superoxide adducts derived from newly developed cyclic nitrone spin traps.

    Science.gov (United States)

    Bézière, Nicolas; Hardy, Micael; Poulhès, Florent; Karoui, Hakim; Tordo, Paul; Ouari, Olivier; Frapart, Yves-Michel; Rockenbauer, Antal; Boucher, Jean-Luc; Mansuy, Daniel; Peyrot, Fabienne

    2014-02-01

    Reactive oxygen species are by-products of aerobic metabolism involved in the onset and evolution of various pathological conditions. Among them, the superoxide radical is of special interest as the origin of several damaging species such as H2O2, hydroxyl radical, or peroxynitrite (ONOO(-)). Spin trapping coupled with ESR is a method of choice to characterize these species in chemical and biological systems and the metabolic stability of the spin adducts derived from reaction of superoxide and hydroxyl radicals with nitrones is the main limit to the in vivo application of the method. Recently, new cyclic nitrones bearing a triphenylphosphonium or permethylated β-cyclodextrin moiety have been synthesized and their spin adducts demonstrated increased stability in buffer. In this article, we studied the stability of the superoxide adducts of four new cyclic nitrones in the presence of liver subcellular fractions and biologically relevant reductants using an original setup combining a stopped-flow device and an ESR spectrometer. The kinetics of disappearance of the spin adducts were analyzed using an appropriate simulation program. Our results highlight the interest of the new spin trapping agents CD-DEPMPO and CD-DIPPMPO for specific detection of superoxide with high stability of the superoxide adducts in the presence of liver microsomes.

  7. Cell Biology of Thiazide Bone Effects

    Science.gov (United States)

    Gamba, Gerardo; Riccardi, Daniela

    2008-09-01

    The thiazide-sensitive Na+:Cl- cotransporter (NCC) is the major pathway for salt reabsorption in the mammalian kidney. The activity of NCC is not only related to salt metabolism, but also to calcium and magnesium homeostasis due to the inverse relationship between NCC activity and calcium reabsorption. Hence, the thiazide-type diuretics that specifically block NCC have been used for years, not only for treatment of hypertension and edematous disease, but also for the management of renal stone disease. Epidemiological studies have shown that chronic thiazide treatment is associated with higher bone mineral density and reduced risk of bone fractures, which can only partly be explained in terms of their effects on the kidney. In this regard, we have recently shown that NCC is expressed in bone cells and that inhibition of NCC in bone, either by thiazides or by reduction of NCC protein with specific siRNA, is associated with increased mineralization in vitro. These observations open a field of study to begin to understand the cell biology of the beneficial effects of thiazides in bone.

  8. Detection of DNA adducts by bioluminescence

    Science.gov (United States)

    Xu, Shunqing; Tan, Xianglin; Yao, Qunfeng; He, Min; Zhou, Yikai; Chen, Jian

    2001-09-01

    Luminescent assay for detection ATP is very sensitive with limitation of 10-17 moles. ATP using styrene oxide as a model carcinogen we currently apply a luminescence technique to detect the very low levels of carcinogen-DNA adducts in vitro and in vivo. The bioluminescent assay of DNA adducts entails three consecutive steps: digestion of modified DNA to adducted dinucleoside monophosphate and normal nucleotide are hydrolyzed to nucleosides (N) by nuclease P1 and prostatic acid phosphomonesterase (PAP); incorporation of (gamma) -P of ATP into normal nucleoside(N); detection of consumption of ATP by luminescence. This assay does not require separate manipulation because of the selective property of nuclease P1. One fmol of carcinogen- DNA adducts was detected by luminescent assay. A good correlation between results of luminescent assay and 32P-postlabeling procedures has been observed. We detect 1 adduct in 108 nucleotides for 10(mu) g DNA sample. The procedures of luminescent method is very simple and low- cost. IT appears applicable to the ultra sensitive detection of low levels of DNA adducts without radioactive isotope.

  9. What Makes Biology Learning Difficult and Effective: Students' Views

    Science.gov (United States)

    Cimer, Atilla

    2012-01-01

    The present study aims to determine the biological topics that students have difficulties learning, the reasons why secondary school students have difficulties in learning biology, and ways to improve the effectiveness of students' biology learning. For these purposes, a self-administered questionnaire including three open-ended questions was…

  10. Biomarkers in natural fish populations indicate adverse biological effects of offshore oil production.

    Directory of Open Access Journals (Sweden)

    Lennart Balk

    Full Text Available BACKGROUND: Despite the growing awareness of the necessity of a sustainable development, the global economy continues to depend largely on the consumption of non-renewable energy resources. One such energy resource is fossil oil extracted from the seabed at offshore oil platforms. This type of oil production causes continuous environmental pollution from drilling waste, discharge of large amounts of produced water, and accidental spills. METHODS AND PRINCIPAL FINDINGS: Samples from natural populations of haddock (Melanogrammus aeglefinus and Atlantic cod (Gadus morhua in two North Sea areas with extensive oil production were investigated. Exposure to and uptake of polycyclic aromatic hydrocarbons (PAHs were demonstrated, and biomarker analyses revealed adverse biological effects, including induction of biotransformation enzymes, oxidative stress, altered fatty acid composition, and genotoxicity. Genotoxicity was reflected by a hepatic DNA adduct pattern typical for exposure to a mixture of PAHs. Control material was collected from a North Sea area without oil production and from remote Icelandic waters. The difference between the two control areas indicates significant background pollution in the North Sea. CONCLUSION: It is most remarkable to obtain biomarker responses in natural fish populations in the open sea that are similar to the biomarker responses in fish from highly polluted areas close to a point source. Risk assessment of various threats to the marine fish populations in the North Sea, such as overfishing, global warming, and eutrophication, should also take into account the ecologically relevant impact of offshore oil production.

  11. Glottal configuration, acoustic, and aerodynamic changes induced by variation in suture direction in arytenoid adduction procedures.

    Science.gov (United States)

    Inagi, Katsuhide; Connor, Nadine P; Suzuki, Tatsutoshi; Ford, Charles N; Bless, Diane M; Nakajima, Masami

    2002-10-01

    Arytenoid adduction is a phonosurgical procedure in which the arytenoid cartilages are approximated to reduce posterior glottal gap size and improve voice. Voice outcomes following arytenoid adduction are not always optimal. The goal of this study was to systematically vary suture direction and force of pull on the arytenoid cartilages in a human excised laryngeal model to determine the optimal combination of factors for reducing glottal gap and improving voice. Several factors demonstrated significant effects. Changes in suture direction and force of pull affected glottal configuration in both the horizontal and vertical planes. Increased force of pull on the muscular process resulted in increased adduction of the vocal process for all suture directions. Changes in suture direction and force of pull also affected acoustic and aerodynamic measures of induced voice. Therefore, voice outcomes can be optimized with arytenoid adduction if the vocal fold plane is accurately adjusted.

  12. Biologically based multistage modeling of radiation effects

    Energy Technology Data Exchange (ETDEWEB)

    William Hazelton; Suresh Moolgavkar; E. Georg Luebeck

    2005-08-30

    This past year we have made substantial progress in modeling the contribution of homeostatic regulation to low-dose radiation effects and carcinogenesis. We have worked to refine and apply our multistage carcinogenesis models to explicitly incorporate cell cycle states, simple and complex damage, checkpoint delay, slow and fast repair, differentiation, and apoptosis to study the effects of low-dose ionizing radiation in mouse intestinal crypts, as well as in other tissues. We have one paper accepted for publication in ''Advances in Space Research'', and another manuscript in preparation describing this work. I also wrote a chapter describing our combined cell-cycle and multistage carcinogenesis model that will be published in a book on stochastic carcinogenesis models edited by Wei-Yuan Tan. In addition, we organized and held a workshop on ''Biologically Based Modeling of Human Health Effects of Low dose Ionizing Radiation'', July 28-29, 2005 at Fred Hutchinson Cancer Research Center in Seattle, Washington. We had over 20 participants, including Mary Helen Barcellos-Hoff as keynote speaker, talks by most of the low-dose modelers in the DOE low-dose program, experimentalists including Les Redpath (and Mary Helen), Noelle Metting from DOE, and Tony Brooks. It appears that homeostatic regulation may be central to understanding low-dose radiation phenomena. The primary effects of ionizing radiation (IR) are cell killing, delayed cell cycling, and induction of mutations. However, homeostatic regulation causes cells that are killed or damaged by IR to eventually be replaced. Cells with an initiating mutation may have a replacement advantage, leading to clonal expansion of these initiated cells. Thus we have focused particularly on modeling effects that disturb homeostatic regulation as early steps in the carcinogenic process. There are two primary considerations that support our focus on homeostatic regulation. First, a number of

  13. Biological Effects on the Source of Geoneutrinos

    Science.gov (United States)

    Sleep, Norman H.; Bird, Dennis K.; Rosing, Minik T.

    2013-11-01

    Detection of antineutrinos from U and Th series decay within the Earth (geoneutrinos) constrains the absolute abundance of these elements. Marine detectors will measure the ratio over the mantle beneath the site and provide spatial averaging. The measured mantle Th/U may well be significantly below its bulk earth value of 4; Pb isotope measurements on mantle-derived rocks yield low Th/U values, effectively averaged over geological time. The physics of the modern biological process is complicated, but the net effect is that much of the U in the mantle comes from subducted marine sediments and subducted upper oceanic crust. That is, U subducts preferentially relative to Th. Oxygen ultimately from photosynthesis oxidizes U(IV) to U(VI), which is soluble during weathering and sediment transport. Dissolved U(VI) reacts with FeO in the oceanic crust and organic carbon within sediments to become immobile U(IV). These deep marine rocks are preferentially subducted relative to Th(IV)-bearing continental margin rocks. Ferric iron from anoxygenic photosynthesis and oxygen in local oases likely mobilized some U during the Archean Era when there was very little O2 in the air. Conversely, these elements behave similarly in the absence of life, where the elements occur as U(IV) and Th(IV), which do not significantly fractionate during igneous processes. Neither do they fractionate during weathering, as they are essentially insoluble in water in surface environments. Th(IV) and U(IV) remain in solid clay-sized material. Overall, geoneutrino data constrain the masses of mantle chemical and isotopic domains recognized by studies of mantle-derived rocks and show the extent of recycling into the mantle over geological time.

  14. SIX2 Effects on Wilms Tumor Biology

    Directory of Open Access Journals (Sweden)

    Janene Pierce

    2014-12-01

    Full Text Available Wilms tumor (WT blastema retains gene expression profiles characteristic of the multipotent nephron progenitor pool, or cap mesenchyme (CM, in the developing kidney. As a result, WT blastema and the CM are believed to represent contextual analogues of one another. Sine oculis homeobox 2 (SIX2 is a transcription factor expressed specifically in the CM, provides a critical mechanism for CM self-renewal, and remains persistently active in WT blastema, although its purpose in this childhood malignancy remains unclear. We hypothesized that SIX2, analogous to its function in development, confers a survival pathway to blastema, the putative WT stem cell. To test its functional significance in WT biology, wild-type SIX2 was overexpressed in the human WT cell line, WiT49. After validating this model, SIX2 effects on anchorage-independent growth, proliferation, invasiveness, canonical WNT pathway signaling, and gene expression of specific WNT pathway participants were evaluated. Relative to controls, WiT49 cells overexpressing SIX2 showed significantly enhanced anchorage-independent growth and early-passage proliferation representing surrogates of cell survival. Interestingly, overexpression of SIX2 generally repressed TCF/LEF-dependent canonical WNT signaling, which activates and coordinates both differentiation and stem pathways, but significantly heightened canonical WNT signaling through the survivin promoter, a mechanism that exclusively maintains the stem state. In summary, when overexpressed in a human WT cell line, SIX2 enhances cell survival and appears to shift the balance in WNT/β-catenin signaling away from a differentiation path and toward a stem cell survival path.

  15. The analysis of high explosives by liquid chromatography/electrospray ionization mass spectrometry: multiplexed detection of negative ion adducts.

    Science.gov (United States)

    Mathis, John A; McCord, Bruce R

    2005-01-01

    The negative ion electrospray ionization mass spectrometric (ESI-MS) detection of adducts of high explosives with chloride, formate, acetate, and nitrate was used to demonstrate the gas-phase interaction of neutral explosives with these anions. The relative intensities of the adduct species were determined to compare the competitive formation of the selected high explosives and anions. The relative stability of the adduct species varies, yielding preferential formation of certain anionic adducts with different high explosives. To exploit this effect, an isocratic high-performance liquid chromatography (HPLC)/ESI-MS method was developed and used for the simultaneous analysis of high explosives using two different techniques for the addition of the anionic additives; pre- and post-column. The results show that the pre-column approach provides similar results with improved selectivity for specific explosives. By detecting characteristic adduct species for each explosive, this method provides a qualitative and quantitative approach for the analysis and identification of high explosives.

  16. Tamoxifen-DNA adduct formation in monkey and human reproductive organs.

    Science.gov (United States)

    Hernandez-Ramon, Elena E; Sandoval, Nicole A; John, Kaarthik; Cline, J Mark; Wood, Charles E; Woodward, Ruth A; Poirier, Miriam C

    2014-05-01

    The estrogen analog tamoxifen (TAM), used for adjuvant therapy of breast cancer, induces endometrial and uterine tumors in breast cancer patients. Proliferation stimulus of the uterine endometrium is likely involved in tumor induction, but genotoxicity may also play a role. Formation of TAM-DNA adducts in human tissues has been reported but remains controversial. To address this issue, we examined TAM-DNA adducts in uteri from two species of monkeys, Erythrocebus patas (patas) and Macaca fascicularis (macaque), and in human endometrium and myometrium. Monkeys were given 3-4 months of chronic TAM dosing scaled to be equivalent to the daily human dose. In the uteri, livers and brains from the patas (n = 3), and endometrium from the macaques (n = 4), TAM-DNA adducts were measurable by TAM-DNA chemiluminescence immunoassay. Average TAM-DNA adduct values for the patas uteri (23 adducts/10(8) nucleotides) were similar to those found in endometrium of the macaques (19 adducts/10(8) nucleotides). Endometrium of macaques exposed to both TAM and low-dose estradiol (n = 5) averaged 34 adducts/10(8) nucleotides. To examine TAM-DNA persistence in the patas, females (n = 3) were exposed to TAM for 3 months and to no drug for an additional month, resulting in low or non-detectable TAM-DNA in livers and uteri. Human endometrial and myometrial samples from women receiving (n = 8) and not receiving (n = 8) TAM therapy were also evaluated. Women receiving TAM therapy averaged 10.3 TAM-DNA adducts/10(8) nucleotides, whereas unexposed women showed no detectable TAM-DNA. The data indicate that genotoxicity, in addition to estrogen agonist effects, may contribute to TAM-induced human endometrial cancer.

  17. In vitro studies of the genotoxic effects of bitumen and coal-tar fume condensates: comparison of data obtained by mutagenicity testing and DNA adduct analysis by 32P-postlabelling.

    Science.gov (United States)

    De Méo, M; Genevois, C; Brandt, H; Laget, M; Bartsch, H; Castegnaro, M

    1996-08-14

    Bitumens contain traces of polycyclic aromatic compounds (PACs), a part of which will end up in the fumes emitted during hot handling of bitumen-containing products, e.g. during roadpaving. Although exposure of workers to these fumes is low, it might lead to health problems. Studies on bitumen fume condensates (BFCs) showed weak to moderate mutagenic activities, but studies on DNA adduct formation have not been reported. Therefore, a study was initiated in which fumes were generated from two road grade bitumens, in such a way that they were representative of the fumes produced in the field. The combined vapour/particulates were tested in vitro for their ability to produce DNA adducts and in modified Ames mutation assays, using a number of different strains. An attempt was made to relate the results to chemical data, such as the content of a number of individual polycyclic aromatic hydrocarbons (PAHs) and with a measure for the total PAC content. As a reference material fume condensate from coal-tar (coal-tar pitch volatiles; CTPV) were subjected to the same tests. All fume condensates tested were mutagenic to all strains and induced the formation of DNA adducts. The patterns of DNA adducts, obtained by 32P-postlabelling, arising from the BFCs were qualitatively different from the patterns of adducts obtained from the CTPVs, implying qualitative differences in the nature of the compounds responsible for the formation of these adducts. This is corroborated by the observation that for BFCs quantitative adduct levels are higher than would be expected based on the PAH content. These data thus indicate that the PAHs analysed are not the sole components responsible for adduct formation from BFCs, but that an important contribution comes from other (hetero- and/or substituted-) PACs.

  18. N-acetylcysteine prevents the geldanamycin cytotoxicity by forming geldanamycin-N-acetylcysteine adduct.

    Science.gov (United States)

    Mlejnek, Petr; Dolezel, Petr

    2014-09-05

    Geldanamycin (GDN) is a benzoquinone ansamycin antibiotic with anti-proliferative activity on tumor cells. GDN cytotoxicity has been attributed to the disruption of heat shock protein 90 (Hsp90) binding and stabilizing client proteins, and by the induction of oxidative stress with concomitant glutathione (GSH) depletion. The later mechanism of cytotoxicity can be abrogated by N-acetylcysteine (NAC). It was suggested that NAC prevents GDN cytotoxicity mainly by the restoring of glutathione (GSH) level (Clark et al., 2009). Here we argue that NAC does not protect cells from the GDN cytotoxicity by restoring the level of GSH. A detailed LC/MS/MS analysis of cell extracts indicated formation of GDN adducts with GSH. The amount of the GDN-GSH adduct is proportional to the GDN concentration and increases with incubation time. While nanomolar and low micromolar GDN concentrations induce cell death without an apparent GSH decrease, only much higher micromolar GDN concentrations cause a significant GSH decrease. Therefore, only high micromolar GDN concentrations can cause cell death which might be related to GSH depletion. Addition of NAC leads to the formation of adducts with GDN which diminish formation of GDN adducts with GSH. NAC also forms stable adducts with GDN extracellularly. Although NAC induces an increase in the GSH pool, this effect is not crucial for abrogation of GDN cytotoxicity. Indeed, the presence of NAC in the growth medium causes a rapid conversion of GDN into the GDN-NAC adduct, which is the real cause of the abrogated GDN cytotoxicity.

  19. New DNA adducts of crotonaldehyde and acetaldehyde.

    Science.gov (United States)

    Hecht, S S; McIntee, E J; Wang, M

    2001-09-14

    This paper summarizes our recent studies on adducts produced in the reactions of the carcinogens crotonaldehyde (2-butenal) and acetaldehyde with deoxyguanosine (dG) and DNA. Human exposure to these carcinogens can be considerable, from both exogenous and endogenous sources. Crotonaldehyde reacts with DNA to form Michael addition products, a pathway that has been well described. We describe a second major pathway, in which 3-hydroxybutanal, formed by addition of H(2)O to crotonaldehyde, reacts with DNA to produce the Schiff base N(2)-(3-hydroxybut-1-ylidene)dG as well as several diastereomers of N(2)-paraldol-dG. Acetaldehyde reacts with DNA and dG giving a major Schiff base adduct, N(2)-ethylidene-dG. A cross-linked adduct of acetaldehyde has been characterized for the first time, and other adducts resulting from the reaction of two and three molecules of acetaldehyde with dG have been observed. The results of these studies demonstrate that some structurally unique adducts are formed from these carcinogenic aldehydes and suggest some new directions for research on the potential role of aldehydes in human cancer.

  20. LC-MS/MS screening strategy for unknown adducts to N-terminal valine in hemoglobin applied to smokers and nonsmokers.

    Science.gov (United States)

    Carlsson, Henrik; von Stedingk, Hans; Nilsson, Ulrika; Törnqvist, Margareta

    2014-12-15

    Electrophilically reactive compounds have the ability to form adducts with nucleophilic sites in DNA and proteins, constituting a risk for toxic effects. Mass spectrometric detection of adducts to N-terminal valine in hemoglobin (Hb) after detachment by modified Edman degradation procedures is one approach for in vivo monitoring of exposure to electrophilic compounds/metabolites. So far, applications have been limited to one or a few selected reactive species, such as acrylamide and its metabolite glycidamide. This article presents a novel screening strategy for unknown Hb adducts to be used as a basis for an adductomic approach. The method is based on a modified Edman procedure, FIRE, specifically developed for LC-MS/MS analysis of N-terminal valine adducts in Hb detached as fluorescein thiohydantoin (FTH) derivatives. The aim is to detect and identify a priori unknown Hb adducts in human blood samples. Screening of valine adducts was performed by stepwise scanning of precursor ions in small mass increments, monitoring four fragments common for the FTH derivative of valine with different N-substitutions in the multiple-reaction mode, covering a mass range of 135 Da (m/z 503-638). Samples from six smokers and six nonsmokers were analyzed. Control experiments were performed to compare these results with known adducts and to check for artifactual formation of adducts. In all samples of smokers and nonsmokers, seven adducts were identified, of which six have previously been studied. Nineteen unknown adducts were observed, and 14 of those exhibited fragmentation patterns similar to earlier studied FTH derivatives of adducts to valine. Identification of the unknown adducts will be the focus of future work. The presented methodology is a promising screening tool using Hb adducts to indicate exposure to potentially toxic electrophilic compounds and metabolites.

  1. Effects of Individualized Assignments on Biology Achievement.

    Science.gov (United States)

    Kremer, Philip L.

    1983-01-01

    Compared detailed (favoring field dependence and induction) and nondetailed (favoring field dependence and deduction) assignments on biology achievement of grade 10 male students (N=95) over a seven-month period. Detailed assignments, employing pictorial and verbal block diagrams and high structure, significantly enhanced learning among some…

  2. The Biological Effects of Nonionizing Radiation.

    Science.gov (United States)

    1981-12-29

    surrounding C-12-81 normal tissues. According to N.W. Bleehan, this was the method used by Hippocrates , with the aid of a hot iron. Hippocrates , by the way, is...temporal pattern of desired increases of tempera - ture in the body; (2) the biological consequences of doing this must be established and evaluated

  3. Technology Rich Biology Labs: Effects of Misconceptions.

    Science.gov (United States)

    Kuech, Robert; Zogg, Gregory; Zeeman, Stephan; Johnson, Mark

    This paper describes a study conducted on the lab sections of the general biology course for non-science majors at the University of New England, and reports findings of student misconceptions about photosynthesis and the mass/carbon uptake during plant growth. The current study placed high technology analytic tools in the hands of introductory…

  4. Structural water cluster as a possible proton acceptor in the adduct decay reaction of oat phototropin 1 LOV2 domain.

    Science.gov (United States)

    Chan, Ruby H; Bogomolni, Roberto A

    2012-09-06

    LOV domains (Light, Oxygen, Voltage) are the light-sensory modules of phototropins, the blue-light photoreceptor kinases in plants, and of a wide variety of flavoproteins found in all three domains of life. These 12 kDa modules bind a flavin chromophore (FMN or FAD) noncovalently and undergo a photochemical activation in which the sulfur atom of a conserved cysteine forms an adduct to the C(4a) carbon of the flavin. The adduct breaks spontaneously in a base-catalyzed reaction involving a rate-limiting proton-transfer step, regenerating the dark state in seconds. This photocycle involves chromophore and protein structural changes that activate the C-terminal serine/threonine kinase. Previous studies (Biochemistry 2007, 46, 7016-7021) showed that decreased hydration obtained at high glycerol concentrations stabilizes the adduct state in a manner similar to that attained at low temperatures, resulting in much longer adduct decay times. This kinetic effect was attributed to an increased protein rigidity that hindered structural fluctuations necessary for the decay reaction. In this work, we studied the adduct decay kinetics of oat phototropin 1 (phot1) LOV2 at varying hydration using a specially designed chamber that allowed for measurement of UV-visible and FTIR spectra of the same samples. Therefore, we obtained LOV protein concentrations, adduct decay kinetics, and the different populations of bound water by deconvolution of the broad water absorption peak around 3500 cm(-1). A linear dependence of the adduct decay rate constant on the concentration of double and triple hydrogen-bonded waters strongly suggests that the adduct decay is a pseudo-first-order reaction in which both the adduct and the strongly bound waters are reactants. We suggest that a cluster of strongly bound water functions as the proton acceptor in the rate-limiting step of adduct decay.

  5. Hip adduction and abduction strength profiles in elite soccer players

    DEFF Research Database (Denmark)

    Serner, Andreas; Petersen, Jesper; Madsen, Thomas Moller

    2011-01-01

    An ipsilateral hip adduction/abduction strength ratio of more than 90%, and hip adduction strength equal to that of the contralateral side have been suggested to clinically represent adequate strength recovery of hip adduction strength in athletes after groin injury. However, to what extent side-......-to-side symmetry in isometric hip adduction and abduction strength can be assumed in soccer players remains uncertain....

  6. Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer.

    Science.gov (United States)

    Egner, P A; Wang, J B; Zhu, Y R; Zhang, B C; Wu, Y; Zhang, Q N; Qian, G S; Kuang, S Y; Gange, S J; Jacobson, L P; Helzlsouer, K J; Bailey, G S; Groopman, J D; Kensler, T W

    2001-12-04

    Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part from consumption of foods contaminated with aflatoxins. Chlorophyllin, a mixture of semisynthetic, water-soluble derivatives of chlorophyll that is used as a food colorant and over-the-counter medicine, has been shown to be an effective inhibitor of aflatoxin hepatocarcinogenesis in animal models by blocking carcinogen bioavailability. In a randomized, double-blind, placebo-controlled chemoprevention trial, we tested whether chlorophyllin could alter the disposition of aflatoxin. One hundred and eighty healthy adults from Qidong were randomly assigned to ingest 100 mg of chlorophyllin or a placebo three times a day for 4 months. The primary endpoint was modulation of levels of aflatoxin-N(7)-guanine adducts in urine samples collected 3 months into the intervention measured by using sequential immunoaffinity chromatography and liquid chromatography-electrospray mass spectrometry. This aflatoxin-DNA adduct excretion product serves as a biomarker of the biologically effective dose of aflatoxin, and elevated levels are associated with increased risk of liver cancer. Adherence to the study protocol was outstanding, and no adverse events were reported. Aflatoxin-N(7)-guanine could be detected in 105 of 169 available samples. Chlorophyllin consumption at each meal led to an overall 55% reduction (P = 0.036) in median urinary levels of this aflatoxin biomarker compared with those taking placebo. Thus, prophylactic interventions with chlorophyllin or supplementation of diets with foods rich in chlorophylls may represent practical means to prevent the development of hepatocellular carcinoma or other environmentally induced cancers.

  7. Compact bis-adduct fullerenes and additive-assisted morphological optimization for efficient organic photovoltaics.

    Science.gov (United States)

    Lai, Yun-Yu; Liao, Ming-Hung; Chen, Yen-Ting; Cao, Fong-Yi; Hsu, Chain-Shu; Cheng, Yen-Ju

    2014-11-26

    Bis-adduct fullerenes surrounded by two insulating addends sterically attenuate intermolecular interaction and cause inferior electron transportation. In this research, we have designed and synthesized a new class of bis-adduct fullerene materials, methylphenylmethano-C60 bis-adduct (MPC60BA), methylthienylmethano-C60 bis-adduct (MTC60BA), methylphenylmethano-C70 bis-adduct (MPC70BA), and methylthienylmethano-C70 bis-adduct (MTC70BA), functionalized with two compact phenylmethylmethano and thienylmethylmethano addends via cyclopropyl linkages. These materials with much higher-lying lowest unoccupied molecular orbital (LUMO) energy levels successfully enhanced the Voc values of the P3HT-based solar cell devices. The compact phenylmethylmethano and thienylmethylmethano addends to promote fullerene intermolecular interactions result in aggregation-induced phase separation as observed by the atomic force microscopy (AFM) and transmission electron microscopy (TEM) images of the poly(3-hexylthiophene-2,5-diyl) (P3HT)/bis-adduct fullerene thin films. The device based on the P3HT/MTC60BA blend yielded a Voc of 0.72 V, a Jsc of 5.87 mA/cm(2), and a fill factor (FF) of 65.3%, resulting in a power conversion efficiency (PCE) of 2.76%. The unfavorable morphologies can be optimized by introducing a solvent additive to fine-tune the intermolecular interactions. 1-Chloronaphthalene (CN) having better ability to dissolve the bis-adduct fullerenes can homogeneously disperse the fullerene materials into the P3HT matrix. Consequently, the aggregated fullerene domains can be alleviated to reach a favorable morphology. With the assistance of CN additive, the P3HT/MTC60BA-based device exhibited enhanced characteristics (a Voc of 0.78 V, a Jsc of 9.04 mA/cm(2), and an FF of 69.8%), yielding a much higher PCE of 4.92%. More importantly, the additive-assisted morphological optimization is consistently effective to all four compact bis-adduct fullerenes regardless of the methylphenylmethano

  8. Non-Thermal Effects Mobile Phones at Biological Objects

    OpenAIRE

    Ladislav Balogh

    2003-01-01

    The article deals with non-thermal effects of mobile phones on biological objects. Even though these effects are observed for longer period, there are not so far unequivocal results on obtained biological and biophysical results in this field. Biologicaleffects of electromagnetic field (EMF) depend on its character, its duration as well as on features of organism. As the receptors offield are not known (e.g. inputs of EMF into organism), its effects are judged only by non-specific reaction of...

  9. 40 CFR 721.4590 - Mannich-based adduct.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Mannich-based adduct. 721.4590 Section... Substances § 721.4590 Mannich-based adduct. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance generically identified as a Mannich-based adduct (PMN P-93-66)...

  10. Hip adduction and abduction strength profiles in elite soccer players

    DEFF Research Database (Denmark)

    Thorborg, Kristian; Serner, Andreas; Petersen, Jesper;

    2011-01-01

    An ipsilateral hip adduction/abduction strength ratio of more than 90%, and hip adduction strength equal to that of the contralateral side have been suggested to clinically represent adequate strength recovery of hip adduction strength in athletes after groin injury. However, to what extent side...

  11. Topical Day on Biological Effects of Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Baatout, S.; Jacquet, P.

    1997-05-15

    The topical day has been focussed on the potential effects of ionizing radiation on human health. A general overview on molecular and biophysical aspects of radiation, its effects on cells and organisms, and the contribution of radiobiology to radiation protection and risk assessment is given. The genetic effects of radiation and its effects on the developing organism, the effects of radiation on the cell cycle and the mechanisms of radiation induced apoptosis were also discussed.

  12. STUDY ON GMA-DNA ADDUCTS

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Objective. DNA modification fixed as mutations in the cells may be an essential factor in the initiation step of chemical carcinogenesis. In order to explore the mechanism of gene mutation and cell transformation induced by glycidyl methacrylate (GMA), the current test studied the characteristics of GMA-DNA adducts formation in vitro.Methods. In vitro test, dAMP, dCMP, dGMP, dTMP and calf thymus DNA were allowed to react with GMA (Glycidyl Methacrylate). After the reaction, the mixtures were detected by UV and subjected to reversed-phase HPLC on ultrasphere ODS reversed-phase column, the reaction products were eluted with a linear gradients of methanol (solvent A) and 10mmol/L ammonium formate, pH5.0 (solvent B). The synthesized adducts were then characterized by UV spectroscopy in acid (pH1.0), neutral (pH7.2), alkaline (pH11.0) and by mass spectroscopy.Results. The results showed that GMA could bind with dAMP, dCMP, dGMP and calf thymus DNA by covalent bond, and the binding sites were specific (N6 of adenine, N3 of cytosine). Meanwhile, a main GMA-DNA adduct in the reaction of GMA with calf thymus DNA was confirmed as N3-methacrylate-2-hydroxypropy1-dCMP.Conclusions. GMA can react with DNA and /or deoxynucleotide monophosphate and generate some adducts such as N6-methacrylate-2-hydroxypropyl-dAMP and N3-methacrylate-2-hydroxypropyl-dCMP, ets. Formation of GMA-DNA adducts is an important molecular event in gene mutation and cell transformation induced by GMA.

  13. Iron diminishes the in vitro biological effect of vanadium.

    Science.gov (United States)

    Mechanistic pathways underlying inflammatory injury following exposures to vanadium-containing compounds are not defined. We tested the postulate that the in vitro biological effect of vanadium results from its impact on iron homeostasis. Human bronchial epithelial (HBE) cells ex...

  14. Critical appraisal: dental amalgam update--part II: biological effects.

    Science.gov (United States)

    Wahl, Michael J; Swift, Edward J

    2013-12-01

    Dental amalgam restorations have been controversial for over 150 years. In Part I of this Critical Appraisal, the clinical efficacy of dental amalgam was updated. Here in Part II, the biological effects of dental amalgam are addressed.

  15. Aromatic adducts and lung cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Spanish cohort.

    Science.gov (United States)

    Gilberson, Tamra; Peluso, Marco E M; Munia, Armelle; Luján-Barroso, Leila; Sánchez, María-José; Navarro, Carmen; Amiano, Pilar; Barricarte, Aurelio; Quirós, J Ramón; Molina-Montes, Esther; Sánchez-Cantalejo, Emilio; Tormo, María-José; Chirlaque, María-Dolores; Ardanaz, Eva; Dorronsoro, Miren; Confortini, Massimo; Bonet, Catalina; Sala, Núria; González, Carlos A; Agudo, Antonio

    2014-09-01

    In this case-cohort study, we examined the association between bulky DNA adducts and the risk of lung cancer within the European Prospective Investigation into Cancer and Nutrition (EPIC) Spanish cohort with an average 7-year follow-up, including 98 cases of primary lung cancer and 296 subjects randomly selected from the cohort. Aromatic adducts were measured using (32)P-postlabeling in leukocyte DNA from blood samples collected at enrollment. The association between DNA adducts and the risk of lung cancer was estimated using a Cox proportional hazards model with a modified partial likelihood. There was an overall significant increased risk for developing lung cancer when DNA adduct concentrations were doubled, with relative risk (RR) adjusting for all relevant confounders of 1.36 with 95% confidence interval (CI) 1.18-157. There was a significant increased risk for developing lung cancer when DNA adduct concentrations were doubled for current smokers and among subjects exposed to PAH at work; there was also a slightly higher increase among males than females. However, no statistically significant differences were observed for the effect of adduct levels across smoking status, sex or occupational exposure to PAH. A meta-analysis combined four prospective studies, including this study, resulting in a significant association among current smokers, with an overall estimate of 34% increase in the risk of lung cancer when doubling the level of aromatic DNA adducts in leukocytes.

  16. Hormesis [Biological Effects of Low Level Exposures (Belle)] and Dermatology

    OpenAIRE

    Thong, Haw-Yueh; Maibach, Howard I.

    2008-01-01

    Hormesis, or biological effects of low level exposures (BELLE), is characterized by nonmonotonic dose response which is biphasic, displaying opposite effects at low and high dose. Its occurrence has been documented across a broad range of biological models and diverse type of exposure. Since hormesis appears to be a relatively common phenomenon in many areas, the objective of this review is to explore its occurrence related to dermatology and its public health and risk assessment implication....

  17. Biological effects of exposure to magnetic resonance imaging: an overview

    OpenAIRE

    Formica Domenico; Silvestri Sergio

    2004-01-01

    Abstract The literature on biological effects of magnetic and electromagnetic fields commonly utilized in magnetic resonance imaging systems is surveyed here. After an introduction on the basic principles of magnetic resonance imaging and the electric and magnetic properties of biological tissues, the basic phenomena to understand the bio-effects are described in classical terms. Values of field strengths and frequencies commonly utilized in these diagnostic systems are reported in order to a...

  18. Contribution of artifacts to N-methylated piperazine cyanide adduct formation in vitro from N-alkyl piperazine analogs.

    Science.gov (United States)

    Zhang, Minli; Resuello, Christina M; Guo, Jian; Powell, Mark E; Elmore, Charles S; Hu, Jun; Vishwanathan, Karthick

    2013-05-01

    In the liver microsome cyanide (CN)-trapping assays, piperazine-containing compounds formed significant N-methyl piperazine CN adducts. Two pathways for the N-methyl piperazine CN adduct formation were proposed: 1) The α-carbon in the N-methyl piperazine is oxidized to form a reactive iminium ion that can react with cyanide ion; 2) N-dealkylation occurs followed by condensation with formaldehyde and dehydration to produce N-methylenepiperazine iminium ion, which then reacts with cyanide ion to form the N-methyl CN adduct. The CN adduct from the second pathway was believed to be an artifact or metabonate. In the present study, a group of 4'-N-alkyl piperazines and 4'-N-[¹³C]methyl-labeled piperazines were used to determine which pathway was predominant. Following microsomal incubations in the presence of cyanide ions, a significant percentage of 4'-N-[¹³C]methyl group in the CN adduct was replaced by an unlabeled natural methyl group, suggesting that the second pathway was predominant. For 4'-N-alkyl piperazine, the level of 4'-N-methyl piperazine CN adduct formation was limited by the extent of prior 4'-N-dealkylation. In a separate study, when 4'-NH-piperaziens were incubated with potassium cyanide and [¹³C]-labeled formaldehyde, 4'-N-[¹³C]methyl piperazine CN-adduct was formed without NADPH or liver microsome suggesting a direct Mannich reaction is involved. However, when [¹³C]-labeled methanol or potassium carbonate was used as the one-carbon donor, 4'-N-[¹³C]methyl piperazine CN adduct was not detected without liver microsome or NADPH present. The biologic and toxicological implications of bioactivation via the second pathway necessitate further investigation because these one-carbon donors for the formation of reactive iminium ions could be endogenous and readily available in vivo.

  19. Formation of DNA Adducts by Ellipticine and Its Micellar Form in Rats — A Comparative Study

    Directory of Open Access Journals (Sweden)

    Marie Stiborova

    2014-12-01

    Full Text Available The requirements for early diagnostics as well as effective treatment of cancer diseases have increased the pressure on development of efficient methods for targeted drug delivery as well as imaging of the treatment success. One of the most recent approaches covering the drug delivery aspects is benefitting from the unique properties of nanomaterials. Ellipticine and its derivatives are efficient anticancer compounds that function through multiple mechanisms. Formation of covalent DNA adducts after ellipticine enzymatic activation is one of the most important mechanisms of its pharmacological action. In this study, we investigated whether ellipticine might be released from its micellar (encapsulated form to generate covalent adducts analogous to those formed by free ellipticine. The 32P-postlabeling technique was used as a useful imaging method to detect and quantify covalent ellipticine-derived DNA adducts. We compared the efficiencies of free ellipticine and its micellar form (the poly(ethylene oxide-block-poly(allyl glycidyl ether (PAGE-PEO block copolymer, P 119 nanoparticles to form ellipticine-DNA adducts in rats in vivo. Here, we demonstrate for the first time that treatment of rats with ellipticine in micelles resulted in formation of ellipticine-derived DNA adducts in vivo and suggest that a gradual release of ellipticine from its micellar form might produce the enhanced permeation and retention effect of this ellipticine-micellar delivery system.

  20. Biological Effects of the Great Oxidation Event

    Science.gov (United States)

    Schopf, J.

    2012-12-01

    Fossil evidence of photoautotrophy, documented in Precambrian sediments by stromatolites, stromatolitic microfossils, and carbon isotopic data consistent with autotrophic CO2-fixation, extends to ~3,500 Ma. Such data, however, are insufficient to establish the time of origin of O2-producing (cyanobacterial) photosynthesis from its anoxygenic, photosynthetic bacterial, evolutionary precursor. The oldest (Paleoarchean) stromatolites may have been formed by anoxygenic photoautotrophs, rather than the cyanobacteria that dominate Proterozoic and modern stromatolites. Unlike the cyanobacteria of Proterozoic microbial assemblages, the filamentous and coccoidal microfossils of Archean deposits may represent remnants of non-O2-producing prokaryotes. And although the chemistry of Archean organic matter shows it to be biogenic, its carbon isotopic composition is insufficient to differentiate between oxygenic and anoxygenic sources. Though it is well established that Earth's ecosystem has been based on autotrophy since its early stages and that O2-producing photosynthesis evolved earlier, perhaps much earlier, than the increase of atmospheric oxygen in the ~2,450 and ~2,320 Ma Great Oxidation Event (GOE), the time of origin of oxygenic photoautotrophy has yet to be established. Recent findings suggest that Earth's ecosystem responded more or less immediately to the GOE. The increase of atmospheric oxygen markedly affected ocean water chemistry, most notably by increasing the availability of biologically usable oxygen (which enabled the development of obligate aerobes, such as eukaryotes), and of nitrate, sulfate and hydrogen sulfide (the increase of H2S being a result of microbial reduction of sulfate), the three reactants that power the anaerobic basis of sulfur-cycling microbial sulfuretums. Fossil evidence of the earliest eukaryotes (widely accepted to date from ~1800 Ma and, arguably, ~2200 Ma) fit this scenario, but the most telling example of life's response to the GOE

  1. Inhibition of nicotine-DNA adduct formation by polyphenolic compounds in vitro

    Institute of Scientific and Technical Information of China (English)

    CHENG Yan; WANG Hai-Fang; SUN Hong-Fang; LI Hong-Li

    2004-01-01

    Nicotine [3-(1-methyl-2-pyrrolidinyl)-pyridine], a major alkaloid in tobacco products, has proven to be a potential genotoxic compound. Some polyphenolic compounds can suppress the DNA adduction, and hence act as the potential inhibitors of carcinogenesis. In this study, the inhibitory effects of three polyphenolic compounds, curcumin (diferuloylmethane), resveratrol (trans-3, 5, 4-trihydroxystilbene) and tea polyphenols, on the nicotine-DNA adduction have been investigated in vitro using radiolabelled nicotine and liquid scintillation counting (LSC) technique. Also, the inhibition mechanism of these chemopreventive agents in regard to the activity of the biotransformation enzymes, including cytochrome P450 (CYP450), cytochrome b5 (CYb5) and glutathione S-transferase (GST), has been studied. The results demonstrated that these three polyphenols induced marked dose-dependent decrease in nicotine-DNA adducts as compared with the controls. The elimination rate of adducts reached above 46% at the highest dose for all the three agents with 51.6% for resveratrol. Correspondingly, three polyphenols all suppressed CYP450 and CYb5, whereas curcumin and resveratrol induced GST. We may arrive at a point that the three polyphenols are beneficial to prevent the nicotine adduct formation, and thus may be used to block the potential carcinogenesis induced by nicotine.

  2. The long persistence of pyrrolizidine alkaloid-derived DNA adducts in vivo: kinetic study following single and multiple exposures in male ICR mice.

    Science.gov (United States)

    Zhu, Lin; Xue, Junyi; Xia, Qingsu; Fu, Peter P; Lin, Ge

    2017-02-01

    Pyrrolizidine alkaloid (PA)-containing plants are widespread in the world and the most common poisonous plants affecting livestock, wildlife, and humans. Our previous studies demonstrated that PA-derived DNA adducts can potentially be a common biological biomarker of PA-induced liver tumor formation. In order to validate the use of these PA-derived DNA adducts as a biomarker, it is necessary to understand the basic kinetics of the PA-derived DNA adducts formed in vivo. In this study, we studied the dose-dependent response and kinetics of PA-derived DNA adduct formation and removal in male ICR mice orally administered with a single dose (40 mg/kg) or multiple doses (10 mg/kg/day) of retrorsine, a representative carcinogenic PA. In the single-dose exposure, the PA-derived DNA adducts exhibited dose-dependent linearity and persisted for up to 4 weeks. The removal of the adducts following a single-dose exposure to retrorsine was biphasic with half-lives of 9 h (t 1/2α) and 301 h (~12.5 days, t 1/2β). In the 8-week multiple exposure study, a marked accumulation of PA-derived DNA adducts without attaining a steady state was observed. The removal of adducts after the multiple exposure also demonstrated a biphasic pattern but with much extended half-lives of 176 h (~7.33 days, t 1/2α) and 1736 h (~72.3 days, t 1/2β). The lifetime of PA-derived DNA adducts was more than 8 weeks following the multiple-dose treatment. The significant persistence of PA-derived DNA adducts in vivo supports their role in serving as a biomarker of PA exposure.

  3. Effect of hepatic cytochrome P450 (P450) oxidoreductase deficiency on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-DNA adduct formation in P450 reductase conditional null mice.

    Science.gov (United States)

    Arlt, Volker M; Singh, Rajinder; Stiborová, Marie; Gamboa da Costa, Gonçalo; Frei, Eva; Evans, James D; Farmer, Peter B; Wolf, C Roland; Henderson, Colin J; Phillips, David H

    2011-12-01

    2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), formed during the cooking of foods, induces colon cancer in rodents. PhIP is metabolically activated by cytochromes P450 (P450s). To evaluate the role of hepatic P450s in the bioactivation of PhIP, we used Reductase Conditional Null (RCN) mice, in which cytochrome P450 oxidoreductase (POR), the unique electron donor to P450s, can be specifically deleted in hepatocytes by pretreatment with 3-methylcholanthrene (3-MC), resulting in the loss of essentially all hepatic P450 function. RCN mice were treated orally with 50 mg/kg b.wt. PhIP daily for 5 days, with and without 3-MC pretreatment. PhIP-DNA adducts (i.e., N-(deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine [dG-C8-PhIP]), measured by liquid chromatography-tandem mass spectrometry, were highest in colon (1362 adducts/10(8) deoxynucleosides), whereas adduct levels in liver were ∼3.5-fold lower. Whereas no differences in PhIP-DNA adduct levels were found in livers with active POR versus inactivated POR, adduct levels were on average ∼2-fold lower in extrahepatic tissues of mice lacking hepatic POR. Hepatic microsomes from RCN mice with or without 3-MC pretreatment were also incubated with PhIP and DNA in vitro. PhIP-DNA adduct formation was ∼8-fold lower with hepatic microsomes from POR-inactivated mice than with those with active POR. Most of the hepatic microsomal activation of PhIP in vitro was attributable to CYP1A. Our results show that PhIP-DNA adduct formation in colon involves hepatic N-oxidation, circulation of activated metabolites via the bloodstream to extrahepatic tissues, and further activation, resulting in the formation of dG-C8-PhIP. Besides hepatic P450s, PhIP may be metabolically activated mainly by a non-P450 pathway in liver.

  4. Lysine adducts between methyltetrahydrophthalic anhydride and collagen in guinea pig lung.

    Science.gov (United States)

    Jönsson, B A; Wishnok, J S; Skipper, P L; Stillwell, W G; Tannenbaum, S R

    1995-11-01

    The formation of adducts between methyltetrahydrophthalic anhydride (MTHPA), an important industrial chemical and potent allergen, and collagen from guinea pig lung tissue was investigated. Collagen peptides were obtained from the lung tissue by homogenization, defatting, washing, and digestion with collagenase. In experiments in vitro, lung tissue was exposed to 8.4 mumol (50 microCi) of 14C MTHPA. The amount of adducts was 97 nmol MTHPA/g of wet tissue as determined from the bound radioactivity. In a study in vivo, four guinea pigs were injected intratracheally with 8.4 mumol of 14C MTHPA each. The amount of adducts was 0-1.2 nmol MTHPA/g of wet tissue (determined by bound radioactivity). N epsilon-methyltetrahydrophthaloyl-L-lysine (MTHPL) was synthesized and characterized by NMR, UV, and mass spectrometry (MS). A method to analyze MTHPL, after derivatization with methanol and pentafluorobenzoyl chloride, using gas chromatography-MS was developed. Analysis of Pronase-digested MTHPA-exposed lung tissue showed a concentration of 19 nmol MTHPL/g wet lung in vitro and between 0 and 0.15 nmol MTHPL/g wet lung in vivo. Thus, 20% in vitro and 12-15% in vivo of the bound radioactivity was found as adducts with lysine. These results are a first step toward studies of allergenic epitopes in proteins and methods for biological monitoring of exposure to acid anhydrides.

  5. Biological effects of fruit and vegetables

    DEFF Research Database (Denmark)

    Dragsted, L. O.; Krath, B.; Ravn-Haren, Gitte;

    2006-01-01

    , providing 600hairspg fruit and vegetables/d or in the controls a carbohydrate-rich drink to balance energy intake. Surrogate markers of oxidative damage to DNA, protein and lipids, enzymic defence and lipid metabolism were determined in blood and urine. It was found that a high intake of fruit......A strong and persistent effect of plant-derived foods on the prevention of lifestyle diseases has emerged from observational studies. Several groups of constituents in plants have been identified as potentially health promoting in animal studies, including cholesterol-lowering factors, antioxidants......, enzyme inducers, apoptosis inducers etc. In human intervention studies the dose levels achieved tend to be lower than the levels found to be effective in animals and sampling from target organs is often not possible. A controlled dietary human intervention study was performed with forty-three volunteers...

  6. Biological and therapeutical effects of Radon

    Energy Technology Data Exchange (ETDEWEB)

    Deetjen, P. [Institute of Physiologie and Balneologie, University of Innsbruck (Austria)

    1998-12-31

    In spas with a somewhat elevated Radon{sup 222} (Rn) activity (between 300 and 3000 Bq/l), the empirical medicine ended - in all parts of the world - with the same list of indications. It mainly includes the more painful rheumatic diseases such as deformation or degeneration of the joints and non bacterial inflammation of muscles, tendons or joints; Morbus Bechterew and other diseases of the vertebral column like spondylosis, spondylarthrosis or osteochondrosis. While informer times these effects were seldom documented in an objective manner, in recent years several prospective randomized double-blind studies proved the pain reducing efficacy of Radon therapy in patients with cervical pain syndromes, with chronic polyarthritis or with Morbus Bechterew. Studies in experimental animal models have accumulated remarkable data in organs, tissue and cultured cells that provide a rationale to explain the observed effects of Radon therapy in patients. (author)

  7. Efficient CO2 capture by tertiary amine-functionalized ionic liquids through Li+-stabilized zwitterionic adduct formation

    OpenAIRE

    Yang, Zhen-zhen; He, Liang-Nian

    2014-01-01

    Highly efficient CO2 absorption was realized through formation of zwitterionic adducts, combining synthetic strategies to ionic liquids (ILs) and coordination. The essence of our strategy is to make use of multidentate cation coordination between Li+ and an organic base. Also PEG-functionalized organic bases were employed to enhance the CO2-philicity. The ILs were reacted with CO2 to form the zwitterionic adduct. Coordination effects between various lithium salts and neutral ligands, as well ...

  8. Palytoxin and Analogs: Biological and Ecological Effects

    Directory of Open Access Journals (Sweden)

    Vítor Ramos

    2010-06-01

    Full Text Available Palytoxin (PTX is a potent marine toxin that was originally found in soft corals from tropical areas of the Pacific Ocean. Soon after, its occurrence was observed in numerous other marine organisms from the same ecological region. More recently, several analogs of PTX were discovered, remarkably all from species of the dinoflagellate genus Ostreopsis. Since these dinoflagellates are also found in other tropical and even in temperate regions, the formerly unsuspected broad distribution of these toxins was revealed. Toxicological studies with these compounds shows repeatedly low LD50 values in different mammals, revealing an acute toxic effect on several organs, as demonstrated by different routes of exposure. Bioassays tested for some marine invertebrates and evidences from environmental populations exposed to the toxins also give indications of the high impact that these compounds may have on natural food webs. The recognition of its wide distribution coupled with the poisoning effects that these toxins can have on animals and especially on humans have concerned the scientific community. In this paper, we review the current knowledge on the effects of PTX and its analogs on different organisms, exposing the impact that these toxins may have in coastal ecosystems.

  9. Linking exposure to environmental pollutants with biological effects

    DEFF Research Database (Denmark)

    Sørensen, Mette; Autrup, Herman; Møller, Peter

    2003-01-01

    Exposure to ambient air pollution has been associated with cancer. Ambient air contains a complex mixture of toxics, including particulate matter (PM) and benzene. Carcinogenic effects of PM may relate both to the content of PAH and to oxidative DNA damage generated by transition metals, benzene......, metabolism and inflammation. By means of personal monitoring and biomarkers of internal dose, biologically effective dose and susceptibility, it should be possible to characterize individual exposure and identify air pollution sources with relevant biological effects. In a series of studies, individual......, biological effects of air pollutants appear mainly related to oxidative stress via personal exposure and not to urban background levels. Future developments include personal time-resolved monitors for exposure to ultrafine PM and PM(2.5,) use of GPS, as well as genomics and proteomics based biomarkers....

  10. Biological effects of stellar collapse neutrinos

    CERN Document Server

    Collar, J I

    1996-01-01

    Massive stars in their final stages of collapse radiate most of their binding energy in the form of MeV neutrinos. The recoil atoms that they produce in elastic scattering off nuclei in organic tissue create a radiation damage which is highly effective in the production of irreparable DNA harm, leading to cellular mutation, neoplasia and oncogenesis. Using a conventional model of the galaxy and of the collapse mechanism, the periodicity of nearby stellar collapses and the radiation dose are calculated. The possible contribution of this process to the paleontological record of mass extinctions is examined.

  11. Biological monitoring the exposure to polycyclic aromatic hydrocarbons of coke oven workers in relation to smoking and genetic polymorphisms for GSTM1 GSTT1

    NARCIS (Netherlands)

    Delft, J.H.M. van; Steenwinkel, M.-J.S.T.; Asten, J.G. van; Vogel, N. de; Bruijntjes-Rozier, T.C.D.M.; Schouten, T.; Cramers, P.; Maas, L.; Herwijnen, M.H. van; Schooten, F.-J. van; Hopmans, P.M.J.

    2001-01-01

    Occupational exposure to polycyclic aromatic hydrocarbons (PAH) increases the risk of developing lung cancer. Human exposure is often demonstrated by increased internal levels of PAH metabolites and of markers for early biological effects, like DNA adducts and cytogenetic aberrations. Objective: Thi

  12. Nanosilver – Harmful effects of biological activity

    Directory of Open Access Journals (Sweden)

    Anna Maria Świdwińska-Gajewska

    2014-12-01

    Full Text Available Nanosilver, also identified as colloidal silver, has been known and used for ages to combat diseases or prolong food freshness. It usually occurs in the form of a suspension consisting of particles of size < 100 nm. Due to its specific properties, silver nanoparticles are used in many technologies to produce medical devices, textiles, conductive materials or photovoltaic cells. The growing popularity of nanosilver applications increases the number of people occupationally exposed to this substance. Potential exposure routes for silver nanoparticles are through dermal, oral and inhalation pathways. Silver nanoparticles may be absorbed through the lungs, intestine, and through the skin into circulation and thus may reach such organs as the liver, kidney, spleen, brain, heart and testes. Nanosilver may cause mild eyes and skin irritations. It can also act as a mild skin allergen. Inhalation of silver nanoparticles mainly affects the lungs and liver. It has been demonstrated that silver nanoparticles may be genotoxic to mammalian cells. There are some alarming reports on the adverse effects of silver nanoparticles on reproduction of experimental animals. Exposure to silver nanoparticles may exert a neurotoxic effect and affect cognitive functions, causing the impairment of short-term and working memory. Maximum admissible concentration (MAC for the inhalable fraction of silver of 0.05 mg/m3 is currently binding in Poland. In light of toxicological studies of silver nanoparticles it seems reasonable to update the hygiene standards for silver with nanoparticles as a separate fraction. Med Pr 2014;65(6:831–845

  13. Electromagnetic field induced biological effects in humans.

    Science.gov (United States)

    Kaszuba-Zwoińska, Jolanta; Gremba, Jerzy; Gałdzińska-Calik, Barbara; Wójcik-Piotrowicz, Karolina; Thor, Piotr J

    2015-01-01

    Exposure to artificial radio frequency electromagnetic fields (EMFs) has increased significantly in recent decades. Therefore, there is a growing scientific and social interest in its influence on health, even upon exposure significantly below the applicable standards. The intensity of electromagnetic radiation in human environment is increasing and currently reaches astronomical levels that had never before experienced on our planet. The most influential process of EMF impact on living organisms, is its direct tissue penetration. The current established standards of exposure to EMFs in Poland and in the rest of the world are based on the thermal effect. It is well known that weak EMF could cause all sorts of dramatic non-thermal effects in body cells, tissues and organs. The observed symptoms are hardly to assign to other environmental factors occurring simultaneously in the human environment. Although, there are still ongoing discussions on non-thermal effects of EMF influence, on May 31, 2011--International Agency for Research on Cancer (IARC)--Agenda of World Health Organization (WHO) has classified radio electromagnetic fields, to a category 2B as potentially carcinogenic. Electromagnetic fields can be dangerous not only because of the risk of cancer, but also other health problems, including electromagnetic hypersensitivity (EHS). Electromagnetic hypersensitivity (EHS) is a phenomenon characterized by the appearance of symptoms after exposure of people to electromagnetic fields, generated by EHS is characterized as a syndrome with a broad spectrum of non-specific multiple organ symptoms including both acute and chronic inflammatory processes located mainly in the skin and nervous systems, as well as in respiratory, cardiovascular systems, and musculoskeletal system. WHO does not consider the EHS as a disease-- defined on the basis of medical diagnosis and symptoms associated with any known syndrome. The symptoms may be associated with a single source of EMF

  14. Biological effect of radiation on human

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yun Sil; Cho, Chul Koo; Lee, Su Jae [and others

    2000-04-01

    1. Adaptive response when 0.01 Gy was preirradiated before high challenging dose is induced in normal cell types such normal lymphocytes, primary keratinocytes, and L929 fibroblast cells but not in neoplastic cells such as L5178Y lymphoma cells, EL-4 lymphoma cells and 308 papilloma cells. 2. Heat shock protein (HSP) 25 and inducible HSP70 is responsible for the induction of adaptive response and radioresistance - cell cycle regulation, antiapoptotic molecule and PKC activation were involved. 3. Apoptosis was induced at most 5. hrs after irradiation in primary keratinocytes, in v-rasHa transformed keratinocytes, the maximum interval was 16 hrs, and in 308 papilloma cells, the maximum was 48 hrs. 4. PKC response by radiation is correlated with induction of apoptosis. 5. Rapid induction PKCdelta in primary keratinocytes and no response of PKC epsilon may involved in radiation induced apoptosis. 6. The rate of resorption was increased when radiation was given at 2.5 days after gestation. Early death including foetal death were highly expressed when radiation was given at 7.5 days after gestation. There are no difference in incidence of late death including embryonic death. 7. 2 Gy is the most effective dose in radiation induced teratogenesis in mouse model. 8. Growth retardation and small head was present when radiation was given at 5.5, 7.5, 11.5 and 15.5 days after gestation and small head showed high incidence at 11.5 days after gestation. 9. External malformation, internal malformation and skeletal malformation was induced when radiation was given at 7.5 days after gestation. 10. OGG1-mutated cells induced radiosensitive by G2/M cell cycle arrest. 11. Radiation induced G2/M phase cell cycle and correlated with radiosensitivity. 12. PKCalpha induced differentiation. 13. Radiation exposed cells showed carcinogenic effect. 14. Organ specific radiosensitivity was shown and protein expression was involved.

  15. A new approach to evaluating the extent of Michael adduct formation to PAH quinones: tetramethylammonium hydroxide (TMAH) thermochemolysis with GC/MS.

    Science.gov (United States)

    Briggs, Mary K; Desavis, Emmanuel; Mazzer, Paula A; Sunoj, R B; Hatcher, Susan A; Hadad, Christopher M; Hatcher, Patrick G

    2003-11-01

    Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that are converted to cytotoxic and carcinogenic metabolites, quinones, by detoxifying enzyme systems in animals. PAH metabolites such as the quinones can form Michael adducts with biological macromolecules containing reactive nucleophiles, making detection of exposure to PAHs difficult using conventional techniques. A technique has been developed for detecting exposure to PAHs. Tetramethylammonium hydroxide (TMAH) thermochemolysis coupled with GC/MS is proposed as an assay method for PAH quinones that have formed Michael adducts with biological molecules. Three PAH quinones (1,4-naphthoquinone, 1,2-naphthoquinone, and 1,4-anthraquinone) and 1,4-benzoquinone were reacted with cysteine, and the TMAH thermochemolysis method was used to assay for both thiol and amine adduction between the quinones and the cysteine. Additional studies with 1,4-naphthoquinone adducts to glutathione and bovine serum albumin showed the same thiol and amine TMAH thermochemolysis products with larger peptides as was observed with cysteine adducts. The TMAH GC/MS method clearly shows great promise for detecting PAH quinones, produced by enzymatic conversion of PAHs in biological systems, that have been converted to respective Michael adducts.

  16. Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase-mediated DNA adduct formation by heterocyclic aromatic amines in human adenocarcinoma colon cells

    NARCIS (Netherlands)

    Moonen, H.J.J.; Dommels, Y.E.M.; Zwam, M.; Herwijnen, van M.H.M.; Kleinjans, J.C.S.; Alink, G.M.; Kok, de T.M.C.M.

    2004-01-01

    Dietary heterocyclic aromatic amines (HCA) and polyunsaturated fatty acids (PUFA) are both believed to play a role in colon carcinogenesis, and are both substrate for the enzyme cyclooxygenase (COX). In HCA-7 cells, highly expressing isoform COX-2, we investigated the effects of PUFA on prostaglandi

  17. Interactions between polycyclic aromatic hydrocarbons in binary mixtures: Effects on gene expression and DNA adduct formation in precision-cut rat liver slices

    NARCIS (Netherlands)

    Staal, Y.C.M.; Pushparajah, D.S.; Herwijnen, M.H.M. van; Gottschalk, R.W.H.; Maas, L.M.; Ioannides, C.; Schooten, F.J. van; Delft, J.H.M. van

    2008-01-01

    Although exposure to polycyclic aromatic hydrocarbons (PAHs) occurs mostly through mixtures, hazard and risk assessment are mostly based on the effects caused by individual compounds. The objective of the current study was to investigate whether interactions between PAHs occur, focusing on gene expr

  18. Biologic

    CERN Document Server

    Kauffman, L H

    2002-01-01

    In this paper we explore the boundary between biology and the study of formal systems (logic). In the end, we arrive at a summary formalism, a chapter in "boundary mathematics" where there are not only containers but also extainers ><, entities open to interaction and distinguishing the space that they are not. The boundary algebra of containers and extainers is to biologic what boolean algebra is to classical logic. We show how this formalism encompasses significant parts of the logic of DNA replication, the Dirac formalism for quantum mechanics, formalisms for protein folding and the basic structure of the Temperley Lieb algebra at the foundations of topological invariants of knots and links.

  19. Third eye, the biological effects; 3. oeil, les effets biologiques

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    2004-02-01

    The discovery of a third kind of photo-receptor cell in the human eye has permitted to better understand the biological effects of lighting, not only on the vision, but also on some nervous processes, like emotion, mood, stress, biological clock, etc.. This additional dimension has led the engineers of Philips Lighting company to launch a new indoor lighting concept named 'Carpe Diem'. This concept adapts both the illuminance and the color of a lighting system according to the type of work and to the expected stimulating effect. (J.S.)

  20. Biological effect of penetration controlled irradiation with ion beams

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Atsushi; Shimizu, Takashi; Kikuchi, Masahiro; Kobayashi, Yasuhiko; Watanabe, Hiroshi [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment; Yamashita, Takao

    1997-03-01

    To investigate the effect of local irradiation with ion beams on biological systems, technique for penetration controlled irradiation has been established. The range in a target was controlled by changing the distance from beam window in the atmosphere, and could be controlled linearly up to about 31 {mu}m in biological material. In addition, the effects of the penetration controlled irradiations with 1.5 MeV/u C and He ions were examined using tobacco pollen. The increased frequency of leaky pollen produced by ion beams suggests that the efficient pollen envelope damages would be induced at the range-end of ion beams. (author)

  1. Nuclear magnetic resonance studies of an N2-guanine adduct derived from the tumorigen dibenzo[a,l]pyrene in DNA: impact of adduct stereochemistry, size, and local DNA sequence on solution conformations.

    Science.gov (United States)

    Rodríguez, Fabián A; Liu, Zhi; Lin, Chin H; Ding, Shuang; Cai, Yuqin; Kolbanovskiy, Alexander; Kolbanovskiy, Marina; Amin, Shantu; Broyde, Suse; Geacintov, Nicholas E

    2014-03-25

    The dimensions and arrangements of aromatic rings (topology) in adducts derived from the reactions of polycyclic aromatic hydrocarbon (PAH) diol epoxide metabolites with DNA influence the distortions and stabilities of double-stranded DNA, and hence their recognition and processing by the human nucleotide excision repair (NER) system. Dibenzo[a,l]pyrene (DB[a,l]P) is a highly tumorigenic six-ring PAH, which contains a nonplanar and aromatic fjord region that is absent in the structurally related bay region five-ring PAH benzo[a]pyrene (B[a]P). The PAH diol epoxide-DNA adducts formed include the stereoisomeric 14S and 14R trans-anti-DB[a,l]P-N(2)-dG and the stereochemically analogous 10S- and 10R-B[a]P-N(2)-dG (B[a]P-dG) guanine adducts. However, nuclear magnetic resonance (NMR) solution studies of the 14S-DB[a,l]P-N(2)-dG adduct in DNA have not yet been presented. Here we have investigated the 14S-DB[a,l]P-N(2)-dG adduct in two different sequence contexts using NMR methods with distance-restrained molecular dynamics simulations. In duplexes with dC opposite the adduct deleted, a well-resolved base-displaced intercalative adduct conformation can be observed. In full duplexes, in contrast to the intercalated 14R stereoisomeric adduct, the bulky DB[a,l]P residue in the 14S adduct is positioned in a greatly widened and distorted minor groove, with significant disruptions and distortions of base pairing at the lesion site and two 5'-side adjacent base pairs. These unique structural features are significantly different from those of the stereochemically analogous but smaller B[a]P-dG adduct. The greater size and different topology of the DB[a,l]P aromatic ring system lead to greater structurally destabilizing DNA distortions that are partially compensated by stabilizing DB[a,l]P-DNA van der Waals interactions, whose combined effects impact the NER response to the adduct. These structural results broaden our understanding of the structure-function relationship in NER.

  2. Prolonged Acetaminophen-Protein Adduct Elimination During Renal Failure, Lack of Adduct Removal by Hemodiafiltration, and Urinary Adduct Concentrations After Acetaminophen Overdose.

    Science.gov (United States)

    Curry, Steven C; Padilla-Jones, Angela; O'Connor, Ayrn D; Ruha, Anne-Michelle; Bikin, Dale S; Wilkins, Diana G; Rollins, Douglas E; Slawson, Matthew H; Gerkin, Richard D

    2015-06-01

    Elevated concentrations of serum acetaminophen-protein adducts, measured as protein-derived acetaminophen-cysteine (APAP-CYS), have been used to support a diagnosis of APAP-induced liver injury when histories and APAP levels are unhelpful. Adducts have been reported to undergo first-order elimination, with a terminal half-life of about 1.6 days. We wondered whether renal failure would affect APAP-CYS elimination half-life and whether continuous venovenous hemodiafiltration (CVVHDF), commonly used in liver failure patients, would remove adducts to lower their serum concentrations. Terminal elimination half-lives of serum APAP-CYS were compared between subjects with and without renal failure in a prospective cohort study of 168 adults who had ingested excessive doses of APAP. APAP-CYS concentrations were measured in plasma ultrafiltrate during CVVHDF at times of elevated serum adduct concentrations. Paired samples of urine and serum APAP-CYS concentrations were examined to help understand the potential importance of urinary elimination of serum adducts. APAP-CYS elimination half-life was longer in 15 renal failure subjects than in 28 subjects with normal renal function (41.3 ± 2.2 h versus 26.8 ± 1.1 h [mean ± SEM], respectively, p adduct elimination, and consideration of prolonged elimination needs to be considered if attempting back-extrapolation of adduct concentrations. CVVHDF did not remove detectable APAP-CYS, suggesting approximate APAP-protein adduct molecular weights ≥ 50,000 Da. The presence of urinary APAP-CYS in the minority of instances was most compatible with renal adduct production and protein shedding into urine rather than elimination of serum adducts.

  3. Insights into the conformation of aminofluorene-deoxyguanine adduct in a DNA polymerase active site.

    Science.gov (United States)

    Vaidyanathan, Vaidyanathan G; Liang, Fengting; Beard, William A; Shock, David D; Wilson, Samuel H; Cho, Bongsup P

    2013-08-09

    The active site conformation of the mutagenic fluoroaminofluorene-deoxyguanine adduct (dG-FAF, N-(2'-deoxyguanosin-8-yl)-7-fluoro-2-aminofluorene) has been investigated in the presence of Klenow fragment of Escherichia coli DNA polymerase I (Kfexo(-)) and DNA polymerase β (pol β) using (19)F NMR, insertion assay, and surface plasmon resonance. In a single nucleotide gap, the dG-FAF adduct adopts both a major-groove- oriented and base-displaced stacked conformation, and this heterogeneity is retained upon binding pol β. The addition of a non-hydrolysable 2'-deoxycytosine-5'-[(α,β)-methyleno]triphosphate (dCMPcPP) nucleotide analog to the binary complex results in an increase of the major groove conformation of the adduct at the expense of the stacked conformation. Similar results were obtained with the addition of an incorrect dAMPcPP analog but with formation of the minor groove binding conformer. In contrast, dG-FAF adduct at the replication fork for the Kfexo(-) complex adopts a mix of the major and minor groove conformers with minimal effect upon the addition of non-hydrolysable nucleotides. For pol β, the insertion of dCTP was preferred opposite the dG-FAF adduct in a single nucleotide gap assay consistent with (19)F NMR data. Surface plasmon resonance binding kinetics revealed that pol β binds tightly with DNA in the presence of correct dCTP, but the adduct weakens binding with no nucleotide specificity. These results provide molecular insights into the DNA binding characteristics of FAF in the active site of DNA polymerases and the role of DNA structure and sequence on its coding potential.

  4. "Danger" conditions increase sulfamethoxazole-protein adduct formation in human antigen-presenting cells.

    Science.gov (United States)

    Lavergne, S N; Wang, H; Callan, H E; Park, B K; Naisbitt, D J

    2009-11-01

    Antigen-presenting cells (APC) are thought to play an important role in the pathogenesis of drug-induced immune reactions. Various pathological factors can activate APC and therefore influence the immune equilibrium. It is interesting that several diseases have been associated with an increased rate of drug allergy. The aim of this project was to evaluate the impact of such "danger signals" on sulfamethoxazole (SMX) metabolism in human APC (peripheral blood mononuclear cells, Epstein-Barr virus-modified B lymphocytes, monocyte-derived dendritic cells, and two cell lines). APC were incubated with SMX (100 microM-2 mM; 5 min-24 h), in the presence of pathological factors: bacterial endotoxins (lipopolysaccharide and staphylococcal enterotoxin B), flu viral proteins, cytokines [interleukin (IL)-1beta, IL-6, IL-10; tumor necrosis factor-alpha; interferon-gamma; and transforming growth factor-beta], inflammatory molecules (prostaglandin E2, human serum complement, and activated protein C), oxidants (buthionine sulfoximine and H(2)O(2)), and hyperthermia (37.5-39.5 degrees C). Adduct formation was evaluated by enzyme-linked immunosorbent assay and confocal microscopy. SMX-protein adduct formation was time- and concentration-dependent for each cell type tested, in both physiological and danger conditions. A danger environment significantly increased the formation of SMX-protein adducts and significantly shortened the delay for their detection. An additive effect was observed with a combination of danger signals. Dimedone (chemical selectively binding cysteine sulfenic acid) and antioxidants decreased both baseline and danger-enhanced SMX-adduct formation. Various enzyme inhibitors were associated with a significant decrease in SMX-adduct levels, with a pattern varying depending on the cell type and the culture conditions. These results illustrate that danger signals enhance the formation of intracellular SMX-protein adducts in human APC. These findings might be relevant

  5. Detection of human butyrylcholinesterase-nerve gas adducts by liquid chromatography-mass spectrometric analysis after in gel chymotryptic digestion.

    Science.gov (United States)

    Tsuge, Kouichiro; Seto, Yasuo

    2006-06-21

    To verify the exposure to nerve gas, a method for detecting human butyrylcholinesterase (BuChE)-nerve gas adduct was developed using LC-electrospray mass spectrometry (ESI-MS). Purified human serum BuChE was incubated with sarin, soman or VX, and the adduct was purified by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and digested in gel by treatment with chymotrypsin. The resulting peptide mixture was subjected to LC-ESI-MS. From the chymotryptic digest of untreated human BuChE, one peak corresponding to the peptide fragment containing the active center serine residue was detected on the extracted ion chromatogram at m/z 948.5, and the sequence was ascertained to be "GESAGAASVSL" by MS/MS analysis. From the chymotryptic digest of the human BuChE-sarin adduct, a singly charged peptide peak was detected on the extracted ion chromatogram at m/z 1,069.5, and the sequence was ascertained to be "GEXAGAASVSL" by MS/MS analysis (X denotes isopropylmethylphosphonylated serine). The difference in molecular weight (120.0 Da) between the active center peptide fragments corresponding to the untreated BuChE and BuChE-sarin adduct was assumed to be derived from the addition of an isopropyl methylphosphonyl moiety to the serine residue. The formation of human BuChE adducts with soman, VX and an aged soman adduct was confirmed by detecting the respective active center peptide fragments using LC-ESI-MS. To apply the established method to an actual biological sample, human serum was incubated with VX, and the adduct was purified by procainamide affinity chromatography followed by SDS-PAGE. After chymotryptic in gel digestion, the ethylphosphonylated active center peptide fragment could be detected, and the structure of the residue was ascertained by LC-ESI-MS analysis.

  6. Contributions of aryl hydrocarbon receptor genetic variants to the risk of glioma and PAH-DNA adducts.

    Science.gov (United States)

    Gu, Aihua; Ji, Guixiang; Jiang, Tao; Lu, Ailin; You, Yongping; Liu, Ning; Luo, Chengzhang; Yan, Wei; Zhao, Peng

    2012-08-01

    The aryl hydrocarbon receptor (AHR) gene is involved in the response to polycyclic aromatic hydrocarbon (PAH) exposure. To investigate the hypothesis that the genetic variants in the AHR gene might be a causal genetic susceptibility to PAH-DNA adduct formation and glioma risk, we conducted a case-control study of 384 glioma cases and 384 cancer-free controls to explore the association between six common single-nucleotide polymorphisms of the AHR gene and glioma risk. Using PAH-DNA adducts as biomarkers, we then evaluated the association between PAH-DNA adduct levels and glioma risk based on a tissue microarray including 11 controls and 77 glioma patients. We further explored the contributions of the glioma risk-associated AHR polymorphisms to the levels of PAH-DNA adducts in glioma tissues based on 77 glioma patients. We found that PAH-DNA adduct staining existed in normal brain tissues and grades I-IV gliomas, and the staining intensity was significantly associated with the glioma grade. Two AHR polymorphisms (rs2066853 and rs2158041) demonstrated significant association with glioma risk. Intriguingly, we also found statistically significant associations between these two variants and PAH-DNA adduct levels in glioma tissue. These data suggest the contributions of AHR rs2066853 and rs2158041 to glioma risk and the PAH-DNA adduct levels, which shed new light on gene-environment interactions in the etiology of glioma. Further studies with a larger sample size and ethnically diverse populations are required to elucidate the potential biological mechanism for, as well as the impact of, the susceptibility to glioma due to genetic variants of AHR.

  7. Organocatalytic Removal of Formaldehyde Adducts from RNA and DNA Bases

    OpenAIRE

    2015-01-01

    Formaldehyde is universally employed to fix tissue specimens, where it forms hemiaminal and aminal adducts with biomolecules, hindering the ability to retrieve molecular information. Common methods for removing these adducts involve extended heating, which can cause extensive degradation of nucleic acids, particularly RNA. Here we show that water-soluble bifunctional catalysts (anthranilates and phosphanilates) speed the reversal of formaldehyde adducts of mononucleotides over standard buffer...

  8. Plasma effects in electromagnetic field interaction with biological tissue

    Science.gov (United States)

    Sharma, R. P.; Batra, Karuna; Excell, Peter S.

    2011-02-01

    Theoretical analysis is presented of the nonlinear behavior of charge carriers in biological tissue under the influence of varying low-intensity electromagnetic (EM) field. The interaction occurs because of the nonlinear force arising due to the gradient of the EM field intensity acting on free electrons in the conduction band of proteins in metabolically active biological cell membrane receptors leading to a redistribution of charge carriers. Field dependence of the resulting dielectric constant is investigated by a suitable modification to include an additional electronic contribution term to the three-term Debye model. The exogenous EM field propagating in this nonlinear cellular medium satisfies the nonlinear Schrödinger equation and can be affected significantly. Resulting field effect can be substantially augmented and effective rectification/demodulation can occur. Possible implications of this modification on biological processes in white and grey matter are discussed.

  9. Evidence for phosphorus bonding in phosphorus trichloride-methanol adduct: a matrix isolation infrared and ab initio computational study.

    Science.gov (United States)

    Joshi, Prasad Ramesh; Ramanathan, N; Sundararajan, K; Sankaran, K

    2015-04-09

    The weak interaction between PCl3 and CH3OH was investigated using matrix isolation infrared spectroscopy and ab initio computations. In a nitrogen matrix at low temperature, the noncovalent adduct was generated and characterized using Fourier transform infrared spectroscopy. Computations were performed at B3LYP/6-311++G(d,p), B3LYP/aug-cc-pVDZ, and MP2/6-311++G(d,p) levels of theory to optimize the possible geometries of PCl3-CH3OH adducts. Computations revealed two minima on the potential energy surface, of which, the global minimum is stabilized by a noncovalent P···O interaction, known as a pnictogen bonding (phosphorus bonding or P-bonding). The local minimum corresponded to a cyclic adduct, stabilized by the conventional hydrogen bonding (Cl···H-O and Cl···H-C interactions). Experimentally, 1:1 P-bonded PCl3-CH3OH adduct in nitrogen matrix was identified, where shifts in the P-Cl modes of PCl3, O-C, and O-H modes of CH3OH submolecules were observed. The observed vibrational frequencies of the P-bonded adduct in a nitrogen matrix agreed well with the computed frequencies. Furthermore, computations also predicted that the P-bonded adduct is stronger than H-bonded adduct by ∼1.56 kcal/mol. Atoms in molecules and natural bond orbital analyses were performed to understand the nature of interactions and effect of charge transfer interaction on the stability of the adducts.

  10. Sterically locked synthetic bilin derivatives and phytochrome Agp1 from Agrobacterium tumefaciens form photoinsensitive Pr- and Pfr-like adducts.

    Science.gov (United States)

    Inomata, Katsuhiko; Hammam, Mostafa A S; Kinoshita, Hideki; Murata, Yasue; Khawn, Htoi; Noack, Steffi; Michael, Norbert; Lamparter, Tilman

    2005-07-01

    Phytochrome photoreceptors undergo reversible photoconversion between the red-absorbing form, Pr, and the far-red-absorbing form, Pfr. The first step in the conversion from Pr to Pfr is a Z to E isomerization around the C15=C16 double bond of the bilin chromophore. We prepared four synthetic biliverdin (BV) derivatives in which rings C and D are sterically locked by cyclizing with an additional carbon chain. In these chromophores, which are termed 15Za, 15Zs, 15Ea, and 15Es, the C15=C16 double bond is in either the Z or E configuration and the C14-C15 single bond in either the syn or anti conformation. The chromophores were assembled with Agrobacterium phytochrome Agp1, which incorporates BV as natural chromophore. All locked BV derivatives bound covalently to the protein and formed adducts with characteristic spectral properties. The 15Za adduct was spectrally similar to the Pr form and the 15Ea adduct similar to the Pfr form of the BV adduct. Thus, the chromophore of Agp1 adopts a C15=C16 Z configuration and a C14-C15 anti conformation in the Pr form and a C15=C16 E configuration and a C14-C15 anti conformation in the Pfr form. Both the 15Zs and the 15Es adducts absorbed only in the blue region of the visible spectra. All chromophore adducts were analyzed by size exclusion chromatography and histidine kinase activity to probe for protein conformation. In either case, the 15Za adduct behaved like the Pr and the 15Ea adduct like the Pfr form of Agp1. Replacing the natural chromophore by a locked 15Ea derivative can thus bring phytochrome holoprotein in the Pfr form in darkness. In this way, physiological action of Pfr can be studied in vivo and separated from Pr/Pfr cycling and other light effects.

  11. Development of a strategy for biological monitoring in a chemical plant producing 3,3'-dichlorobenzidine dihydrochloride.

    Science.gov (United States)

    Knoell, Kristian F; Will, Norbert; Leng, Gabriele; Selinski, Silvia; Hengstler, Jan G; Golka, Klaus; Bolt, Hermann M

    2012-01-01

    In a chemical plant in Germany producing 3,3'-dichlorobenzidine dihydrochloride for the manufacture of colorants, blood and urine samples were taken for biological monitoring. 3,3'-Dichlorobenzidine (DBZ) was analyzed in urine by thin-layer chromatography and subsequently further combined with analysis of adducts of 3,3'-DBZ in hemoglobin. Data highlight current ranges of industrial exposure to 3,3'-DBZ in Germany and demonstrate the applicability of biological monitoring to minimize this exposure. Effective biological monitoring was achieved by a combination of monitoring hemoglobin adducts with spot samplings of urinary 3,3'-DBZ excretion in cases of reported exposure periods. Data presented might help to identify biological guidance values (BGV/BAR) for 3,3'-DBZ-exposed individuals.

  12. Challenges in Analyzing the Biological Effects of Resveratrol

    DEFF Research Database (Denmark)

    Erdogan, Cihan Süleyman; Vang, Ole

    2016-01-01

    The suggested health effects (e.g., disease prevention) of dietary bioactive compounds such as resveratrol are challenging to prove in comparison to man-made drugs developed for therapeutic purposes. Dietary bioactive compounds have multiple cellular targets and therefore have a variety of biolog...

  13. Adaptation hypothesis of biological effectiveness of ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kudritsky, Yu.K.; Georgievsky, A.B.; Karpov, V.I.

    1993-12-31

    The adoptation hypothesis of biological effectiveness of ionizing radiations is based on the recognition of the invariability of general biological laws for radiobiology and on the comprehension of life evolution regularities and axiomatic principles of environment and biota unity. The ionizing radiation factor is essential for life which could not exist beyond the radiation field. The possibility of future development of the adaptation hypothesis serves as a basis for it`s transformation into the theoretical foundation of radiobiology. This report discusses the aspects of the adaptation theory.

  14. Effect of biologic agents on radiographic progression of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Gabriel J Tobón

    2010-08-01

    Full Text Available Gabriel J Tobón1, Alain Saraux1,2, Valérie Devauchelle-Pensec1,21Immunology Laboratory, Morvan Hospital, Université de Bretagne Occidentale, Brest, France; 2Rheumatology Unit, Hôpital de la Cavale Blanche, CHU Brest, FranceAbstract: The treatment of rheumatoid arthritis (RA has benefited over the last few years from the introduction of biologic agents whose development was based on new insights into the immunological factors involved in the pathogenesis of RA and the development of joint damage. These biological agents have been proven effective in RA patients with inadequate responses to synthetic disease-modifying antirheumatic drugs (DMARDs. Preventing joint damage is now the primary goal of RA treatment, and guidelines exist for the follow-up of joint abnormalities. Most biologic agents produced high clinical and radiological response rates in patients with established or recent-onset RA. Thus, for the first time, obtaining a remission is a reasonable treatment goal in RA patients. Factors that are crucial to joint damage control are: early initiation of DMARDs, use of intensive treatments including biological agents, and close monitoring of clinical disease activity and radiographic progression. However, some patients remain unresponsive to all available treatments and continue to experience joint damage progression. A major objective now is to identify patients at high risk for severe joint damage, in order to tailor the treatment regimen to their specific needs.Keywords: rheumatoid arthritis, radiographic progression, biologics

  15. Predictive modeling of nanomaterial exposure effects in biological systems

    Directory of Open Access Journals (Sweden)

    Liu X

    2013-09-01

    Full Text Available Xiong Liu,1 Kaizhi Tang,1 Stacey Harper,2 Bryan Harper,2 Jeffery A Steevens,3 Roger Xu1 1Intelligent Automation, Inc., Rockville, MD, USA; 2Department of Environmental and Molecular Toxicology, School of Chemical, Biological, and Environmental Engineering, Oregon State University, Corvallis, OR, USA; 3ERDC Environmental Laboratory, Vicksburg, MS, USA Background: Predictive modeling of the biological effects of nanomaterials is critical for industry and policymakers to assess the potential hazards resulting from the application of engineered nanomaterials. Methods: We generated an experimental dataset on the toxic effects experienced by embryonic zebrafish due to exposure to nanomaterials. Several nanomaterials were studied, such as metal nanoparticles, dendrimer, metal oxide, and polymeric materials. The embryonic zebrafish metric (EZ Metric was used as a screening-level measurement representative of adverse effects. Using the dataset, we developed a data mining approach to model the toxic endpoints and the overall biological impact of nanomaterials. Data mining techniques, such as numerical prediction, can assist analysts in developing risk assessment models for nanomaterials. Results: We found several important attributes that contribute to the 24 hours post-fertilization (hpf mortality, such as dosage concentration, shell composition, and surface charge. These findings concur with previous studies on nanomaterial toxicity using embryonic zebrafish. We conducted case studies on modeling the overall effect/impact of nanomaterials and the specific toxic endpoints such as mortality, delayed development, and morphological malformations. The results show that we can achieve high prediction accuracy for certain biological effects, such as 24 hpf mortality, 120 hpf mortality, and 120 hpf heart malformation. The results also show that the weighting scheme for individual biological effects has a significant influence on modeling the overall impact of

  16. Metabolic stability of superoxide and hydroxyl radical adducts of a cyclic nitrone toward rat liver microsomes and cytosol: A stopped-flow ESR spectroscopy study.

    Science.gov (United States)

    Bézière, Nicolas; Frapart, Yves; Rockenbauer, Antal; Boucher, Jean-Luc; Mansuy, Daniel; Peyrot, Fabienne

    2010-08-01

    The metabolic stability of the spin adducts derived from the reaction of superoxide and hydroxyl radicals with 5-tert-butoxycarbonyl-5-methyl-1-pyrroline N-oxide (BocMPO) in the presence of rat liver microsomes (RLM) and rat liver cytosol (RLC) was studied by using a stopped-flow device coupled to an electron spin resonance (ESR) spectrometer. The kinetics of the disappearance of the BocMPO-OH and BocMPO-OOH radicals could be followed by ESR spectroscopy with treatment of the ESR data by an appropriate computer program. The presence of cytosol led to a 60-fold decrease of the half-life of BocMPO-OOH with the intermediate formation of BocMPO-OH. This effect of cytosol was due to an ascorbate- and thiol-dependent reduction of BocMPO-OOH. RLC only led to a 5-fold decrease of the half-life of BocMPO-OH that was predominantly due to cytosolic ascorbate. RLM led to a 10-fold decrease of the BocMPO-OOH half-life that was mainly related to a direct reaction of the hydroperoxide function of BocMPO-OOH with cytochrome P450 Fe(III) (P450). Other ferric heme proteins, such as methemoglobin (metHb) and horseradish peroxidase (HRP), as well as hemin itself, exhibited a similar behavior. RLM and metHb showed a much weaker effect on BocMPO-OH half-life (2-fold decrease), whereas RLM in the presence of NADPH caused a greater decrease of the BocMPO-OH half-life ( approximately 5-fold). The effect of RLM without NADPH was mainly due to a direct reaction with microsomal P450, whereas the RLM- and NADPH-dependent effect was mainly due to flavin-containing reductases such as cytochrome P450 reductase. These data on the effects of liver subcellular fractions on the half-life of the BocMPO-OOH and the BocMPO-OH spin adducts highlight the role of heme as a biological cofactor involved in the disappearance of such spin adducts. They should be helpful for the design of new spin traps that would form more metabolically stable spin adducts in vitro and in vivo.

  17. Fluorescence of Phytochrome Adducts with Synthetic Locked Chromophores*

    Science.gov (United States)

    Zienicke, Benjamin; Chen, Li-Yi; Khawn, Htoi; Hammam, Mostafa A. S.; Kinoshita, Hideki; Reichert, Johannes; Ulrich, Anne S.; Inomata, Katsuhiko; Lamparter, Tilman

    2011-01-01

    We performed steady state fluorescence measurements with phytochromes Agp1 and Agp2 of Agrobacterium tumefaciens and three mutants in which photoconversion is inhibited. These proteins were assembled with the natural chromophore biliverdin (BV), with phycoerythrobilin (PEB), which lacks a double bond in the ring C-D-connecting methine bridge, and with synthetic bilin derivatives in which the ring C-D-connecting methine bridge is locked. All PEB and locked chromophore adducts are photoinactive. According to fluorescence quantum yields, the adducts may be divided into four different groups: wild type BV adducts exhibiting a weak fluorescence, mutant BV adducts with about 10-fold enhanced fluorescence, adducts with locked chromophores in which the fluorescence quantum yields are around 0.02, and PEB adducts with a high quantum yield of around 0.5. Thus, the strong fluorescence of the PEB adducts is not reached by the locked chromophore adducts, although the photoconversion energy dissipation pathway is blocked. We therefore suggest that ring D of the bilin chromophore, which contributes to the extended π-electron system of the locked chromophores, provides an energy dissipation pathway that is independent on photoconversion. PMID:21071442

  18. Fluorescence of phytochrome adducts with synthetic locked chromophores.

    Science.gov (United States)

    Zienicke, Benjamin; Chen, Li-Yi; Khawn, Htoi; Hammam, Mostafa A S; Kinoshita, Hideki; Reichert, Johannes; Ulrich, Anne S; Inomata, Katsuhiko; Lamparter, Tilman

    2011-01-14

    We performed steady state fluorescence measurements with phytochromes Agp1 and Agp2 of Agrobacterium tumefaciens and three mutants in which photoconversion is inhibited. These proteins were assembled with the natural chromophore biliverdin (BV), with phycoerythrobilin (PEB), which lacks a double bond in the ring C-D-connecting methine bridge, and with synthetic bilin derivatives in which the ring C-D-connecting methine bridge is locked. All PEB and locked chromophore adducts are photoinactive. According to fluorescence quantum yields, the adducts may be divided into four different groups: wild type BV adducts exhibiting a weak fluorescence, mutant BV adducts with about 10-fold enhanced fluorescence, adducts with locked chromophores in which the fluorescence quantum yields are around 0.02, and PEB adducts with a high quantum yield of around 0.5. Thus, the strong fluorescence of the PEB adducts is not reached by the locked chromophore adducts, although the photoconversion energy dissipation pathway is blocked. We therefore suggest that ring D of the bilin chromophore, which contributes to the extended π-electron system of the locked chromophores, provides an energy dissipation pathway that is independent on photoconversion.

  19. A liquid-crystalline hexa-adduct of [60]fullerene

    OpenAIRE

    Chuard, Thierry; Deschenaux, Robert; Hirsch, Andreas; Schönberger, Hubert

    2006-01-01

    A hexa-adduct of [60]fullerene was synthesized by addition of a mesomorphic twin cyanobiphenyl malonate derivative to C60; whereas the malonate derivative gave a monotropic nematic phase, the fullerene hexa-adduct showed an enantiotropic smectic A phase.

  20. 18. Adduct detection in human monitoring for carcinogen exposure

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Determination of the covalently bound products (adducts) of carcinogens with DNA or proteins may be used for the monitoring of exposure to these compounds. Protein adducts are generally stable and are not enzymatically repaired, and the use of these for cxposure monitoring is normally carried out with globin or albumin, because

  1. Synthesis and Photophysical Properties of C60-carbazole Adducts

    Institute of Scientific and Technical Information of China (English)

    YIN ,Gui(尹桂); YIN,Gui; MAO,Xin-Ping(毛新平); MAO,Xin-Ping; SUO,Zhi-Yong(锁志勇); SUO,Zhi-Yong; XU,Zheng(徐正); XU,Zheng

    2001-01-01

    Three C60-cartazole adducts have been synthesized by 1,3-dipolar cycloaddition reaction.Intramolecular energy/electron transfer from carbazole to C60 was observed by steady-state absorption and fluorescence spectra.The fluorescence spectra of these adducts were similau to each other and dependent on the excitation wavelength and solvent.

  2. A Review of Depleted Uranium Biological Effects: In vivo Studies

    Science.gov (United States)

    2010-11-01

    Chromatid Exchange Other Biomarkers DNA Adducts Micronuclei Dicentrics Simple: 1 or 2 breaks in 1 chromosome Complex: 3 or more breaks in 2 or more... Chromosomal Aberrations Control 0.25 0.03 DU 0.49 0.05 Ta 0.29 0.03 DU Genotoxicity in vivo (Sprague-Dawley Rats) Miller et al, 2003, Mil Med. 2002 Feb;167(2...Inhalation Internal Fragment Unpublished data Comparison of Inhalation versus Chronic Internal Fragment Exposure in vivo: Measurement of Chromosomal

  3. Biological effects of exposure to magnetic resonance imaging: an overview

    Directory of Open Access Journals (Sweden)

    Formica Domenico

    2004-04-01

    Full Text Available Abstract The literature on biological effects of magnetic and electromagnetic fields commonly utilized in magnetic resonance imaging systems is surveyed here. After an introduction on the basic principles of magnetic resonance imaging and the electric and magnetic properties of biological tissues, the basic phenomena to understand the bio-effects are described in classical terms. Values of field strengths and frequencies commonly utilized in these diagnostic systems are reported in order to allow the integration of the specific literature on the bio-effects produced by magnetic resonance systems with the vast literature concerning the bio-effects produced by electromagnetic fields. This work gives an overview of the findings about the safety concerns of exposure to static magnetic fields, radio-frequency fields, and time varying magnetic field gradients, focusing primarily on the physics of the interactions between these electromagnetic fields and biological matter. The scientific literature is summarized, integrated, and critically analyzed with the help of authoritative reviews by recognized experts, international safety guidelines are also cited.

  4. Diet-related DNA adduct formation in relation to carcinogenesis.

    Science.gov (United States)

    Hemeryck, Lieselot Y; Vanhaecke, Lynn

    2016-08-01

    The human diet contributes significantly to the initiation and promotion of carcinogenesis. It has become clear that the human diet contains several groups of natural foodborne chemicals that are at least in part responsible for the genotoxic, mutagenic, and carcinogenic potential of certain foodstuffs. Electrophilic chemicals are prone to attack nucleophilic sites in DNA, resulting in the formation of altered nucleobases, also known as DNA adducts. Since DNA adduct formation is believed to signal the onset of chemically induced carcinogenesis, the DNA adduct-inducing potential of certain foodstuffs has been investigated to gain more insight into diet-related pathways of carcinogenesis. Many studies have investigated diet-related DNA adduct formation. This review summarizes work on known or suspected dietary carcinogens and the role of DNA adduct formation in hypothesized carcinogenesis pathways.

  5. Quantum Chemical Studies on Detail Mechanism of Nitrosylation of NAMI-A-HSA Adduct.

    Science.gov (United States)

    Das, Dharitri; Mondal, Paritosh

    2015-08-20

    Hydrolysis of NAMI-A in NAMI-A-HSA (HSA = human serum albumin) and nitrosylation of hydrolyzed NAMI-A-HSA adduct have been studied in detail using density functional theory method. It has been observed that the chloride exchange reaction with water in the NAMI-A-HSA adduct follows an interchange dissociative mechanism passing through an unstable heptacoordinated activated complex. The computed free energy of activation (ΔG) and rate constant (k) for the hydrolysis process in aqueous medium are observed to be 24.85 kcal mol(-1) and 3.81 × 10(-6) s(-1), respectively. Nitrosylation of hydrolyzed NAMI-A-HSA adduct with nitric oxide is found to be thermodynamically more favorable with the incorporation of solvent effect and provides a detailed understanding related to the antimetastatic activity of the NAMI-A drug. This investigation shows that nitric oxide coordinates linearly to NAMI-A-HSA adduct leading to the reduction of ruthenium(III) to more active ruthenium(II), with the reduction potential of -2.32 V. Negative relative solvation and relative binding free energies suggest that the hydrolysis and nitrosylation reactions are found to be thermodynamically favorable and faster. Our computed results provide a detailed thermodynamics and kinetics which may be highly beneficial for understanding antimetastatic activity as well as the nitric oxide scavenging ability of NAMI-A.

  6. The N(2)-Furfuryl-deoxyguanosine Adduct Does Not Alter the Structure of B-DNA.

    Science.gov (United States)

    Ghodke, Pratibha P; Gore, Kiran R; Harikrishna, S; Samanta, Biswajit; Kottur, Jithesh; Nair, Deepak T; Pradeepkumar, P I

    2016-01-15

    N(2)-Furfuryl-deoxyguanosine (fdG) is carcinogenic DNA adduct that originates from furfuryl alcohol. It is also a stable structural mimic of the damage induced by the nitrofurazone family of antibiotics. For the structural and functional studies of this model N(2)-dG adduct, reliable and rapid access to fdG-modified DNAs are warranted. Toward this end, here we report the synthesis of fdG-modified DNAs using phosphoramidite chemistry involving only three steps. The functional integrity of the modified DNA has been verified by primer extension studies with DNA polymerases I and IV from E. coli. Introduction of fdG into a DNA duplex decreases the Tm by ∼1.6 °C/modification. Molecular dynamics simulations of a DNA duplex bearing the fdG adduct revealed that though the overall B-DNA structure is maintained, this lesion can disrupt W-C H-bonding, stacking interactions, and minor groove hydrations to some extent at the modified site, and these effects lead to slight variations in the local base pair parameters. Overall, our studies show that fdG is tolerated at the minor groove of the DNA to a better extent compared with other bulky DNA damages, and this property will make it difficult for the DNA repair pathways to detect this adduct.

  7. Oral Cell DNA Adducts as Potential Biomarkers for Lung Cancer Susceptibility in Cigarette Smokers

    Science.gov (United States)

    Hecht, Stephen S.

    2017-01-01

    This perspective considers the use of oral cell DNA adducts, together with exposure and genetic information, to potentially identify those cigarette smokers at highest risk for lung cancer, so that appropriate preventive measures could be initiated at a relatively young age before too much damage has been done. There are now well established and validated analytical methods for the quantitation of urinary and serum metabolites of tobacco smoke toxicants and carcinogens. These metabolites provide a profile of exposure and in some cases lung cancer risk. But they do not yield information on the critical DNA damage parameter that leads to mutations in cancer growth control genes such as KRAS and TP53. Studies demonstrate a correlation between changes in the oral cavity and lung in cigarette smokers, due to the field effect of tobacco smoke. Oral cell DNA is readily obtained in contrast to DNA samples from the lung. Studies in which oral cell DNA and salivary DNA have been analyzed for specific DNA adducts are reviewed; some of the adducts identified have also been previously reported in lung DNA from smokers. The multiple challenges of developing a panel of oral cell DNA adducts that could be routinely quantified by mass spectrometry are discussed. PMID:28092948

  8. Adduct formation of ionic and nanoparticular silver with amino acids and glutathione

    Energy Technology Data Exchange (ETDEWEB)

    Blaske, Franziska; Stork, Lisa; Sperling, Michael; Karst, Uwe, E-mail: uk@uni-muenster.de [University of Muenster, Institute of Inorganic and Analytical Chemistry (Germany)

    2013-09-15

    To investigate the interaction of ionic and nanoparticular silver with amino acids and small peptides, an electrospray ionization time-of-flight mass spectrometry method was developed. Monomeric and oligomeric silver adducts were formed with amino acids including cysteine (Cys), methionine, histidine, lysine, or the tripeptide glutathione (GSH). The obtained spectra for ionic silver show clusters in different ratios between Ag{sup +} and the reaction partners (X) including [Ag{sub n}X{sub m} - (n + 1)H]{sup -} (n = 1-4, m = 1-3). Regarding Cys, adduct clusters up to n = 5 and m = 4 were observed as well. Considering silver-GSH interactions, even doubly charged oligomers occur generating [Ag{sub (a+1)}GSH{sub a} - (a + 3)H]{sup 2-} (a = 5-7) and [Ag{sub b}GSH{sub b} - (b + 2)H]{sup 2-} (b = 4-8) ions. {sup 1}H NMR data of free GSH compared to that after treatment with Ag{sup +} confirm sulfur-metal interactions due to changing chemical shifts for the protons located adjacent to the thiol group. Density functional theory calculations for silver-GSH clusters may explain the formation of experimentally recorded large clusters due to cooperative effects between silver and carboxylic acid side chains. Both sets of experiments indicate the presence of these adducts in the liquid phase. For silver nanoparticles, the respective data confirm the release of silver ions and the subsequent adduct formation.

  9. Advances in the biological effects of terahertz wave radiation.

    Science.gov (United States)

    Zhao, Li; Hao, Yan-Hui; Peng, Rui-Yun

    2014-01-01

    The terahertz (THz) band lies between microwave and infrared rays in wavelength and consists of non-ionizing radiation. Both domestic and foreign research institutions, including the army, have attached considerable importance to the research and development of THz technology because this radiation exhibits both photon-like and electron-like properties, which grant it considerable application value and potential. With the rapid development of THz technology and related applications, studies of the biological effects of THz radiation have become a major focus in the field of life sciences. Research in this field has only just begun, both at home and abroad. In this paper, research progress with respect to THz radiation, including its biological effects, mechanisms and methods of protection, will be reviewed.

  10. Advances in the biological effects of terahertz wave radiation

    Institute of Scientific and Technical Information of China (English)

    Li Zhao; Yan-Hui Hao; Rui-Yun Peng

    2014-01-01

    The terahertz (THz) band lies between microwave and infrared rays in wavelength and consists of non-ionizing radiation. Both domestic and foreign research institutions, including the army, have attached considerable importance to the research and development of THz technology because this radiation exhibits both photon-like and electron-like properties, which grant it considerable application value and potential. With the rapid development of THz technology and related applications, studies of the biological effects of THz radiation have become a major focus in the field of life sciences. Research in this field has only just begun, both at home and abroad. In this paper, research progress with respect to THz radiation, including its biological effects, mechanisms and methods of protection, will be reviewed.

  11. Controlling the biological effects of spermine using a synthetic receptor.

    Science.gov (United States)

    Vial, Laurent; Ludlow, R Frederick; Leclaire, Julien; Pérez-Fernandez, Ruth; Otto, Sijbren

    2006-08-09

    Polyamines play an important role in biology, yet their exact function in many processes is poorly understood. Artificial host molecules capable of sequestering polyamines could be useful tools for studying their cellular function. However, designing synthetic receptors with affinities sufficient to compete with biological polyamine receptors remains a huge challenge. Binding affinities of synthetic hosts are typically separated by a gap of several orders of magnitude from those of biomolecules. We now report that a dynamic combinatorial selection approach can deliver a synthetic receptor that bridges this gap. The selected receptor binds spermine with a dissociation constant of 22 nM, sufficient to remove it from its natural host DNA and reverse some of the biological effects of spermine on the nucleic acid. In low concentrations, spermine induces the formation of left-handed DNA, but upon addition of our receptor, the DNA reverts back to its right-handed form. NMR studies and computer simulations suggest that the spermine complex has the form of a pseudo-rotaxane. The spermine receptor is a promising lead for the development of therapeutics or molecular probes for elucidating spermine's role in cell biology.

  12. Effect of pH on biological phosphorus uptake.

    Science.gov (United States)

    Serralta, J; Ferrer, J; Borrás, L; Seco, A

    2006-12-05

    An anaerobic aerobic laboratory scale sequencing batch reactor (SBR) was operated to study the effect of pH on enhanced biological phosphorus removal. Seven steady states were achieved under different operating conditions. In all of them, a slight variation in the pH value was observed during anaerobic phase. However, pH rose significantly during aerobic phase. The increase observed was due to phosphorus uptake and carbon dioxide stripping. When pH was higher than 8.2-8.25 the phosphorus uptake rate clearly decreased. The capability of Activated Sludge Model No. 2d (ASM2d) and Biological Nutrient Removal Model No. 1 (BNRM1) to simulate experimental results was evaluated. Both models successfully characterized the enhanced biological phosphorus removal performance of the SBR. Furthermore, BNRM1 also reproduced the pH variations observed and the decrease in the phosphorus uptake rate. This model includes a switch function in the kinetic expressions to represent the pH inhibition in biological processes. The pH inhibition constants related to polyphosphate storage process were obtained by adjusting model predictions to measured phosphorus concentrations. On the other hand, pH inhibition should be included in ASM2d to accurately simulate experimental phosphorus evolution observed in an A/O SBR.

  13. Effect of Ceramic Scaffold Architectural Parameters on Biological Response

    Directory of Open Access Journals (Sweden)

    Maria Isabella eGariboldi

    2015-10-01

    Full Text Available Numerous studies have focused on the optimization of ceramic architectures to fulfill a variety of scaffold functional requirements and improve biological response. Conventional fabrication techniques, however, do not allow for the production of geometrically controlled, reproducible structures and often fail to allow the independent variation of individual geometric parameters. Current developments in additive manufacturing technologies suggest that 3D printing will allow a more controlled and systematic exploration of scaffold architectures. This more direct translation of design into structure requires a pipeline for design-driven optimization. A theoretical framework for systematic design and evaluation of architectural parameters on biological response is presented. Four levels of architecture are considered, namely (1 surface topography, (2 pore size and geometry, (3 porous networks and (4 macroscopic pore arrangement, including the potential for spatially varied architectures. Studies exploring the effect of various parameters within these levels are reviewed. This framework will hopefully allow uncovering of new relationships between architecture and biological response in a more systematic way, as well as inform future refinement of fabrication techniques to fulfill architectural necessities with a consideration of biological implications.

  14. Effect of Ceramic Scaffold Architectural Parameters on Biological Response.

    Science.gov (United States)

    Gariboldi, Maria Isabella; Best, Serena M

    2015-01-01

    Numerous studies have focused on the optimization of ceramic architectures to fulfill a variety of scaffold functional requirements and improve biological response. Conventional fabrication techniques, however, do not allow for the production of geometrically controlled, reproducible structures and often fail to allow the independent variation of individual geometric parameters. Current developments in additive manufacturing technologies suggest that 3D printing will allow a more controlled and systematic exploration of scaffold architectures. This more direct translation of design into structure requires a pipeline for design-driven optimization. A theoretical framework for systematic design and evaluation of architectural parameters on biological response is presented. Four levels of architecture are considered, namely (1) surface topography, (2) pore size and geometry, (3) porous networks, and (4) macroscopic pore arrangement, including the potential for spatially varied architectures. Studies exploring the effect of various parameters within these levels are reviewed. This framework will hopefully allow uncovering of new relationships between architecture and biological response in a more systematic way as well as inform future refinement of fabrication techniques to fulfill architectural necessities with a consideration of biological implications.

  15. The knee adduction moment during gait is associated with the adduction angle measured during computer-assisted total knee arthroplasty.

    Science.gov (United States)

    Roda, Richard D; Wilson, Janie L Astephen; Wilson, David A J; Richardson, Glen; Dunbar, Michael J

    2012-06-01

    Computer-assisted surgery can be used to measure 3-dimensional knee function during arthroplasty surgery; however, it is unknown if the movement of the knee measured during surgery is related to the in vitro, dynamic state of the knee joint, specifically the knee adduction moment during gait, which has been related to implant migration. The purpose of this study was to determine if the preoperative adduction moment is correlated with the knee abduction/adduction angle measured intraoperatively. A statistically significant correlation was found between the mean (r(2) = 0.59; P = .001) and peak (r(2) = 0.53; P = .003) preoperative knee adduction moment and the mean abduction/adduction angle measured intraoperatively. The association found in this study suggests the potential for incorporating functional information that relates to surgical outcome into surgical decision making using computer-assisted surgery.

  16. Intuitive biological thought: Developmental changes and effects of biology education in late adolescence.

    Science.gov (United States)

    Coley, John D; Arenson, Melanie; Xu, Yian; Tanner, Kimberly D

    2017-02-01

    A large body of cognitive research has shown that people intuitively and effortlessly reason about the biological world in complex and systematic ways. We addressed two questions about the nature of intuitive biological reasoning: How does intuitive biological thinking change during adolescence and early adulthood? How does increasing biology education influence intuitive biological thinking? To do so, we developed a battery of measures to systematically test three components of intuitive biological thought: anthropocentric thinking, teleological thinking and essentialist thinking, and tested 8th graders and university students (both biology majors, and non-biology majors). Results reveal clear evidence of persistent intuitive reasoning among all populations studied, consistent but surprisingly small differences between 8th graders and college students on measures of intuitive biological thought, and consistent but again surprisingly small influence of increasing biology education on intuitive biological reasoning. Results speak to the persistence of intuitive reasoning, the importance of taking intuitive knowledge into account in science classrooms, and the necessity of interdisciplinary research to advance biology education. Further studies are necessary to investigate how cultural context and continued acquisition of expertise impact intuitive biology thinking.

  17. Biological effects from electromagnetic field exposure and public exposure standards.

    Science.gov (United States)

    Hardell, Lennart; Sage, Cindy

    2008-02-01

    During recent years there has been increasing public concern on potential health risks from power-frequency fields (extremely low frequency electromagnetic fields; ELF) and from radiofrequency/microwave radiation emissions (RF) from wireless communications. Non-thermal (low-intensity) biological effects have not been considered for regulation of microwave exposure, although numerous scientific reports indicate such effects. The BioInitiative Report is based on an international research and public policy initiative to give an overview of what is known of biological effects that occur at low-intensity electromagnetic fields (EMFs) exposure. Health endpoints reported to be associated with ELF and/or RF include childhood leukaemia, brain tumours, genotoxic effects, neurological effects and neurodegenerative diseases, immune system deregulation, allergic and inflammatory responses, breast cancer, miscarriage and some cardiovascular effects. The BioInitiative Report concluded that a reasonable suspicion of risk exists based on clear evidence of bioeffects at environmentally relevant levels, which, with prolonged exposures may reasonably be presumed to result in health impacts. Regarding ELF a new lower public safety limit for habitable space adjacent to all new or upgraded power lines and for all other new constructions should be applied. A new lower limit should also be used for existing habitable space for children and/or women who are pregnant. A precautionary limit should be adopted for outdoor, cumulative RF exposure and for cumulative indoor RF fields with considerably lower limits than existing guidelines, see the BioInitiative Report. The current guidelines for the US and European microwave exposure from mobile phones, for the brain are 1.6 W/Kg and 2 W/Kg, respectively. Since use of mobile phones is associated with an increased risk for brain tumour after 10 years, a new biologically based guideline is warranted. Other health impacts associated with exposure to

  18. The use of innate immune responses as biomarkers in a programme of integrated biological effects monitoring on flounder (Platichthys flesus) from the southern North Sea

    Science.gov (United States)

    Skouras, Andreas; Broeg, Katja; Dizer, Halim; von Westernhagen, Hein; Hansen, Peter-Diedrich; Steinhagen, Dieter

    2003-10-01

    Immunological biomarkers that reflect the effects of exposure to environmental contaminants in coastal marine habitats were sought in European flounder (Platichthys flesus) from five locations in the German Bight with different anthropogenic impacts. During a 2-year period of sampling, innate immune responses were monitored from a total of 331 individual flounder of a body length of 18 to 25 cm. From the fish, plasma lysozyme, phagocytosis and respiratory burst activity of head kidney leucocytes were analysed and implemented as part of an integrated biological effects monitoring programme. As the measurements of the parameters applied here varied within wide ranges at some locations, spatial differences could not always be established, but some general trends could be drawn: plasma lysozyme activity was decreased in flounder contaminated with DDT adducts and some PCBs, while cellular functions such as phagocytosis and respiratory burst were stimulated by some chlorinated hydrocarbons. Correlation analysis also revealed connections not only between the parameters applied here and some contaminants but also with some biochemical parameters used as biomarkers in pollution monitoring: in flounder with decreased integrity of hepatocyte lysosomal membranes, immune functions also were impaired, and plasma lysozyme as well as phagocytosis activity of head kidney cells were impaired when the activity of cytochrome P450 1A was induced. The data presented here indicate that innate immune responses may be useful parameters to monitor cellular functions in a battery of biomarkers of different levels of biological organisation.

  19. Redshift or adduct stabilization -- a computational study of hydrogen bonding in adducts of protonated carboxylic acids

    DEFF Research Database (Denmark)

    Olesen, Solveig Gaarn; Hammerum, Steen

    2009-01-01

    not always yield consistent predictions, as illustrated by the hydrogen bonds formed by the E and Z OH groups of protonated carboxylic acids. The delta-PA and the stabilization of a series of hydrogen bonded adducts indicate that the E OH group forms the stronger hydrogen bonds, whereas the bond length...... carboxylic acids are different. The OH bond length and IR redshift afford the better measure of hydrogen bond strength....

  20. Biological effects of low level exposures to chemicals and radiation

    Energy Technology Data Exchange (ETDEWEB)

    Calabrese, E.J. (ed.)

    1992-01-01

    In May 1990 a group of scientists representing several federal agencies, the International Society of Regulatory Toxicology and Pharmacology, the private sector, and academia met to develop a strategy to encourage the study of the biological effects of low level exposures (BELLE) to chemical agents and radioactivity. A workshop was held in 1991 with seven invited speakers focusing on the toxicological implications of biological adaptations. The selection of topics and speakers was designed to consider critically the concept of hormesis, not only in a broad, conceptual manner, but also at the molecular and biochemical levels. These presentations offered a complementary perspective on the diverse range of molecular mechanisms that can become activated at low levels of toxicant exposure. In addition to chemical toxicology research, an overview of current research on Effects of low-dose radiation on the immune response' was presented as well as Cellular adaptation as an important response during chemical carcinogenesis'. The final presentation was devoted to biostatistical considerations when designing studies that address issues associated with the biological responses to low doses of chemicals and radiation, as well as issues in interpretation of the findings from such studies.

  1. 1,N(2)-propanodeoxyguanosine adduct formation in aortic DNA following inhalation of acrolein.

    Science.gov (United States)

    Penn, A; Nath, R; Pan, J; Chen, L; Widmer, K; Henk, W; Chung, F L

    2001-03-01

    Recent reports indicate that many of the cytotoxic and health-threatening components of environmental tobacco smoke (ETS) reside in the vapor phase of the smoke. We have reported previously that inhalation of 1,3-butadiene, a prominent vapor phase component of ETS, accelerates arteriosclerotic plaque development in cockerels. In this study we asked whether inhaled acrolein, a reactive aldehyde that is also a prominent vapor-phase component of ETS, damages artery-wall DNA and accelerates plaque development. Cockerels inhaled 0, 1, or 10 ppm acrolein mixed with HEPA-filtered air for 6 hr. Half were killed immediately (day 1 group) for detection of the stable, premutagenic 1,N(2)-propanodeoxyguanosine acrolein adduct (AdG3) in aortic DNA via a (32)P-postlabeling/HPLC method, and half were killed after 10 days (day 10 group) for indirect assessment of adduct repair. In the day 1 group, acrolein-DNA adducts were 5 times higher in the 1 and 10 ppm groups than in HEPA-filtered air controls. However, in the day 10 group, adduct levels in the 1 and 10 ppm acrolein groups were reduced to the control adduct level. For the plaque studies, cockerels inhaled 1 ppm acrolein (6 hr/day, 8 weeks), mixed with the same HEPA-filtered air inhaled by controls. Plaque development was measured blind by computerized morphometry. Unlike butadiene inhalation, acrolein inhalation did not accelerate plaque development. Thus, even though repeated exposure to acrolein alone has no effect on plaque size under the exposure conditions described here, a single, brief inhalation exposure to acrolein elicits repairable DNA damage to the artery wall. These results suggest that frequent exposure to ETS may lead to persistent artery-wall DNA damage and thus provide sites on which other ETS plaque accelerants can act.

  2. Covalent adduct formation between the plasmalogen-derived modification product 2-chlorohexadecanal and phloretin.

    Science.gov (United States)

    Üllen, Andreas; Nusshold, Christoph; Glasnov, Toma; Saf, Robert; Cantillo, David; Eibinger, Gerald; Reicher, Helga; Fauler, Günter; Bernhart, Eva; Hallstrom, Seth; Kogelnik, Nora; Zangger, Klaus; Oliver Kappe, C; Malle, Ernst; Sattler, Wolfgang

    2015-02-15

    Hypochlorous acid added as reagent or generated by the myeloperoxidase (MPO)-H2O2-Cl(-) system oxidatively modifies brain ether-phospholipids (plasmalogens). This reaction generates a sn2-acyl-lysophospholipid and chlorinated fatty aldehydes. 2-Chlorohexadecanal (2-ClHDA), a prototypic member of chlorinated long-chain fatty aldehydes, has potent neurotoxic potential by inflicting blood-brain barrier (BBB) damage. During earlier studies we could show that the dihydrochalcone-type polyphenol phloretin attenuated 2-ClHDA-induced BBB dysfunction. To clarify the underlying mechanism(s) we now investigated the possibility of covalent adduct formation between 2-ClHDA and phloretin. Coincubation of 2-ClHDA and phloretin in phosphatidylcholine liposomes revealed a half-life of 2-ClHDA of approx. 120min, decaying at a rate of 5.9×10(-3)min(-1). NMR studies and enthalpy calculations suggested that 2-ClHDA-phloretin adduct formation occurs via electrophilic aromatic substitution followed by hemiacetal formation on the A-ring of phloretin. Adduct characterization by high-resolution mass spectroscopy confirmed these results. In contrast to 2-ClHDA, the covalent 2-ClHDA-phloretin adduct was without adverse effects on MTT reduction (an indicator for metabolic activity), cellular adenine nucleotide content, and barrier function of brain microvascular endothelial cells (BMVEC). Of note, 2-ClHDA-phloretin adduct formation was also observed in BMVEC cultures. Intraperitoneal application and subsequent GC-MS analysis of brain lipid extracts revealed that phloretin is able to penetrate the BBB of C57BL/6J mice. Data of the present study indicate that phloretin scavenges 2-ClHDA, thereby attenuating 2-ClHDA-mediated brain endothelial cell dysfunction. We here identify a detoxification pathway for a prototypic chlorinated fatty aldehyde (generated via the MPO axis) that compromises BBB function in vitro and in vivo.

  3. Non Covalent Interactions and Internal Dynamics in Adducts of Freons

    Science.gov (United States)

    Caminati, Walther; Gou, Qian; Evangelisti, Luca; Feng, Gang; Spada, Lorenzo; Vallejo-López, Montserrat; Lesarri, Alberto; Cocinero, Emilio J.

    2014-06-01

    The complexation of chlorofluorocarbons (CFCs) with atmospheric water and pollutants of the atmosphere affects their reactivity and it seems to accelerate, for example, the decomposition rate of freons in the atmosphere [1]. For this reason we characterized shapes, stabilities, nature of the non-covalent interactions, structures and internal dynamics of a number of complexes of CFCs with water and of their dimers or oligomers by rotational spectroscopy. It has been found that hydrogenated CFCs form adducts with other molecules through weak hydrogen bonds (WHBs). Their C-H groups can act as proton donors, enhanced by the electron withdrawing of the halogen atoms, interacting with the electron rich regions of the partner molecules [2]. Also in adducts or oligomers of hydrogenated CFCs the monomer units are held together by nets of WHBs [3]. When CFCs are perhalogenated, the positive electrostatic region ("σ-hole") can interact electrostatically with negative sites of another, or of the same molecular entity, giving rise, according to IUPAC, to the so called halogen bond (HaB). However, it has been observed that when the perhalogenated CFCs has a Π electron system, a lone pair•••Π interaction (Bürgi-Dunitz) is favoured [4]. We describe here the HaBs that CF4 and CF3Cl form with a variety of partner molecules such as water, ammonia, dimethyl ether, etc. Important spectroscopic features outline strong dynamics effects taking place in this kind of complex. References [1] V. Vaida, H. G. Kjaergaard, K. J. Feierabend, Int. Rev. Phys. Chem. 22 (2003) 203. [2] See, for example: W. Caminati, S. Melandri, A. Maris, P. Ottaviani, Angew. Chem. Int. Ed. 45 (2006) 2438. [3] G. Feng, L. Evangelisti, I. Cacelli, L. Carbonaro, G. Prampolini, W. Caminati, Chem. Commun. 50 (2014) 171. [4] Q. Gou, G. Feng, L. Evangelisti, W. Caminati, Angew. Chem. Int. Ed. 52 (2013) 52 11888.

  4. Biological effects of pulsating magnetic fields: role of solitons

    CERN Document Server

    Brizhik, Larissa

    2014-01-01

    In this paper, we analyze biological effects produced by magnetic fields in order to elucidate the physical mechanisms, which can produce them. We show that there is a chierarchy of such mechanisms and that the mutual interplay between them can result in the synergetic outcome. In particular, we analyze the biological effects of magnetic fields on soliton mediated charge transport in the redox processes in living organisms. Such solitons are described by nonlinear systems of equations and represent electrons that are self-trapped in alpha-helical polypeptides due to the moderately strong electron-lattice interaction. They represent a particular type of disssipativeless large polarons in low-dimensional systems. We show that the effective mass of solitons in the is different from the mass of free electrons, and that there is a resonant effect of the magnetic fields on the dynamics of solitons, and, hence, on charge transport that accompanies photosynthesis and respiration. These effects can result in non-therm...

  5. Relative biological effectiveness of the boron neutron-capture beam for the inactivation of biological macromolecules

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Masahiro (Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst.)

    1993-12-01

    The r.b.e. values of the boron neutron-capture beam (BNCB) for inactivation of yeast alcohol dehydrogenase (YADH) and the coenzyme NADH were determined in aqueous and air-saturated state. The r.b.e. value for YADH was 0.24 at a protein concentration of 0.2 mg/ml and that for NADH at the same concentration was 0.4. These r.b.e. values are less than unity in contrast to the r.b.e. values of BNCB for cell killing and mutagenesis which usually exceed 2. The small r.b.e. values for biological macromolecules is mainly explained from a relatively low yield of the radical species OH and H produced by high LET radiations compared to low LET radiations. Dithiothreitol protected YADH efficiently against inactivation by BNCB. It was suggested that radical repair process is the major cause of the observed radioprotective effect. (author).

  6. Bulky carcinogen-DNA adducts and exposure to environmental and occupational sources of polycyclic aromatic hydrocarbons. Influence of susceptibility genotypes on adduct level

    Energy Technology Data Exchange (ETDEWEB)

    Sabro Nielsen, P.

    1996-12-31

    PAH exposure, whether it is of occupational or environmental origin, is thought to result in an elevated risk of cancer especially in the lungs. DNA damage is considered an important step in the carcinogenic effect of PAH. Hence, methods that elucidate the steps in the carcinogenic process are important to understand the action of PAH. It may prove useful in the exposure assessment and in combination with classical epidemiological methods give better basis for risk estimation. The objective in this thesis was to evaluate the feasibility of the {sup 32}P-postlabeling method to detect carcinogen-DNA adducts for assessing exposure to DNA damaging compounds in different occupationally and environmentally exposed groups. The studies included groups, that have an elevated cancer risk due to occupational exposure to PAH. Exposure levels were supposed to be relatively low according to reports on occupational and environmental air quality programs. Another aim was to evaluate the influence of polymorphisms in metabolizing enzyme genes on DNA adduct levels. A third objective was to establish some kind of baseline DNA adduct level for individuals with supposed low exposure, and compare it to the more exposed groups. A fourth aim in these studies was to examine if biomarkers of genotoxic exposure could be useful in epidemiological studies to identify groups at risk and thereby contribute with better exposure estimates in the study of PAH related cancer risk. (EG).

  7. DNA adducts, benzo(a)pyrene monooxygenase activity, and lysosomal membrane stability in Mytilus galloprovincialis from different areas in Taranto coastal waters (Italy).

    Science.gov (United States)

    Pisoni, M; Cogotzi, L; Frigeri, A; Corsi, I; Bonacci, S; Iacocca, A; Lancini, L; Mastrototaro, F; Focardi, S; Svelto, M

    2004-10-01

    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 beta-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

  8. The Biological Effects of Ivabradine in Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Graziano Riccioni

    2012-04-01

    Full Text Available A large number of studies in healthy and asymptomatic subjects, as well as patients with already established cardiovascular disease (CAD have demonstrated that heart rate (HR is a very important and major independent cardiovascular risk factor for prognosis. Lowering heart rate reduces cardiac work, thereby diminishing myocardial oxygen demand. Several experimental studies in animals, including dogs and pigs, have clarified the beneficial effects of ivabradine associated with HR lowering. Ivabradine is a selective inhibitor of the hyperpolarisation activated cyclic-nucleotide-gated funny current (If involved in pacemaker generation and responsiveness of the sino-atrial node (SAN, which result in HR reduction with no other apparent direct cardiovascular effects. Several studies show that ivabradine substantially and significantly reduces major risks associated with heart failure when added to guideline-based and evidence-based treatment. However the biological effect of ivabradine have yet to be studied. This effects can appear directly on myocardium or on a systemic level improving endothelial function and modulating immune cell migration. Indeed ivabradine is an ‘open-channel’ blocker of human hyperpolarization-activated cyclic nucleotide gated channels of type-4 (hHCN4, and a ‘closed-channel’ blocker of mouse HCN1 channels in a dose-dependent manner. At endothelial level ivabradine decreased monocyte chemotactin protein-1 mRNA expression and exerted a potent anti-oxidative effect through reduction of vascular NADPH oxidase activity. Finally, on an immune level, ivabradine inhibits the chemokine-induced migration of CD4-positive lymphocytes. In this review, we discuss the biological effects of ivabradine and highlight its effects on CAD.

  9. Hydrodynamic collective effects of active proteins in biological membranes

    CERN Document Server

    Koyano, Yuki; Mikhailov, Alexander S

    2016-01-01

    Lipid bilayers forming biological membranes are known to behave as viscous 2D fluids on submicrometer scales; usually they contain a large number of active protein inclusions. Recently, it has been shown [Proc. Nat. Acad. Sci. USA 112, E3639 (2015)] that such active proteins should in- duce non-thermal fluctuating lipid flows leading to diffusion enhancement and chemotaxis-like drift for passive inclusions in biomembranes. Here, a detailed analytical and numerical investigation of such effects is performed. The attention is focused on the situations when proteins are concentrated within lipid rafts. We demonstrate that passive particles tend to become attracted by active rafts and are accumulated inside them.

  10. Current research on biological effects of low-level exposures

    Energy Technology Data Exchange (ETDEWEB)

    Sagan, L.A.

    1994-12-31

    Rather substantial numbers of industrial chemicals, pharmaceuticals, and radiation display U-shaped or seemingly paradoxical dose-response relationships. A limited listing of studies providing examples of data fitting the U-shaped curve has been published. This array suggests that the U-shaped response is broadly generalizable and therefore potentially of considerable significance in the toxicological and public health domains. In fact, in 1992 and 1993, three conferences (Japan, United States, and China) were held exclusively on the topic of the biological effects of low doses of chemicals and radioactivity with articular emphasis on U-shaped curves. Substantial efforts have been made at understanding this observation.

  11. Biological activity of selected plants with adaptogenic effect

    Directory of Open Access Journals (Sweden)

    Eva Ivanišová

    2016-05-01

    Full Text Available The aim of this study was to determine biological activity of plants with adaptogenic effect: Panax ginseng Mayer., Withania somnifera L., Eleuterococcus senticosus Rupr. et Maxim., Astragallus membranaceus Fisch. and Codonopsis pilosulae Franch. The antioxidant activity was detected by DPPH and phosphomolybdenum method, total polyphenol content with Folin – Ciocalteu reagent, flavonoids content by aluminium chloride method. The detection of antimicrobial activity was carried out by disc diffusion method against three species of Gram-negative bacteria: Escherichia coli CCM 3988, Salmonella enterica subsp. enterica CCM 3807, Yersinia enterocolitica CCM 5671 and two Gram-positive bacteria: Bacillus thuringiensis CCM 19, Stapylococcus aureus subsp. aureus CCM 2461. Results showed that plants with adaptogenic effect are rich for biologically active substances. The highest antioxidant activity by DPPH method was determined in the sample of Eleuterococcus senticosus (3.15 mg TEAC – Trolox equivalent antioxidant capacity per g of sample and by phosphomolybdenum method in the sample of Codonopsis pilosulae (188.79 mg TEAC per g of sample. In the sample of Panax ginseng was measured the highest content of total polyphenols (8.10 mg GAE – galic acid equivalent per g of sample and flavonoids (3.41 μg QE – quercetin equivalent per g of sample. All samples also showed strong antimicrobial activity with the best results in Panax ginseng and Withania somnifera in particular for species Yersinia enterocolitica CCM 5671 and Salmonella enterica subsp. enterica CCM 3807. The analyzed species of plant with high value of biological activity can be used more in the future, not only in food, but also in cosmetics and pharmaceutical industries.

  12. Infrared spectroscopy of fullerene C60/anthracene adducts

    CERN Document Server

    Garcia-Hernandez, D A; Manchado, A

    2013-01-01

    Recent Spitzer Space Telescope observations of several astrophysical environments such as Planetary Nebulae, Reflection Nebulae, and R Coronae Borealis stars show the simultaneous presence of mid-infrared features attributed to neutral fullerene molecules (i.e., C60) and polycyclic aromatic hydrocarbons (PAHs). If C60 fullerenes and PAHs coexist in fullerene-rich space environments, then C60 may easily form adducts with a number of different PAH molecules; at least with catacondensed PAHs. Here we present the laboratory infrared spectra (~2-25 um) of C60 fullerene and anthracene Dies-Alder mono- and bis-adducts as produced by sonochemical synthesis. We find that C60/anthracene Diels-Alder adducts display spectral features strikingly similar to those from C60 (and C70) fullerenes and other unidentified infrared emission features. Thus, fullerene-adducts - if formed under astrophysical conditions and stable/abundant enough - may contribute to the infrared emission features observed in fullerene-containing circu...

  13. Conjugated linoleic acid isomers: differences in metabolism and biological effects.

    Science.gov (United States)

    Churruca, Itziar; Fernández-Quintela, Alfredo; Portillo, Maria Puy

    2009-01-01

    The term conjugated linoleic acid (CLA) refers to a mixture of linoleic acid positional and geometric isomers, characterized by having conjugated double bonds, not separated by a methylene group as in linoleic acid. CLA isomers appear as a minor component of the lipid fraction, found mainly in meat and dairy products from cows and sheep. The most abundant isomer is cis-9,trans-11, which represents up to 80% of total CLA in food. These isomers are metabolized in the body through different metabolic pathways, but important differences, that can have physiological consequences, are observed between the two main isomers. The trans-10,cis-12 isomer is more efficiently oxidized than the cis-9,trans-11 isomer, due to the position of its double bounds. Interest in CLA arose in its anticarcinogenic action but there is an increasing amount of specific scientific literature concerning the biological effects and properties of CLA. Numerous biological effects of CLA are due to the separate action of the most studied isomers, cis-9,trans-11 and trans-10,cis-12. It is also likely that some effects are induced and/or enhanced by these isomers acting synergistically. Although the cis-9,trans-11 isomer is mainly responsible for the anticarcinogenic effect, the trans-10,cis-12 isomer reduces body fat and it is referred as the most effective isomer affecting blood lipids. As far as insulin function is concerned, both isomers seem to be responsible for insulin resistance in humans. Finally, with regard to the immune system it is not clear whether individual isomers of CLA could act similarly or differently.

  14. Effect of double-leg semi-squats with hip adduction on the vastus medialis oblique of patients with patellofemoral pain syndrome%双足半蹲伴髋内收对髌股疼痛综合征股内斜肌的强化作用

    Institute of Scientific and Technical Information of China (English)

    缪萍; 王楚怀; 潘翠环

    2014-01-01

    目的 采用表面肌电图(sEMG)评估髌股疼痛综合征(PFPS)患者的股四头肌失衡程度,观察PFPS患者各种表面肌电的特征及变化规律,并探讨髋内收对股内斜肌的针对性强化作用机制.方法 将PFPS患者60例按随机数字表法分为病例组和对照组,每组患者30例,分别在双足半蹲伴或不伴髋内收动作时检测股外侧肌(VL)及股内斜肌(VMO)表面肌电图,分析股内、外侧肌时域指标,比较其平衡关系.结果 双足半蹲不伴髋内收动作时,病例组VL的均方根振幅(RMS)和积分肌电值(IEMG)分别为(103.31±44.54) μV和(8.02±3.45) μVs,分别与组内VMO RMS的(85.02 ±41.19) μV和IEMG的(6.72±3.20) μVs比较,差异均有统计学意义(P<0.05).病例组不伴髋内收时VMO的RMS、IEMG与组内伴髋内收时VMO的RMS、IEMG比较,差异均有统计学意义(P<0.05).结论 双足半蹲伴髋内收的动作可以优先强化VMO,使VL与VMO之间达到更好的平衡状态.%Objective To investigate the possible effect of performing double-leg semi-squats with hip adduction on the imbalance between vastus lateralis (VL) and vastus medialis oblique (VMO) muscles of patients with patellofemoral pain syndrome (PFPS).Methods Thirty patients with PFPS were selected to be in the study group,matched with 30 healthy subjects who were enrolled as the control group.Electromyography was used to record VL and VMO activities while the subjects performed double-leg semi-squats (DSs) and double-leg semi-squats with hip adduction (DSs-HA).Results In the study group,when performing DSs,the average RMS was (103.31 ± 44.54) μV and the IEMG was (8.02 ±3.45) μVs for VL.For VMO the RMS was (85.02 ±41.19) μV and the IEMG was (6.72 ±3.20) μVs.The differences in the time domain indexes (RMS,IEMG) between VL and VMO were both significant during DSs (P < 0.05).There was no significant differences during DSs-HA (P > 0.05).The time domain indexes (RMS,IEMG) of VMO were significantly

  15. Bulky DNA Adducts in Cord Blood, Maternal Fruit-and-Vegetable Consumption, and Birth Weight in a European Mother–Child Study (NewGeneris)

    OpenAIRE

    Pedersen, Marie; Schoket, Bernadette; Godschalk, Roger W.; Wright, John; von Stedingk, Hans; Törnqvist, Margareta; Sunyer, Jordi; Nielsen, Jeanette K.; Merlo, Domenico Franco; Mendez, Michelle A.; Meltzer, Helle Margrete; Lukacs, Viktoria; Landström, Anette; Kyrtopoulos, Soterios A; Kovacs, Katalin

    2013-01-01

    Background: Tobacco-smoke, airborne, and dietary exposures to polycyclic aromatic hydrocarbons (PAHs) have been associated with reduced prenatal growth. Evidence from biomarker-based studies of low-exposed populations is limited. Bulky DNA adducts in cord blood reflect the prenatal effective dose to several genotoxic agents including PAHs. Objectives: We estimated the association between bulky DNA adduct levels and birth weight in a multicenter study and examined modification of this associat...

  16. Efficient CO2 capture by tertiary amine-functionalized ionic liquids through Li(+)-stabilized zwitterionic adduct formation.

    Science.gov (United States)

    Yang, Zhen-Zhen; He, Liang-Nian

    2014-01-01

    Highly efficient CO2 absorption was realized through formation of zwitterionic adducts, combining synthetic strategies to ionic liquids (ILs) and coordination. The essence of our strategy is to make use of multidentate cation coordination between Li(+) and an organic base. Also PEG-functionalized organic bases were employed to enhance the CO2-philicity. The ILs were reacted with CO2 to form the zwitterionic adduct. Coordination effects between various lithium salts and neutral ligands, as well as the CO2 capacity of the chelated ILs obtained were investigated. For example, the CO2 capacity of PEG150MeBu2N increased steadily from 0.10 to 0.66 (mol CO2 absorbed per mol of base) through the formation of zwitterionic adducts being stabilized by Li(+).

  17. Arsenic in the aquatic environment - speciation and biological effects

    Energy Technology Data Exchange (ETDEWEB)

    Landner, L. [Swedish Environmental Research Group (MFG)

    1998-03-01

    The present report is a contribution to EC Commission`s undertaking to review existing EC provisions on the substances for which Sweden has been granted transitional provisions. The provisions imply that Sweden may maintain more stringent regulations on four substances until the end of 1998. The present report deals with speciation and biological effects of arsenic in three types of aquatic environments - marine water, estuarine or brackish water and freshwater. The similarity between arsenate and phosphate and the interference in phosphorylation reactions is discussed. It is clear that in Scandinavian inland waters the concentration of phosphorous is on average lower than in most inland waters in continental Europe. However, in most inland waters phosphorus is the limiting factor for phytoplankton development and eutrophication, which means that there is a clear risk for detrimental effects in the great majority of inland waters, also eutrophic waters 167 refs, 27 figs, 12 tabs. Exemption Substances Project (Directive 89/677/EEC)

  18. Modeling of biological doses and mechanical effects on bone transduction

    CERN Document Server

    Rieger, Romain; Jennane, Rachid; 10.1016/j.jtbi.2011.01.003

    2012-01-01

    Shear stress, hormones like parathyroid and mineral elements like calcium mediate the amplitude of stimulus signal which affects the rate of bone remodeling. The current study investigates the theoretical effects of different metabolic doses in stimulus signal level on bone. The model was built considering the osteocyte as the sensing center mediated by coupled mechanical shear stress and some biological factors. The proposed enhanced model was developed based on previously published works dealing with different aspects of bone transduction. It describes the effects of physiological doses variations of Calcium, Parathyroid Hormone, Nitric Oxide and Prostaglandin E2 on the stimulus level sensed by osteocytes in response to applied shear stress generated by interstitial fluid flow. We retained the metabolic factors (Parathyroid Hormone, Nitric Oxide, and Prostaglandin E2) as parameters of bone cell mechanosensitivity because stimulation/inhibition of induced pathways stimulates osteogenic response in vivo. We t...

  19. Detection of adriamycin-DNA adducts by accelerator mass spectrometry.

    Science.gov (United States)

    Coldwell, Kate; Cutts, Suzanne M; Ognibene, Ted J; Henderson, Paul T; Phillips, Don R

    2010-01-01

    There have been many attempts in the past to determine whether significant levels of Adriamycin-DNA adducts form in cells and contribute to the anticancer activity of this agent. Supraclincal drug levels have been required to study drug-DNA adducts because of the lack of sensitivity associated with many of the techniques employed, including liquid scintillation counting of radiolabeled drug. The use of accelerator mass spectrometry (AMS) has provided the first direct evidence of Adriamycin-DNA adduct formation in cells at clinically relevant Adriamycin concentrations. The exceedingly sensitive nature of AMS has enabled over three orders of magnitude increased sensitivity of Adriamycin-DNA adduct detection (compared to liquid scintillation counting) and has revealed adduct formation within an hour of drug treatment. The rigorous protocol required for this approach, together with many notes on the precautions and procedures required in order to ensure that absolute levels of Adriamycin-DNA adducts can be determined with good reproducibility, is outlined in this chapter.

  20. Late biological effects from internal and external exposure

    Energy Technology Data Exchange (ETDEWEB)

    Adams, W.H.

    1985-01-01

    Information on late biological effects of radiation was obtained from the long-term medical followup of a small population of Marshallese accidentally exposed to radioactive fallout from a thermonuclear test in 1954. Endocrine data are compatible with a sequence of nonstochastic radiation effects. The ingestion of radioisotopes of iodine produced clinical thyroid hypofunction in children, biochemical evidence of thyroid dysfunction in some adults, thyroid adenomatous module formation, and, as a possible indirect effect of thyroid damage, at least two cases of pituitary adenoma. In contrast, the only evidence of a stochastic effect has been a real increase in thyroid cancers among the more highly exposed people of Rongelap, none of whom have evidence of residual disease. While three nonthyroidal cancers which are known to be inducible in humans by external irradiation have been documented in the exposed population, three similar cancers have occurred in an unexposed comparison population of Marshallese. Nonstochastic effects of radiation exposure may be common but subtle. In the Marshallese experience the morbidity of delayed nonstochastic effects far exceeds that of the stochastic. 20 refs., 5 figs., 1 tab.

  1. Effect of Organic Loading on Rotating Biological Contactor Efficiency

    Directory of Open Access Journals (Sweden)

    Kossay K. Al-Ahmady

    2005-12-01

    Full Text Available Organic loading (weight per unit time per volume is useful for the design of rotating biological contactors (RBC and for comparison with the other processes such as activated sludge or oxidation ponds. The present study puts emphasis on the significance of this control or design parameter because it allows direct comparison of the RBC system's performance when operated under various circumstances and with different kinds of wastewater. The results of the paper proved that, the COD removal in rotating biological contactor systems is a function of the organic loading rate. However, each of the wastewater concentration and flow rate are also influence on the system efficiency but theirs impact can be combined by the effect of organic loading. The majority of COD removal (40-85 % of the total removal depending on the organic loading applied occurs in the first stages of the system. There is a strong correlation between the organic loading and the concentration of the suspended solids in the rotating biological contactor basin. At higher loadings higher concentrations noted. At a loading of about, (24 g/m2.d suspended solids were 225, 125, 35, and 25 mg/L in the first, second, third and, the fourth stage respectively. To achieve an effluent quality of (BOD < 25 mg/L, COD < 60 mg/L, the system must be operated on organic loadings of about (22 gBOD/m2.d and 65 gCOD/m2.d respectively. For nitrification process, the system must be designed to operate at organic loading of about (10 g/m2.d or less and, the reactor or basin volume should be designed to achieve a hydraulic loading of about (40 L/m2.d or less.

  2. Biological effects due to weak magnetic field on plants

    Science.gov (United States)

    Belyavskaya, N. A.

    2004-01-01

    magnetic field may cause different biological effects at the cellular, tissue and organ levels. They may be functionally related to systems that regulate plant metabolism including the intracellular Ca 2+ homeostasis. However, our understanding of very complex fundamental mechanisms and sites of interactions between weak magnetic fields and biological systems is still incomplete and still deserve strong research efforts.

  3. [DIRECTIONALITY OF THE BIOLOGICAL EFFECT OF DRINKING WATER].

    Science.gov (United States)

    Gibert, K K; Karasev, A K; Marasanov, A V; Stekhin, A A; Iakovleva, G V

    2015-01-01

    There have been performed the studies of the dimensional parameters of peroxide associates in drinking water, per- forming regulatory functions in cellular metabolism, that determine the character of the biological response of the human body to drinking water The direction of action of peroxide associates type Σ [(HO2-(*) ... OH-(*) (H2O) tp)]q, (where (H2O) tp is an associate with the tetragonal structure (Walrafen pentamer Is ice VI), q is the degree of association p--parameter of ion coordination) on the cellular structures of the organism is associated with their quantum properties, determining the macroscopic parameters of the electron wave packets. Research has confirmed the addressness of the nonlocal entering electron to certain cellular structures of the body, which is determined by the structural similarity of centers of condensation of electrons in the cells of systems and organs of the body with the parameters of the electron wave packets in the associates. Methodology for the estimation of the orientation of biological effect of the drinking water to the systems of the body on the base of the analysis of variations in heart rhythm under non-contact influence of water on the human body and its relationship with the dimensional parameters and peroxide activity of associates in drinking water can be suggested for the implementation of screening tests for drinking water quality, taking into account both the individualfeatures of responses of body systems to drinking water and its group action.

  4. Biological vs. physical mixing effects on benthic food web dynamics.

    Directory of Open Access Journals (Sweden)

    Ulrike Braeckman

    Full Text Available Biological particle mixing (bioturbation and solute transfer (bio-irrigation contribute extensively to ecosystem functioning in sediments where physical mixing is low. Macrobenthos transports oxygen and organic matter deeper into the sediment, thereby likely providing favourable niches to lower trophic levels (i.e., smaller benthic animals such as meiofauna and bacteria and thus stimulating mineralisation. Whether this biological transport facilitates fresh organic matter assimilation by the metazoan lower part of the food web through niche establishment (i.e., ecosystem engineering or rather deprives them from food sources, is so far unclear. We investigated the effects of the ecosystem engineers Lanice conchilega (bio-irrigator and Abra alba (bioturbator compared to abiotic physical mixing events on survival and food uptake of nematodes after a simulated phytoplankton bloom. The (13C labelled diatom Skeletonema costatum was added to 4 treatments: (1 microcosms containing the bioturbator, (2 microcosms containing the bio-irrigator, (3 control microcosms and (4 microcosms with abiotic manual surface mixing. Nematode survival and subsurface peaks in nematode density profiles were most pronounced in the bio-irrigator treatment. However, nematode specific uptake (Δδ(13C of the added diatoms was highest in the physical mixing treatment, where macrobenthos was absent and the diatom (13C was homogenised. Overall, nematodes fed preferentially on bulk sedimentary organic material rather than the added diatoms. The total C budget (µg C m(-2, which included TO(13C remaining in the sediment, respiration, nematode and macrobenthic uptake, highlighted the limited assimilation by the metazoan benthos and the major role of bacterial respiration. In summary, bioturbation and especially bio-irrigation facilitated the lower trophic levels mainly over the long-term through niche establishment. Since the freshly added diatoms represented only a limited food

  5. Maternal diet and dioxin-like activity, bulky DNA adducts and micronuclei in mother newborns

    DEFF Research Database (Denmark)

    Pedersen, Marie; Halldorsson, Thorhallur I; Autrup, Herman

    2012-01-01

    was estimated on the basis of maternal food frequency questionnaire (FFQ) completed by the end of pregnancy. Biomarkers were detected in paired blood samples through the dioxin-responsive chemical-activated luciferase expression (CALUX)(®) bioassay, (32)P-postlabelling technique and cytokinesis-block MN assay......Maternal diet can contribute to carcinogenic exposures and also modify effects of environmental exposures on maternal and fetal genetic stability. In this study, associations between maternal diet and the levels of dioxin-like plasma activity, bulky DNA adducts in white blood cells and micronuclei...... dietary variables and the biomarkers measured in maternal and fetal samples were identified. The present study suggests that maternal intake of meats with dark surface contributes to the bulky DNA adduct levels in maternal and umbilical cord blood. Relationship between food preparation and bulky DNA...

  6. A mitomycin-N6-deoxyadenosine adduct isolated from DNA.

    Science.gov (United States)

    Palom, Y; Lipman, R; Musser, S M; Tomasz, M

    1998-03-01

    A minor N6-deoxyadenosine adduct of mitomycin C (MC) was isolated from synthetic oligonucleotides and calf thymus DNA, representing the first adduct of MC and a DNA base other than guanine. The structure of the adduct (8) was elucidated using submilligram quantities of total available material. UV difference spectroscopy, circular dichroism, and electrospray mass spectroscopy as well as chemical transformations were utilized in deriving the structure of 8. A series of synthetic oligonucleotides was designed to probe the specificities of the alkylation of adenine by MC. The nature and frequency of the oligonucleotide-MC adducts formed under conditions of reductive activation of MC were determined by their enzymatic digestion to the nucleoside level followed by quantitative analysis of the products by HPLC. The analyses indicated the following: (i) (A)n sequence is favored over (AT)n for adduct formation; (ii) the alkylation favors the duplex structure; (iii) at adenine sites only monofunctional alkylation occurs; (iv) the adenine-to-alkylation frequency in the model oligonucleotides was 0.3-0.6 relative to guanine alkylation at the 5'-ApG sequence but only 0.02-0.1 relative to guanine alkylation at 5'-CpG. The 5'-phosphodiester linkage of the MC-adenine adduct is resistant to snake venom diesterase. The overall ratio of adenine to guanine alkylation in calf thymus DNA was 0.03, indicating that 8 is a minor MC-DNA adduct relative to MC-DNA adducts at guanine residues in the present experimental residues in the present experimental system. However, the HPLC elution time of 8 coincides with that of a major, unknown MC adduct detected previously in mouse mammary tumor cells treated with radiolabeled MC [Bizanek, R., Chowdary, D., Arai, H., Kasai, M., Hughes, C. S., Sartorelli, A. C., Rockwell, S., and Tomasz, M. (1993) Cancer Res. 53, 5127-5134]. Thus, 8 may be identical or closely related to this major adduct formed in vivo. This possibility can now be tested by

  7. DNA Polymerases η and ζ Combine to Bypass O(2)-[4-(3-Pyridyl)-4-oxobutyl]thymine, a DNA Adduct Formed from Tobacco Carcinogens.

    Science.gov (United States)

    Gowda, A S Prakasha; Spratt, Thomas E

    2016-03-21

    4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) are important human carcinogens in tobacco products. They are metabolized to produce a variety 4-(3-pyridyl)-4-oxobutyl (POB) DNA adducts including O(2)-[4-(3-pyridyl)-4-oxobut-1-yl]thymidine (O(2)-POB-dT), the most abundant POB adduct in NNK- and NNN-treated rodents. To evaluate the mutagenic properties of O(2)-POB-dT, we measured the rate of insertion of dNTPs opposite and extension past O(2)-POB-dT and O(2)-Me-dT by purified human DNA polymerases η, κ, ι, and yeast polymerase ζ in vitro. Under conditions of polymerase in excess, polymerase η was most effective at the insertion of dNTPs opposite O(2)-alkyl-dTs. The time courses were biphasic suggesting the formation of inactive DNA-polymerase complexes. The kpol parameter was reduced approximately 100-fold in the presence of the adduct for pol η, κ, and ι. Pol η was the most reactive polymerase for the adducts due to a higher burst amplitude. For all three polymerases, the nucleotide preference was dATP > dTTP ≫ dGTP and dCTP. Yeast pol ζ was most effective in bypassing the adducts; the kcat/Km values were reduced only 3-fold in the presence of the adducts. The identity of the nucleotide opposite the O(2)-alkyl-dT did not significantly affect the ability of pol ζ to bypass the adducts. The data support a model in which pol η inserts ATP or dTTP opposite O(2)-POB-dT, and then, pol ζ extends past the adduct.

  8. Simultaneous Screening of Glutathione and Cyanide Adducts Using Precursor Ion and Neutral Loss Scans-Dependent Product Ion Spectral Acquisition and Data Mining Tools

    Science.gov (United States)

    Jian, Wenying; Liu, Hua-Fen; Zhao, Weiping; Jones, Elliott; Zhu, Mingshe

    2012-05-01

    Drugs can be metabolically activated to soft and hard electrophiles, which are readily trapped by glutathione (GSH) and cyanide (CN), respectively. These adducts are often detected and structurally characterized using separate tandem mass spectrometry methods. We describe a new method for simultaneous screening of GSH and CN adducts using precursor ion (PI) and neutral loss (NL) scans-dependent product ion spectral acquisition and data mining tools on an triple quadrupole linear ion trap mass spectrometry. GSH, potassium cyanide, and their stable isotope labeled analogues were incubated with liver microsomes and a test compound. Negative PI scan of m/z 272 for detection of GSH adducts and positive NL scans of 27 and 29 Da for detection of CN adducts were conducted as survey scans to trigger acquisition of enhanced resolution (ER) spectrum and subsequent enhanced product ion (EPI) spectrum. Post-acquisition data mining of EPI data set using NL filters of 129 and 27 Da was then performed to reveal the GSH adducts and CN adducts, respectively. Isotope patterns and EPI spectra of the detected adducts were utilized for identification of their molecular weights and structures. The effectiveness of this method was evaluated by analyzing reactive metabolites of nefazodone formed from rat liver microsomes. In addition to known GSH- and CN-trapped reactive metabolites, several new CN adducts of nefazodone were identified. The results suggested that current approach is highly effective in the analysis of both soft and hard reactive metabolites and can be used as a high-throughput method in drug discovery.

  9. 21 CFR 601.26 - Reclassification procedures to determine that licensed biological products are safe, effective...

    Science.gov (United States)

    2010-04-01

    ... licensed biological products are safe, effective, and not misbranded under prescribed, recommended, or... Reclassification procedures to determine that licensed biological products are safe, effective, and not misbranded... for the reclassification of all biological products that have been classified into Category IIIA....

  10. Using cyclodextrins to encapsulate oxygen-centered and carbon-centered radical adducts: the case of DMPO, PBN, and MNP spin traps.

    Science.gov (United States)

    Spulber, Mariana; Schlick, Shulamith

    2010-06-03

    We present electron spin resonance (ESR) experiments that describe the interaction of beta-cyclodextrin (beta-CD) with spin adducts of three spin traps: 5,5-dimethyl-1-pyrroline N-oxide (DMPO), N-tert-butyl-alpha-phenylnitrone (PBN), and 2-methyl-2-nitrosopropane (MNP). The focus was on spin adducts of oxygen-centered radicals trapped by DMPO and PBN and on carbon-centered radical adducts trapped by MNP. The radicals were generated by reaction with hydroxyl radicals and the spin adducts studied were DMPO/OH and PBN/OH, MNP/CH(2)COOH generated in CH(3)COOH, and MNP/CF(2)COOH in CF(2)HCOOH. Di-tert-butyl nitroxide ((CH(3))(3)C)(2)NO (DTBN) was also detected in experiments with MNP as the spin trap. A range of interactions of the spin adducts and DTBN with beta-CD was identified. The presence of beta-CD led to significant stabilization of DMPO/OH and PBN/OH but to a negligible effect on the (14)N hyperfine splitting of the adducts, a(N), indicating that the N-O group is outside the beta-CD cavity. An increase of a(N) was detected for DTBN and MNP/CH(2)COOH in CH(3)COOH in the presence of beta-CD, a result we assigned to bonding at the rim of the host. Experiments with methylated beta-CD (Me beta-CD) provided support for this conclusion. A different type of complexation was detected for DTBN and MNP/CF(2)COOH in CF(2)HCOOH: for specific host concentrations both "in" and "out" species were detected. We suggest that the hydrophobicity of the fluorinated adduct leads to insertion of the adduct inside the host cavity. Calculation of the association constant K(a) indicated the competition between DTBN and the adduct for inclusion in the host. For MNP as spin trap, the two nitroxide radicals (adduct and DTBN) have the same type of interaction with the host: at the rim in acetic acid, and inside the host cavity in CF(2)HCOOH. Experiments with DTBN in the absence of the spin trap and of adducts illuminated the effect of the local polarity and of the pH on the hyperfine

  11. 石蜡疗法配合作业疗法对痉挛型脑瘫患儿拇指内收的效果观察%Effects of Combination of Wax Therapy and Occupational Therapy on Spastic Cerebral Palsy with Thumb Adduction

    Institute of Scientific and Technical Information of China (English)

    邓庆先; 李晓捷; 李晓红; 汤敬华; 张士岭

    2011-01-01

    Objective To observe effects of combination of wax therapy and occupational therapy on spastic cerebral palsy with thumb adduction. Methods 100 cases of children with spastic cerebral palsy were randomly divided into observation group(n= 50) and control group(n= 50). The observation group received occupational therapy and wax therapy, while the control group received only occupational therapy. The effect was compared between the two groups 3 months after treatment. Results The two groups improved significantly 3 months after treatment, while the observation group was better than the control group(P<0. 001). Conclusion Wax therapy combined with occupational therapy have better effects on thumb adduction in spastic cerebral palsy than simple occupational therapy.%目的观察石蜡疗法配合作业疗法治疗痉挛型脑瘫患儿拇指内收的效果.方法 100例痉挛型脑瘫患儿随机分为观察组(n=50)和对照组(n=50),观察组采用作业疗法及石蜡疗法;对照组仅接受作业疗法.治疗3个月后比较两组的疗效.结果治疗后两组患儿均有改善,但观察组显著优于对照组(P<0.001).结论石蜡疗法配合作业疗法可促进痉挛型脑瘫患儿拇指功能的恢复,效果优于单纯作业疗法.

  12. Effect of choline carboxylate ionic liquids on biological membranes.

    Science.gov (United States)

    Rengstl, Doris; Kraus, Birgit; Van Vorst, Matthew; Elliott, Gloria D; Kunz, Werner

    2014-11-01

    Choline carboxylates, ChCm, with m=2-10 and choline oleate are known as biocompatible substances, yet their influence on biological membranes is not well-known, and the effect on human skin has not previously been investigated. The short chain choline carboxylates ChCm with m=2, 4, 6 act as hydrotropes, solubilizing hydrophobic compounds in aqueous solution, while the longer chain choline carboxylates ChCm with m=8, 10 and oleate are able to form micelles. In the present study, the cytotoxicity of choline carboxylates was tested using HeLa and SK-MEL-28 cells. The influence of these substances on liposomes prepared from dipalmitoylphosphatidylcholine (DPPC) was also evaluated to provide insights on membrane interactions. It was observed that the choline carboxylates with a chain length of m>8 distinctly influence the bilayer, while the shorter ones had minimal interaction with the liposomes.

  13. Behavioural biology: an effective and relevant conservation tool.

    Science.gov (United States)

    Buchholz, Richard

    2007-08-01

    'Conservation behaviour' is a young discipline that investigates how proximate and ultimate aspects of the behaviour of an animal can be of value in preventing the loss of biodiversity. Rumours of its demise are unfounded. Conservation behaviour is quickly building a capacity to positively influence environmental decision making. The theoretical framework used by animal behaviourists is uniquely valuable to elucidating integrative solutions to human-wildlife conflicts, efforts to reintroduce endangered species and reducing the deleterious effects of ecotourism. Conservation behaviourists must join with other scientists under the multidisciplinary umbrella of conservation biology without giving up on their focus: the mechanisms, development, function and evolutionary history of individual differences in behaviour. Conservation behaviour is an increasingly relevant tool in the preservation of nature.

  14. Biological effects and equivalent doses in radiotherapy: a software solution

    CERN Document Server

    Voyant, Cyril; Roustit, Rudy; Biffi, Katia; Marcovici, Celine Lantieri

    2013-01-01

    The limits of TDF (time, dose, and fractionation) and linear quadratic models have been known for a long time. Medical physicists and physicians are required to provide fast and reliable interpretations regarding the delivered doses or any future prescriptions relating to treatment changes. We therefore propose a calculation interface under the GNU license to be used for equivalent doses, biological doses, and normal tumor complication probability (Lyman model). The methodology used draws from several sources: the linear-quadratic-linear model of Astrahan, the repopulation effects of Dale, and the prediction of multi-fractionated treatments of Thames. The results are obtained from an algorithm that minimizes an ad-hoc cost function, and then compared to the equivalent dose computed using standard calculators in seven French radiotherapy centers.

  15. Biological Effects on Fruit Fly by N+ ion Beam Implantation

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Mutation induced by low energy ion beam implantation has beenapplied widely both in plants and microbes. However, due to the vacuum limitation, such ion implantation into animals was never studied except for silkworm. In this study, Pupae of fruit fly were irradiated with different dosage N+ ions at energy 20 KeV to study the biological effect of ion beam on animal. The results showed a saddle-like curve exists between incubate rate and dosage. Damage of pupae by ion beam implantation was observed using scanning electron microscope. Some individuals with incomplete wing were obtained after implantation but no similar character was observed in their offspring. Furthermore, about 5.47% mutants with wide variation appeared in M1 generation. Therefore, ion beam implantation could be widely used for mutation breeding.

  16. Hydrodynamic collective effects of active proteins in biological membranes

    Science.gov (United States)

    Koyano, Yuki; Kitahata, Hiroyuki; Mikhailov, Alexander S.

    2016-08-01

    Lipid bilayers forming biological membranes are known to behave as viscous two-dimensional fluids on submicrometer scales; usually they contain a large number of active protein inclusions. Recently, it was shown [A. S. Mikhailov and R. Kapral, Proc. Natl. Acad. Sci. USA 112, E3639 (2015), 10.1073/pnas.1506825112] that such active proteins should induce nonthermal fluctuating lipid flows leading to diffusion enhancement and chemotaxislike drift for passive inclusions in biomembranes. Here, a detailed analytical and numerical investigation of such effects is performed. The attention is focused on the situations when proteins are concentrated within lipid rafts. We demonstrate that passive particles tend to become attracted by active rafts and are accumulated inside them.

  17. Interaction mechanisms and biological effects of static magnetic fields

    Energy Technology Data Exchange (ETDEWEB)

    Tenforde, T.S.

    1994-06-01

    Mechanisms through which static magnetic fields interact with living systems are described and illustrated by selected experimental observations. These mechanisms include electrodynamic interactions with moving, ionic charges (blood flow and nerve impulse conduction), magnetomechanical interactions (orientation and translation of molecules structures and magnetic particles), and interactions with electronic spin states in charge transfer reactions (photo-induced electron transfer in photosynthesis). A general summary is also presented of the biological effects of static magnetic fields. There is convincing experimental evidence for magnetoreception mechanisms in several classes of lower organisms, including bacteria and marine organisms. However, in more highly evolved species of animals, there is no evidence that the interactions of static magnetic fields with flux densities up to 2 Tesla (1 Tesla [T] = 10{sup 4} Gauss) produce either behavioral or physiolocical alterations. These results, based on controlled studies with laboratory animals, are consistent with the outcome of recent epidemiological surveys on human populations exposed occupationally to static magnetic fields.

  18. Effect of Antimicrobial Peptide-Amide: Indolicidin on Biological Membranes

    Directory of Open Access Journals (Sweden)

    Attila Gergely Végh

    2011-01-01

    Full Text Available Indolicidin, a cationic antimicrobial tridecapeptide amide, is rich in proline and tryptophan residues. Its biological activity is intensively studied, but the details how indolicidin interacts with membranes are not fully understood yet. We report here an in situ atomic force microscopic study describing the effect of indolicidin on an artificial supported planar bilayer membrane of dipalmitoyl phosphatidylcholine (DPPC and on purple membrane of Halobacterium salinarum. Concentration dependent interaction of the peptide and membranes was found in case of DPPC resulting the destruction of the membrane. Purple membrane was much more resistant against indolicidin, probably due to its high protein content. Indolicidin preferred the border of membrane disks, where the lipids are more accessible. These data suggest that the atomic force microscope is a powerful tool in the study of indolicidin-membrane interaction.

  19. [The biological effect of fireproof ceramic fibers--literature review].

    Science.gov (United States)

    Krajnow, A

    1996-01-01

    The work presents reports, selected from the world literature, on the studies of biological effect of refractory ceramic fibres, carried out on experimental animals. The discrepancy between the results of studies performed may originate from differences in the distribution of fibre sizes or the durability of fibres in the organism and their surface properties which, in turn, depend on the chemical composition of fibres. In all studies discussed, ceramic fibres generally activated macrophages and they were characterised by a moderate fibrotic activity. A statistically significant increase in the incidence of tumor (mesothelioma) observed in several very important experimental studies may suggest that some types of refractory ceramic fibres show a similar carcinogenic potential to that of natural asbestos: crocidolite or chrysotile.

  20. Investigation on inhibition of biological effects of endothelin

    Institute of Scientific and Technical Information of China (English)

    田青; 赵东; 张继峰; 高连如; 刘胜昔; 杨军; 苏静怡; 张肇康; 汤健; 唐朝枢

    1996-01-01

    The effects of a series of substances on the biological function of endothelin (ET) are reported. The substances used are: synthetic inhibitors of endothelium derived relaxing factors (EDRFs), inhibitor of big-endothelin converting enzyme phosphoramidon, antiserum of endothelin, antagonists of endothelin A receptor BQ123 and JKC301, and two Chinese anti-snake venom herb medicines Lobelia radians Thumb and Taris polyphylla Smith var. chinensis (Franch) Hara. The results showed that inhibiting the production of nitric oxide (NO) could stimulate ET release from vascular endothelium, elevate plasma ET and increase blood pressure. These changes could be reversed by L-arginine (L-Arg), the substrate of nitric oxide synthase (NOS). The amount of ET released by arterial endothelium could be increased or inhibited by inhibiting or stimulating the synthesis of prostacyclin (PGI2). The plasma ET level and blood pressure in both SHR and WKY rats could be decreased by giving phosphoramidon (PhR). The above results i

  1. Effect of Computer Animations Upon Student's Achievement of Biology Education

    Directory of Open Access Journals (Sweden)

    Mehmet YAKIŞAN

    2009-08-01

    Full Text Available The prime purpose of this study is to investigate the effect of computer animation supported biology education upon students’ academic achievement. The study was participated by 97 pre service teachers studying in the first year of university. The data were collected by “Cell Achievement Test” There were control and experimental groups formed and the experimental group was taught with computer animations related with diffusion, osmosis, active transport, protein synthesis, mitosis and meiosis phenomena taking place in cell while the control group was taught with traditional method based on question and answer process. The data obtained were evaluated by t- test and represented by tables and graphs. The results of the study indicated significant differences between the academic achievements of control and experimental groups. The difference is in the favor of the experimental group which revealed the fact the computer animations caused a significant increase in the academic achievements of the students.

  2. Biological Effectiveness and Application of Heavy Ions in Radiation Therapy Described by a Physical and Biological Model

    DEFF Research Database (Denmark)

    Olsen, Kjeld J.; Hansen, Johnny W.

    A description is given of the physical basis for applying track structure theory in the determination of the effectiveness of heavy-ion irradiation of single- and multi-hit target systems. It will be shown that for applying the theory to biological systems the effectiveness of heavy-ion irradiation...... simultaneously in therapy....

  3. Lewis Acid-Base Adduct Approach for High Efficiency Perovskite Solar Cells.

    Science.gov (United States)

    Lee, Jin-Wook; Kim, Hui-Seon; Park, Nam-Gyu

    2016-02-16

    Since the first report on the long-term durable 9.7% solid-state perovskite solar cell employing methylammonium lead iodide (CH3NH3PbI3), mesoporous TiO2, and 2,2',7,7'-tetrakis[N,N-di(4-methoxyphenyl)amino]-9,9'-spirobifluorene (spiro-MeOTAD) in 2012, following the seed technologies on perovskite-sensitized liquid junction solar cells in 2009 and 2011, a surge of interest has been focused on perovskite solar cells due to superb photovoltaic performance and extremely facile fabrication processes. The power conversion efficiency (PCE) of perovskite solar cells reached 21% in a very short period of time. Such an unprecedentedly high photovoltaic performance is due to the intrinsic optoelectronic property of organolead iodide perovskite material. Moreover, a high dielectric constant, sub-millimeter scale carrier diffusion length, an underlying ferroelectric property, and ion migration behavior can make organolead halide perovskites suitable for multifunctionality. Thus, besides solar cell applications, perovskite material has recently been applied to a variety fields of materials science such as photodetectors, light emitting diodes, lasing, X-ray imaging, resistive memory, and water splitting. Regardless of application areas, the growth of a well-defined perovskite layer with high crystallinity is essential for effective utilization of its excellent physicochemical properties. Therefore, an effective methodology for preparation of high quality perovskite layers is required. In this Account, an effective methodology for production of high quality perovskite layers is described, which is the Lewis acid-base adduct approach. In the solution process to form the perovskite layer, the key chemicals of CH3NH3I (or HC(NH2)2I) and PbI2 are used by dissolving them in polar aprotic solvents. Since polar aprotic solvents bear oxygen, sulfur, or nitrogen, they can act as a Lewis base. In addition, the main group compound PbI2 is known to be a Lewis acid. Thus, PbI2 has a chance

  4. Biological effects due to weak magnetic fields on plants

    Science.gov (United States)

    Belyavskaya, N.

    In the evolution process, living organisms have experienced the action of the Earth's magnetic field (MF) that is a natural component of our environment. It is known that a galactic MF induction does not exceed 0.1 nT, since investigations of weak magnetic field (WMF) effects on biological systems have attracted attention of biologists due to planning long-term space flights to other planets where the magnetizing force is near 10-5 Oe. However, the role of WMF and its influence on organisms' functioning are still insufficiently investigated. A large number of experiments with seedlings of different plant species placed in WMF has found that the growth of their primary roots is inhibited during the early terms of germination in comparison with control. The proliferation activity and cell reproduction are reduced in meristem of plant roots under WMF application. The prolongation of total cell reproductive cycle is registered due to the expansion of G phase in1 different plant species as well as of G phase in flax and lentil roots along with2 relative stability of time parameters of other phases of cell cycle. In plant cells exposed to WMF, the decrease in functional activity of genome at early prereplicate period is shown. WMF causes the intensification in the processes of proteins' synthesis and break-up in plant roots. Qualitative and quantitative changes in protein spectrum in growing and differentiated cells of plant roots exposed to WMF are revealed. At ultrastructural level, there are observed such ultrastructural peculiarities as changes in distribution of condensed chromatin and nucleolus compactization in nuclei, noticeable accumulation of lipid bodies, development of a lytic compartment (vacuoles, cytosegresomes and paramural bodies), and reduction of phytoferritin in plastids in meristem cells of pea roots exposed to WMF. Mitochondria are the most sensitive organelle to WMF application: their size and relative volume in cells increase, matrix is electron

  5. Effect of a biological activated carbon filter on particle counts

    Institute of Scientific and Technical Information of China (English)

    Su-hua WU; Bing-zhi DONG; Tie-jun QIAO; Jin-song ZHANG

    2008-01-01

    Due to the importance of biological safety in drinking water quality and the disadvantages which exist in traditional methods of detecting typical microorganisms such as Cryptosporidium and Giardia,it is necessary to develop an alternative.Particle counts is a qualitative measurement of the amount of dissolved solids in water.The removal rate of particle counts was previously used as an indicator of the effectiveness of a biological activated carbon(BAC)filter in removing Cryptosporidium and Giardia.The particle counts in a BAC filter effluent over one operational period and the effects of BAC filter construction and operational parameters were investigated with a 10 m3/h pilot plant.The results indicated that the maximum particle count in backwash remnant water was as high as 1296 count/ml and it needed about 1.5 h to reduce from the maximum to less than 50 count/ml.During the standard filtration period,particle counts stay constant at less than 50 count/ml for 5 d except when influ-enced by sand filter backwash remnant water.The removal rates of particle counts in the BAC filter are related to characteristics of the carbon.For example,a columned carbon and a sand bed removed 33.3% and 8.5% of particles,respectively,while the particle counts in effluent from a cracked BAC filter was higher than that of the influent.There is no significant difference among particle removal rates with different filtration rates.High post-ozone dosage(>2 mg/L)plays an important role in particle count removal;when the dosage was 3 mg/L,the removal rates by carbon layers and sand beds decreased by 17.5% and increased by 9.5%,respectively,compared with a 2 mg/L dosage.

  6. Benzene-derived N2-(4-hydroxyphenyl)-deoxyguanosine adduct: UvrABC incision and its conformation in DNA

    Energy Technology Data Exchange (ETDEWEB)

    Hang, Bo; Rodriguez, Ben; Yang, Yanu; Guliaev, Anton B.; Chenna, Ahmed

    2010-06-14

    Benzene, a ubiquitous human carcinogen, forms DNA adducts through its metabolites such as p-benzoquinone (p-BQ) and hydroquinone (HQ). N(2)-(4-Hydroxyphenyl)-2'-deoxyguanosine (N(2)-4-HOPh-dG) is the principal adduct identified in vivo by (32)P-postlabeling in cells or animals treated with p-BQ or HQ. To study its effect on repair specificity and replication fidelity, we recently synthesized defined oligonucleotides containing a site-specific adduct using phosphoramidite chemistry. We here report the repair of this adduct by Escherichia coli UvrABC complex, which performs the initial damage recognition and incision steps in the nucleotide excision repair (NER) pathway. We first showed that the p-BQ-treated plasmid was efficiently cleaved by the complex, indicating the formation of DNA lesions that are substrates for NER. Using a 40-mer substrate, we found that UvrABC incises the DNA strand containing N(2)-4-HOPh-dG in a dose- and time-dependent manner. The specificity of such repair was also compared with that of DNA glycosylases and damage-specific endonucleases of E. coli, both of which were found to have no detectable activity toward N(2)-4-HOPh-dG. To understand why this adduct is specifically recognized and processed by UvrABC, molecular modeling studies were performed. Analysis of molecular dynamics trajectories showed that stable G:C-like hydrogen bonding patterns of all three Watson-Crick hydrogen bonds are present within the N(2)-4-HOPh-G:C base pair, with the hydroxyphenyl ring at an almost planar position. In addition, N(2)-4-HOPh-dG has a tendency to form more stable stacking interactions than a normal G in B-type DNA. These conformational properties may be critical in differential recognition of this adduct by specific repair enzymes.

  7. Genetic polymorphisms in catalase and CYP1B1 determine DNA adduct formation by benzo(a)pyrene ex vivo.

    Science.gov (United States)

    Schults, Marten A; Chiu, Roland K; Nagle, Peter W; Wilms, Lonneke C; Kleinjans, Jos C; van Schooten, Frederik J; Godschalk, Roger W

    2013-03-01

    Genetic polymorphisms can partially explain the large inter-individual variation in DNA adduct levels following exposure to polycyclic aromatic hydrocarbons. Effects of genetic polymorphisms on DNA adduct formation are difficult to assess in human studies because exposure misclassification attenuates underlying relationships. Conversely, ex vivo studies offer the advantage of controlled exposure settings, allowing the possibility to better elucidate genotype-phenotype relationships and gene-gene interactions. Therefore, we exposed lymphocytes of 168 non-smoking volunteers ex vivo to the environmental pollutant benzo(a)pyrene (BaP) and BaP-related DNA adducts were quantified. Thirty-four genetic polymorphisms were assessed in genes involved in carcinogen metabolism, oxidative stress and DNA repair. Polymorphisms in catalase (CAT, rs1001179) and cytochrome P450 1B1 (CYP1B1, rs1800440) were significantly associated with DNA adduct levels, especially when combined. Moreover, reverse transcription-polymerase chain reaction (RT-PCR) analysis in a subset of 30 subjects revealed that expression of catalase correlated strongly with expression of CYP1B1 (R = 0.92, P CYP1B1 and how they simultaneously affect BaP-related DNA adduct levels, catalase expression was transiently knocked down in the human lung epithelial cell line A549. Although catalase knockdown did not immediately change CYP1B1 gene expression, recovery of catalase expression 8 h after the knockdown coincided with a 2.2-fold increased expression of CYP1B1 (P polymorphism in the promoter region of CAT may determine the amount and activity of catalase, which may subsequently regulate the expression of CYP1B1. As a result, both genetic polymorphisms modulate DNA adduct levels in lymphocytes by BaP ex vivo.

  8. Tissue distribution of DNA adducts and their persistence in blood of mice exposed to benzene

    Energy Technology Data Exchange (ETDEWEB)

    Guilan Li; Wang Chunguang; Songnian Yin [Institute of Occupational Medicine Chinese Academy of Preventive Medicine, Beijing (China); Weidong Xin [Medical College of Qingdao, Shandong Province (China)

    1996-12-01

    Chemicals combine with DNA, resulting in DNA damage, which could initiate carcinogenesis. To study whether benzene or benzene metabolites bind to DNA, DNA adducts in various tissues and their persistence in leukocytes were examined using the {sup 32}P-postlabeling assay. LACA mice were dosed in with benzene at 500 mg/kg bw twice daily for 5 days. Two additional spots of DNA adducts are formed in bone marrow cells, liver cells, and peripheral blood compared with control mice. The relative adduct labeling values are 10.39, 11.32, and 13.77 adducts; x 10{sup -8} nucleotides in these tissues, respectively. DNA adducts in blood leukocytes were observed at 1, 4, 7, 14, and 21 days after exposure to benzene, but adduct levels decreased as a function of time. Relative adduct labeling of {open_quotes}adduct B{close_quotes} declined linearly but mildly, while {open_quotes}adduct C{close_quotes} displayed a stepwise decrease. The relative adduct labeling values of both these adducts at day 14 were 50% of those at day 1 after the last treatment. Both adducts were still detectable at day 21 after benzene exposure. These studies demonstrate that benzene could induce DNA adducts; in bone marrow, liver, and white blood cells of mice dosed with benzene and that measurement of adducts in white blood cells may be useful as a biomarker to predict carcinogenic risk of benzene to workers exposed to benzene. 9 refs., 3 figs.

  9. Generation of 5,5-dimethyl-1-pyrroline N-oxide hydroxyl and scavenger radical adducts from copper/H2O2 mixtures: effects of metal ion chelation and the search for high-valent metal-oxygen intermediates.

    Science.gov (United States)

    Burkitt, M J; Tsang, S Y; Tam, S C; Bremner, I

    1995-10-20

    A metal-catalyzed nucleophilic addition mechanism for the formation of radical adducts of the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) has been described recently (K. Makino, T. Hagiwara, A. Hagi, M. Nishi, and A. Murakami, 1990, Biochem. Biophys. Res. Commun. 172, 1073-1080; P. M. Hanna, W. Chamulitrat, and R. P. Mason, 1992, Arch. Biochem. Biophys. 296, 640-644). In the present investigation, we have demonstrated that the recently reported inhibition of copper-dependent hydroxyl radical formation by the complexing agent 1,10-phenanthroline (OP), which appears to contradict the well-known chemical nuclease properties of CuI(OP)2, is an artifact resulting from an inhibition of the nucleophilic addition of water to DMPO by OP (A. C. Mello-Filho and R. Meneghini, 1991, Mutat. Res. 251, 109-113). Copper bound to OP was found to be a good catalyst of hydroxyl radical formation: the CuII(OP)2 complex can be reduced by H2O2 and the CuI(OP)2 generated reacts with the peroxide to form .OH. In contrast, no evidence could be obtained for oxidant formation from the CuII(aq)/H2O2 reaction system, despite the detection of a prominent signal from the DMPO hydroxyl radical adduct (DMPO/.OH) (the formation of which was due solely to the nucleophilic addition of water to DMPO). The failure to generate an oxidant in this reaction mixture was attributed to the failure of hydrogen peroxide to reduce CuII(aq), as hydroxyl radical formation did occur when CuI(aq) was added directly to H2O2. However, in order to account for the high concentration of alpha-hydroxyethanol radicals detected when ethanol was included in the CuI(aq)/H2O2 reaction, the possibility that an oxidant in addition to .OH (e.g., CuO+) is generated is discussed.

  10. Creating context for the use of DNA adduct data in cancer risk assessment: I. Proposed framework for data organization *

    Science.gov (United States)

    The assessment of human cancer risk from chemical exposure requires the integration of diverse types of data. Such data involve effects at the cell and tissue levels. This report focuses on the specific utility of one type of data, namely DNA adducts. Emphasis is placed on the ap...

  11. The effect of green tea on radiation-induced late biological effect in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Ho; Kim, Se Ra; Lee, Hae June; Jo, Sung Kee [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    2004-07-01

    This study was performed to determine the effect of Green tea on the late biological effect of mice irradiated with 3 Gy of gamma-radiation. There were various findings including hematopoietic and lymphoid tumor, lung cancer, ovarian cancer and cancer of other lesions. Further studies are needed to characterize better the protective nature of active compounds.

  12. Complex relationships between occupation, environment, DNA adducts, genetic polymorphisms and bladder cancer in a case-control study using a structural equation modeling.

    Science.gov (United States)

    Porru, Stefano; Pavanello, Sofia; Carta, Angela; Arici, Cecilia; Simeone, Claudio; Izzotti, Alberto; Mastrangelo, Giuseppe

    2014-01-01

    DNA adducts are considered an integrate measure of carcinogen exposure and the initial step of carcinogenesis. Their levels in more accessible peripheral blood lymphocytes (PBLs) mirror that in the bladder tissue. In this study we explore whether the formation of PBL DNA adducts may be associated with bladder cancer (BC) risk, and how this relationship is modulated by genetic polymorphisms, environmental and occupational risk factors for BC. These complex interrelationships, including direct and indirect effects of each variable, were appraised using the structural equation modeling (SEM) analysis. Within the framework of a hospital-based case/control study, study population included 199 BC cases and 213 non-cancer controls, all Caucasian males. Data were collected on lifetime smoking, coffee drinking, dietary habits and lifetime occupation, with particular reference to exposure to aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs). No indirect paths were found, disproving hypothesis on association between PBL DNA adducts and BC risk. DNA adducts were instead positively associated with occupational cumulative exposure to AAs (p = 0.028), whereas XRCC1 Arg 399 (poccupational cumulative exposure to AAs with DNA adducts and BC risk, strengthening the central role of AAs in bladder carcinogenesis. However the lack of an association between PBL DNA adducts and BC risk advises that these snapshot measurements are not representative of relevant exposures. This would envisage new scenarios for biomarker discovery and new challenges such as repeated measurements at different critical life stages.

  13. Mutagenic Effects of Iron Oxide Nanoparticles on Biological Cells.

    Science.gov (United States)

    Dissanayake, Niluka M; Current, Kelley M; Obare, Sherine O

    2015-09-30

    In recent years, there has been an increased interest in the design and use of iron oxide materials with nanoscale dimensions for magnetic, catalytic, biomedical, and electronic applications. The increased manufacture and use of iron oxide nanoparticles (IONPs) in consumer products as well as industrial processes is expected to lead to the unintentional release of IONPs into the environment. The impact of IONPs on the environment and on biological species is not well understood but remains a concern due to the increased chemical reactivity of nanoparticles relative to their bulk counterparts. This review article describes the impact of IONPs on cellular genetic components. The mutagenic impact of IONPs may damage an organism's ability to develop or reproduce. To date, there has been experimental evidence of IONPs having mutagenic interactions on human cell lines including lymphoblastoids, fibroblasts, microvascular endothelial cells, bone marrow cells, lung epithelial cells, alveolar type II like epithelial cells, bronchial fibroblasts, skin epithelial cells, hepatocytes, cerebral endothelial cells, fibrosarcoma cells, breast carcinoma cells, lung carcinoma cells, and cervix carcinoma cells. Other cell lines including the Chinese hamster ovary cells, mouse fibroblast cells, murine fibroblast cells, Mytilus galloprovincialis sperm cells, mice lung cells, murine alveolar macrophages, mice hepatic and renal tissue cells, and vero cells have also shown mutagenic effects upon exposure to IONPs. We further show the influence of IONPs on microorganisms in the presence and absence of dissolved organic carbon. The results shed light on the OPEN ACCESS Int. J. Mol. Sci. 2015, 16 23483 transformations IONPs undergo in the environment and the nature of the potential mutagenic impact on biological cells.

  14. Maternal diet and dioxin-like activity, bulky DNA adducts and micronuclei in mother-newborns.

    Science.gov (United States)

    Pedersen, Marie; Halldorsson, Thorhallur I; Autrup, Herman; Brouwer, Abraham; Besselink, Harrie; Loft, Steffen; Knudsen, Lisbeth E

    2012-06-01

    Maternal diet can contribute to carcinogenic exposures and also modify effects of environmental exposures on maternal and fetal genetic stability. In this study, associations between maternal diet and the levels of dioxin-like plasma activity, bulky DNA adducts in white blood cells and micronuclei (MN) in lymphocytes from mother to newborns were examined. From 98 pregnant women living in the greater area of Copenhagen, Denmark in 2006-2007, maternal peripheral blood and umbilical cord blood were collected, together with information on health, environmental exposure and lifestyle. Maternal diet was estimated on the basis of maternal food frequency questionnaire (FFQ) completed by the end of pregnancy. Biomarkers were detected in paired blood samples through the dioxin-responsive chemical-activated luciferase expression (CALUX)(®) bioassay, (32)P-postlabelling technique and cytokinesis-block MN assay. Maternal preference for meats with dark surface were significantly associated with higher bulky DNA adducts in both maternal (β 95%CI; 0.46 (0.08, 0.84)) and cord blood (β 95%CI; 0.46 (0.05, 0.86)) before and after adjustment for potential confounders. No other significant associations between the 18 dietary variables and the biomarkers measured in maternal and fetal samples were identified. The present study suggests that maternal intake of meats with dark surface contributes to the bulky DNA adduct levels in maternal and umbilical cord blood. Relationship between food preparation and bulky DNA adducts appear to be captured by a FFQ while potential associations for other biomarkers might be more complex or need larger sample size.

  15. Maternal diet and dioxin-like activity, bulky DNA adducts and micronuclei in mother-newborns

    Energy Technology Data Exchange (ETDEWEB)

    Pedersen, Marie, E-mail: mpedersen@creal.cat [Section of Environmental Health, Department of Public Health, University of Copenhagen, CSS, Oester Farimagsgade, Copenhagen K (Denmark); Halldorsson, Thorhallur I., E-mail: lur@ssi.dk [Faculty of Food Science and Nutrition, School of Health Sciences, University of Iceland Reykjavik (Iceland); Center for Fetal Programming, Department of Epidemiology, Statens Serum Institute, Copenhagen (Denmark); Autrup, Herman, E-mail: ha@mil.au.dk [School of Public Health, Department of Environmental and Occupational Medicine, Aarhus University, Aarhus (Denmark); Brouwer, Abraham, E-mail: Bram.Brouwer@bds.nl [BioDetection Systems B.V., Amsterdam (Netherlands); Besselink, Harrie, E-mail: Harrie.Besselink@bds.nl [BioDetection Systems B.V., Amsterdam (Netherlands); Loft, Steffen, E-mail: stl@sund.ku.dk [Section of Environmental Health, Department of Public Health, University of Copenhagen, CSS, Oester Farimagsgade, Copenhagen K (Denmark); Knudsen, Lisbeth E., E-mail: liek@sund.ku.dk [Section of Environmental Health, Department of Public Health, University of Copenhagen, CSS, Oester Farimagsgade, Copenhagen K (Denmark)

    2012-06-01

    Maternal diet can contribute to carcinogenic exposures and also modify effects of environmental exposures on maternal and fetal genetic stability. In this study, associations between maternal diet and the levels of dioxin-like plasma activity, bulky DNA adducts in white blood cells and micronuclei (MN) in lymphocytes from mother to newborns were examined. From 98 pregnant women living in the greater area of Copenhagen, Denmark in 2006-2007, maternal peripheral blood and umbilical cord blood were collected, together with information on health, environmental exposure and lifestyle. Maternal diet was estimated on the basis of maternal food frequency questionnaire (FFQ) completed by the end of pregnancy. Biomarkers were detected in paired blood samples through the dioxin-responsive chemical-activated luciferase expression (CALUX){sup Registered-Sign} bioassay, {sup 32}P-postlabelling technique and cytokinesis-block MN assay. Maternal preference for meats with dark surface were significantly associated with higher bulky DNA adducts in both maternal ({beta} 95%CI; 0.46 (0.08, 0.84)) and cord blood ({beta} 95%CI; 0.46 (0.05, 0.86)) before and after adjustment for potential confounders. No other significant associations between the 18 dietary variables and the biomarkers measured in maternal and fetal samples were identified. The present study suggests that maternal intake of meats with dark surface contributes to the bulky DNA adduct levels in maternal and umbilical cord blood. Relationship between food preparation and bulky DNA adducts appear to be captured by a FFQ while potential associations for other biomarkers might be more complex or need larger sample size.

  16. Signal transduction in light–oxygen–voltage receptors lacking the adduct-forming cysteine residue

    Science.gov (United States)

    Yee, Estella F.; Diensthuber, Ralph P.; Vaidya, Anand T.; Borbat, Peter P.; Engelhard, Christopher; Freed, Jack H.; Bittl, Robert; Möglich, Andreas; Crane, Brian R.

    2015-01-01

    Light–oxygen–voltage (LOV) receptors sense blue light through the photochemical generation of a covalent adduct between a flavin-nucleotide chromophore and a strictly conserved cysteine residue. Here we show that, after cysteine removal, the circadian-clock LOV-protein Vivid still undergoes light-induced dimerization and signalling because of flavin photoreduction to the neutral semiquinone (NSQ). Similarly, photoreduction of the engineered LOV histidine kinase YF1 to the NSQ modulates activity and downstream effects on gene expression. Signal transduction in both proteins hence hinges on flavin protonation, which is common to both the cysteinyl adduct and the NSQ. This general mechanism is also conserved by natural cysteine-less, LOV-like regulators that respond to chemical or photoreduction of their flavin cofactors. As LOV proteins can react to light even when devoid of the adduct-forming cysteine, modern LOV photoreceptors may have arisen from ancestral redox-active flavoproteins. The ability to tune LOV reactivity through photoreduction may have important implications for LOV mechanism and optogenetic applications. PMID:26648256

  17. Molecular structures of five adducts assembled from p-dimethylaminobenzaldehyde and organic acids

    Science.gov (United States)

    Jin, Shouwen; Wang, Lanqing; Liu, Hui; Liu, Li; Zhang, Huan; Wang, Daqi; Li, Minghui; Guo, Jianzhong; Guo, Ming

    2016-07-01

    Five adducts 1-5 derived from p-dimethylaminobenzaldehyde have been prepared and characterized by X-ray diffraction analysis, IR, mp, and elemental analysis. Of the five adducts two are organic salts (1, and 2) and the other three (3-5) are cocrystals. In salts 1, and 2, the L molecules are protonated. The supramolecular architectures of the adducts 1-5 involve extensive intermolecular N-H⋯O, O-H⋯O, O-H⋯S, and C-H⋯O hydrogen bonds as well as other non-covalent interactions. The role of weak and strong non-covalent interactions in the crystal packing is ascertained. The complexes displayed 2D/3D framework structure for the synergistic effect of the various non-covalent interactions. The results presented herein tell that the strength and directionality of the N-H⋯O, O-H⋯O, and O-H⋯S hydrogen bonds between organic acids and p-dimethylaminobenzaldehyde are sufficient to bring about the formation of binary cocrystals or organic salts.

  18. Protein adducts of the prostate carcinogen PhIP in children

    Energy Technology Data Exchange (ETDEWEB)

    Lawrence Livermore National Laboratory

    2004-02-20

    Prostate cancer is the second leading cause of cancer death in men in the United States. few epidemiology studies have indicated that exposure to PhIP, a rodent prostate carcinogen formed in meat during cooking, may be an important risk factor for prostate cancer in humans. Therefore, a highly sensitive biomarker assay is urgently needed to clarify the role of PhIP in prostate cancer. The goal of this project is to develop an assay that can be used to more accurately quantify human exposure to PhIP and potential prostate cancer risk. Our hypothesis is that an Accelerator Mass Spectrometry-based method can be developed to measure protein adducts of PhIP in the blood of humans. This will provide a measure of the internal dose, as well as the capacity for carcinogen bioactivation to a form that can initiate the cancer process. Towards this goal, we have characterized an adduct formed by PhIP in vitro with the amino acid cysteine. This adduct should provide a biomarker of dietary PhIP exposure and potential prostate cancer risk that could be used to identify individuals for prevention and for monitoring the effect chemoprevention strategies.

  19. A three-dimensional model of vocal fold abduction/adduction

    Science.gov (United States)

    Hunter, Eric J.; Titze, Ingo R.; Alipour, Fariborz

    2004-04-01

    A three-dimensional biomechanical model of tissue deformation was developed to simulate dynamic vocal fold abduction and adduction. The model was made of 1721 nearly incompressible finite elements. The cricoarytenoid joint was modeled as a rocking-sliding motion, similar to two concentric cylinders. The vocal ligament and the thyroarytenoid muscle's fiber characteristics were implemented as a fiber-gel composite made of an isotropic ground substance imbedded with fibers. These fibers had contractile and/or passive nonlinear stress-strain characteristics. The verification of the model was made by comparing the range and speed of motion to published vocal fold kinematic data. The model simulated abduction to a maximum glottal angle of about 31°. Using the posterior-cricoarytenoid muscle, the model produced an angular abduction speed of 405° per second. The system mechanics seemed to favor abduction over adduction in both peak speed and response time, even when all intrinsic muscle properties were kept identical. The model also verified the notion that the vocalis and muscularis portions of the thyroarytenoid muscle play significantly different roles in posturing, with the muscularis portion having the larger effect on arytenoid movement. Other insights into the mechanisms of abduction/adduction were given.

  20. Organocatalytic removal of formaldehyde adducts from RNA and DNA bases

    Science.gov (United States)

    Karmakar, Saswata; Harcourt, Emily M.; Hewings, David S.; Lovejoy, Alexander F.; Kurtz, David M.; Ehrenschwender, Thomas; Barandun, Luzi J.; Roost, Caroline; Alizadeh, Ash A.; Kool, Eric T.

    2015-09-01

    Formaldehyde is universally used to fix tissue specimens, where it forms hemiaminal and aminal adducts with biomolecules, hindering the ability to retrieve molecular information. Common methods for removing these adducts involve extended heating, which can cause extensive degradation of nucleic acids, particularly RNA. Here, we show that water-soluble bifunctional catalysts (anthranilates and phosphanilates) speed the reversal of formaldehyde adducts of mononucleotides over standard buffers. Studies with formaldehyde-treated RNA oligonucleotides show that the catalysts enhance adduct removal, restoring unmodified RNA at 37 °C even when extensively modified, while avoiding the high temperatures that promote RNA degradation. Experiments with formalin-fixed, paraffin-embedded cell samples show that the catalysis is compatible with common RNA extraction protocols, with detectable RNA yields increased by 1.5-2.4-fold using a catalyst under optimized conditions and by 7-25-fold compared with a commercial kit. Such catalytic strategies show promise for general use in reversing formaldehyde adducts in clinical specimens.

  1. Glutathione Adduct Patterns of Michael-Acceptor Carbonyls.

    Science.gov (United States)

    Slawik, Christian; Rickmeyer, Christiane; Brehm, Martin; Böhme, Alexander; Schüürmann, Gerrit

    2017-02-22

    Glutathione (GSH) has so far been considered to facilitate detoxification of soft organic electrophiles through covalent binding at its cysteine (Cys) thiol group, followed by stepwise catalyzed degradation and eventual elimination along the mercapturic acid pathway. Here we show that in contrast to expectation from HSAB theory, Michael-acceptor ketones, aldehydes and esters may form also single, double and triple adducts with GSH involving β-carbon attack at the much harder N-terminus of the γ-glutamyl (Glu) unit of GSH. In particular, formation of the GSH-N single adduct contradicts the traditional view that S alkylation always forms the initial reaction of GSH with Michael-acceptor carbonyls. To this end, chemoassay analyses of the adduct formation of GSH with nine α,β-unsaturated carbonyls employing high performance liquid chromatography and tandem mass spectrometry have been performed. Besides enriching the GSH adductome and potential biomarker applications, electrophilic N-terminus functio-nalization is likely to impair GSH homeostasis substantially through blocking the γ-glutamyl transferase catalysis of the first breakdown step of modified GSH, and thus its timely reconstitution. The discussion includes a comparison with cyclic adducts of GSH and furan metabolites as reported in literature, and quantum chemically calculated thermodynamics of hard-hard, hard-soft and soft-soft adducts.

  2. Effect of Sedimentation on Treated Greywater Through Rotating Biological Contactor

    Directory of Open Access Journals (Sweden)

    Ashfaque Ahmed Pathan

    2016-06-01

    Full Text Available The aim of this paper was to study the effect of sedimentation on effluent of a pilot scale Rotating Biological Contactor (RBC. The treated greywater was given three hours sedimentation period and samples were analyzed to observe the effect of sedimentations under variousflow rates. Greywater was separated from the black water and collected in the collection tank and then it was pumped to an overhead tank. This tank supplied a regulated continuous flow of greywater into the RBC chamber at the required flow rate ranging between 0.28 to 1.89 l/min. A pilot scale RBC simulator was developed and placed outside a hall of residence at National Center of Excellence in Analytical Chemistry, Sindh University, Jamshoro. The simulator was operated at the rotational speed of discs of 1.7 rpm. The disks were uneven and textured so as to encourage growth of bacteria on them. These discs were immersed about 40 percent in the greywater.The simulator produced effluent of significant quality and was found efficient in removal of BOD5, COD and TSS as 85%, 68% and 95% respectively.

  3. New Scientific Pearl about Biologic Effect of Ionizing Radiation

    Directory of Open Access Journals (Sweden)

    S. A. Alamdaran

    2008-01-01

    Full Text Available Soon after the discovery of X-ray by Rontgen in 1895, it became evident that radiation can cause some somatic damage to tissues. The hazards of X-ray exposure were clearly known when many large hospitals had radiology departments. The greatest increased in knowledge about X-ray risks had accrued from the dropping of the two atomic bombs in Japan in 1945 and some other atomic accident. For example, among the Japanese bomb survivors from Hiroshima and Nagasaki, there have been about 400 extra cancer deaths. These were the origin of radiology personnel and people fear from radiation exposure and resistant in against simple X-ray exam (radiophobia. However, new scientific data on the effects radiation on survivors, especially about biologic effect of ionizing rays, background radiation exposure, amount of endogenous radiation, hormosis phenomenon and comparison radiation risk with other risk over lifetime are still being continuously revised and risk estimates updated. Fundamentally, this risk is much"nlower than whatever already estimated and it is insignificant in diagnostic domain. Better perception of physician from these instances help to prevent of false radiophobia and to make proper use of diagnostic and therapeutic advantages of ionizing beam.

  4. [Effects of decitabine on biological behavior of U266 cells].

    Science.gov (United States)

    Wang, Mei-Fang; Yang, Lin-Hua; Dong, Chun-Xia; Zhang, Rui-Juan; Zhang, Jian-Hua; Guo, Zhi-Ping; Chen, Jian-Fang; Zhagn, Li; Feng, Da-Wei

    2011-08-01

    This study was aimed to explore the effects of decitabine on the biological behaviour of U266 cells in vitro so as to provide a new thinking and experiment basis, as well as new evidences for the pathogenesis of multiple myeloma. MTT and colony formation assays were used to evaluate the impact of decitabine on the ability of proliferation of U266 cells; flow cytometry was used to analyze the cell distribution in cell cycle; transwell chamber and matrigel assays were used to observe the ability of migration and invasion. The results indicated that decitabine could significantly suppress the proliferation of U266 cells in time-and dose-dependent manners. The flow cytometric analysis demonstrated that the cells in G(0)-G(1) phase significantly increased while the cells in S and G(2)/M phase decreased. The migration and matrigel invading tests showed that the number of cells moving into under chamber of transwell decreased after U266 cells treated with decitabine. It is concluded that decitabine may act as an effective drug for MM by inhibiting the proliferation, migration and invasion ability, and the specific mechanism needs to be deeply explored.

  5. 4-hydroxynonenal protein adducts: Key mediator in Rett syndrome oxinflammation.

    Science.gov (United States)

    Valacchi, Giuseppe; Pecorelli, Alessandra; Cervellati, Carlo; Hayek, Joussef

    2017-01-05

    In the last 15 years a strong correlation between oxidative stress (OxS) and Rett syndrome (RTT), a rare neurodevelopmental disorder known to be caused in 95% of the cases, by a mutation in the methyl-CpG-binding protein 2 (MECP2) gene, has been well documented. Here, we revised, summarized and discussed the current knowledge on the role of lipid peroxidation byproducts, with special emphasis on 4-hydroxynonenal (4HNE), in RTT pathophysiology. The posttranslational modifications of proteins via 4HNE, known as 4HNE protein adducts (4NHE-PAs), causing detrimental effects on protein functions, appear to contribute to the clinical severity of the syndrome, since their levels increase significantly during the subsequent 4 clinical stages, reaching the maximum degree at stage 4, represented by a late motor deterioration. In addition, 4HNE-PA are only partially removed due to the compromised functionality of the proteasome activity, contributing therefore to the cellular damage in RTT. All this will lead to a characteristic subclinical inflammation, defined "OxInflammation", derived by a positive feedback loop between OxS byproducts and inflammatory mediators that in a long run further aggravates the clinical features of RTT patients. Therefore, in a pathology completely orphan of any therapy, aiming 4HNE as a therapeutic target could represent a coadjuvant treatment with some beneficial impact in these patients.‬‬‬.

  6. Cellulose based hybrid hydroxylated adducts for polyurethane foams

    Science.gov (United States)

    De Pisapia, Laura; Verdolotti, Letizia; Di Mauro, Eduardo; Di Maio, Ernesto; Lavorgna, Marino; Iannace, Salvatore

    2012-07-01

    Hybrid flexible polyurethane foams (HPU) were synthesized by using a hybrid hydroxilated adduct (HHA) based on renewable resources. In particular the HHA was obtained by dispersing cellulose wastes in colloidal silica at room temperature, pressure and humidity. The colloidal silica was selected for its ability of modifying the cellulose structure, by inducing a certain "destructurization" of the crystalline phase, in order to allow cellulose to react with di-isocyanate for the final synthesis of the polyurethane foam. In fact, cellulose-polysilicate complexes are engaged in the reaction with the isocyanate groups. This study provides evidence of the effects of the colloidal silica on the cellulose structure, namely, a reduction of the microfiber cellulose diameter and the formation of hydrogen bonds between the polysilicate functional groups and the hydroxyl groups of the cellulose, as assessed by IR spectroscopy and solid state NMR. The HHA was added to a conventional polyol in different percentages (between 5 and 20%) to synthesize HPU in presence of catalysts, silicone surfactant and diphenylmethane diisocyanate (MDI). The mixture was expanded in a mold and cured for two hours at room temperature. Thermal analysis, optical microscopy and mechanical tests were performed on the foams. The results highlighted an improvement of thermal stability and a decrease of the cell size with respect neat polyurethane foam. Mechanical tests showed an improvement of the elastic modulus and of the damping properties with increasing HHA amount.

  7. 21 CFR 601.25 - Review procedures to determine that licensed biological products are safe, effective, and not...

    Science.gov (United States)

    2010-04-01

    ... biological products are safe, effective, and not misbranded under prescribed, recommended, or suggested... determine that licensed biological products are safe, effective, and not misbranded under prescribed, recommended, or suggested conditions of use. For purposes of reviewing biological products that have...

  8. The biological effects of ionising radiation on Crustaceans: A review

    Energy Technology Data Exchange (ETDEWEB)

    Fuller, Neil; Lerebours, Adélaïde [Institute of Marine Sciences, School of Biological Sciences, University of Portsmouth, Ferry Road, Portsmouth, Hampshire PO4 9LY (United Kingdom); Smith, Jim T. [School of Earth & Environmental Sciences, University of Portsmouth, Burnaby Building, Burnaby Road, Portsmouth, Hampshire PO1 3QL (United Kingdom); Ford, Alex T., E-mail: alex.ford@port.ac.uk [Institute of Marine Sciences, School of Biological Sciences, University of Portsmouth, Ferry Road, Portsmouth, Hampshire PO4 9LY (United Kingdom)

    2015-10-15

    Highlights: • We comprehensively review the effects of ionising radiation in crustaceans. • Current environmental radioprotection levels found to be inadequate in some cases. • Mutation is shown to be a sensitive endpoint of radiation exposure. • Lowest observed effect dose rate varies by orders of magnitude. - Abstract: Historic approaches to radiation protection are founded on the conjecture that measures to safeguard humans are adequate to protect non-human organisms. This view is disparate with other toxicants wherein well-developed frameworks exist to minimise exposure of biota. Significant data gaps for many organisms, coupled with high profile nuclear incidents such as Chernobyl and Fukushima, have prompted the re-evaluation of our approach toward environmental radioprotection. Elucidating the impacts of radiation on biota has been identified as priority area for future research within both scientific and regulatory communities. The crustaceans are ubiquitous in aquatic ecosystems, comprising greater than 66,000 species of ecological and commercial importance. This paper aims to assess the available literature of radiation-induced effects within this subphylum and identify knowledge gaps. A literature search was conducted pertaining to radiation effects on four endpoints as stipulated by a number of regulatory bodies: mortality, morbidity, reproduction and mutation. A major finding of this review was the paucity of data regarding the effects of environmentally relevant radiation doses on crustacean biology. Extremely few studies utilising chronic exposure durations or wild populations were found across all four endpoints. The dose levels at which effects occur was found to vary by orders of magnitude thus presenting difficulties in developing phyla-specific benchmark values and reference levels for radioprotection. Based on the limited data, mutation was found to be the most sensitive endpoint of radiation exposure, with mortality the least sensitive

  9. Enhanced Biological Phosphorus Removal: Metabolic Insights and Salinity Effects

    NARCIS (Netherlands)

    Welles, L.

    2015-01-01

    Enhanced biological phosphorus removal (EBPR) is a biological process for efficient phosphate removal from wastewaters through intracellular storage of polyphosphate by polyphosphate-accumulating organisms (PAO) and subsequent removal of PAO from the system through wastage of sludge. In comparison t

  10. The effect of network biology on drug toxicology

    DEFF Research Database (Denmark)

    Gautier, Laurent; Taboureau, Olivier; Audouze, Karine Marie Laure

    2013-01-01

    it with bioinformatics. With this approach, the assessment of chemical safety can be done across multiple scales of complexity from molecular to cellular and system levels in human health. Network biology can be used at several levels of complexity. Areas covered: This review describes the strengths and limitations......Introduction: The high failure rate of drug candidates due to toxicity, during clinical trials, is a critical issue in drug discovery. Network biology has become a promising approach, in this regard, using the increasingly large amount of biological and chemical data available and combining...... of network biology. The authors specifically assess this approach across different biological scales when it is applied to toxicity. Expert opinion: There has been much progress made with the amount of data that is generated by various omics technologies. With this large amount of useful data, network...

  11. Occurrence and Potential Biological Effects of Amphetamine on Stream Communities.

    Science.gov (United States)

    Lee, Sylvia S; Paspalof, Alexis M; Snow, Daniel D; Richmond, Erinn K; Rosi-Marshall, Emma J; Kelly, John J

    2016-09-06

    The presence of pharmaceuticals, including illicit drugs in aquatic systems, is a topic of environmental significance because of their global occurrence and potential effects on aquatic ecosystems and human health, but few studies have examined the ecological effects of illicit drugs. We conducted a survey of several drug residues, including the potentially illicit drug amphetamine, at 6 stream sites along an urban to rural gradient in Baltimore, Maryland, U.S.A. We detected numerous drugs, including amphetamine (3 to 630 ng L(-1)), in all stream sites. We examined the fate and ecological effects of amphetamine on biofilm, seston, and aquatic insect communities in artificial streams exposed to an environmentally relevant concentration (1 μg L(-1)) of amphetamine. The amphetamine parent compound decreased in the artificial streams from less than 1 μg L(-1) on day 1 to 0.11 μg L(-1) on day 22. In artificial streams treated with amphetamine, there was up to 45% lower biofilm chlorophyll a per ash-free dry mass, 85% lower biofilm gross primary production, 24% greater seston ash-free dry mass, and 30% lower seston community respiration compared to control streams. Exposing streams to amphetamine also changed the composition of bacterial and diatom communities in biofilms at day 21 and increased cumulative dipteran emergence by 65% and 89% during the first and third weeks of the experiment, respectively. This study demonstrates that amphetamine and other biologically active drugs are present in urban streams and have the potential to affect both structure and function of stream communities.

  12. Examining the Effect of Multiple Writing Tasks on Year 10 Biology Students' Understandings of Cell and Molecular Biology Concepts

    Science.gov (United States)

    Hand, Brian; Hohenshell, Liesl; Prain, Vaughan

    2007-01-01

    This paper reports on a study that examined the cumulative effects on students' learning of science, and perceptions of the role of writing in learning, when the students engaged in multiple writing tasks with planning strategy support. The study was conducted with Year 10 biology students who completed two consecutive units on Cells and Molecular…

  13. Determining environmental causes of biological effects: the need for a mechanistic physiological dimension in conservation biology

    OpenAIRE

    Seebacher, Frank; Craig E. Franklin

    2012-01-01

    The emerging field of Conservation Physiology links environmental change and ecological success by the application of physiological theory, approaches and tools to elucidate and address conservation problems. Human activity has changed the natural environment to a point where the viability of many ecosystems is now under threat. There are already many descriptions of how changes in biological patterns are correlated with environmental changes. The next important step is to determine the causa...

  14. Relative Biological Effectiveness and Peripheral Damage of Antiproton Annihilation

    CERN Multimedia

    Kavanagh, J N; Kaiser, F; Tegami, S; Schettino, G; Kovacevic, S; Hajdukovic, D; Welsch, C P; Currell, F J; Toelli, H T; Doser, M; Holzscheiter, M; Herrmann, R; Timson, D J; Alsner, J; Landua, R; Knudsen, H; Comor, J; Moller, S P; Beyer, G

    2002-01-01

    The use of ions to deliver radiation to a body for therapeutic purposes has the potential to be significant improvement over the use of low linear energy transfer (LET) radiation because of the improved energy deposition profile and the enhanced biological effects of ions relative to photons. Proton therapy centers exist and are being used to treat patients. In addition, the initial use of heavy ions such as carbon is promising to the point that new treatment facilities are planned. Just as with protons or heavy ions, antiprotons can be used to deliver radiation to the body in a controlled way; however antiprotons will exhibit additional energy deposition due to annihilation of the antiprotons within the body. The slowing down of antiprotons in matter is similar to that of protons except at the very end of the range beyond the Bragg peak. Gray and Kalogeropoulos estimated the additional energy deposited by heavy nuclear fragments within a few millimeters of the annihilation vertex to be approximately 30 MeV (...

  15. Biological effectiveness of neutron irradiation on animals and man

    Energy Technology Data Exchange (ETDEWEB)

    Straume, T.

    1982-11-01

    Neutron experiments on a highly radiosensitive in vivo system - oocytes in mice - provide new insight into the nature of the radiosensitive targets of these important cells. With the radiobiological literature as background, neutron data from animals and humans are integrated, and the controversial question of radiation protection standards for neutrons is addressed. Oocyte killing in juvenile mice by 0.43-MeV, /sup 252/Cf-fission, and 15 MeV neutrons, compared with that by /sup 60/Co gamma rays, yields unusually low neutron RBEs (relative biological effectiveness). At 0.1 rad of 0.43-MeV neutrons the RBE is only 1.8, contrasting greatly with values of 100 or more reported at low-doses for other endpoints. In mice just prior to birth, however, when oocytes are less radiosensitive, the neutron RBE is much higher, similar to values for most other mammalian endpoints. This dramatic change in neutron RBE with mouse age (occurring within 2 to 3 days) can be explained as the result of a shift from a less radiosensitive target (presumably nuclear DNA) to a much more radiosensitive one (probably the oocyte plasma membrane). Using various approaches, a value for the neutron Quality Factor (Q, a radiation protection standard) is estimated as 17 (+-100%), much lower than 100 which has been suggested. With the large uncertainty, 17 is not markedly different from the value of 10 presently in general use.

  16. Stochastic Effects in Computational Biology of Space Radiation Cancer Risk

    Science.gov (United States)

    Cucinotta, Francis A.; Pluth, Janis; Harper, Jane; O'Neill, Peter

    2007-01-01

    Estimating risk from space radiation poses important questions on the radiobiology of protons and heavy ions. We are considering systems biology models to study radiation induced repair foci (RIRF) at low doses, in which less than one-track on average transverses the cell, and the subsequent DNA damage processing and signal transduction events. Computational approaches for describing protein regulatory networks coupled to DNA and oxidative damage sites include systems of differential equations, stochastic equations, and Monte-Carlo simulations. We review recent developments in the mathematical description of protein regulatory networks and possible approaches to radiation effects simulation. These include robustness, which states that regulatory networks maintain their functions against external and internal perturbations due to compensating properties of redundancy and molecular feedback controls, and modularity, which leads to general theorems for considering molecules that interact through a regulatory mechanism without exchange of matter leading to a block diagonal reduction of the connecting pathways. Identifying rate-limiting steps, robustness, and modularity in pathways perturbed by radiation damage are shown to be valid techniques for reducing large molecular systems to realistic computer simulations. Other techniques studied are the use of steady-state analysis, and the introduction of composite molecules or rate-constants to represent small collections of reactants. Applications of these techniques to describe spatial and temporal distributions of RIRF and cell populations following low dose irradiation are described.

  17. Effects of Simulated Rare Earth Recycling Wastewaters on Biological Nitrification.

    Science.gov (United States)

    Fujita, Yoshiko; Barnes, Joni; Eslamimanesh, Ali; Lencka, Malgorzata M; Anderko, Andrzej; Riman, Richard E; Navrotsky, Alexandra

    2015-08-18

    Increasing rare earth element (REE) supplies by recycling and expanded ore processing will result in generation of new wastewaters. In some cases, disposal to a sewage treatment plant may be favored, but plant performance must be maintained. To assess the potential effects of such wastewaters on biological treatment, model nitrifying organisms Nitrosomonas europaea and Nitrobacter winogradskyi were exposed to simulated wastewaters containing varying levels of yttrium or europium (10, 50, and 100 ppm), and the extractant tributyl phosphate (TBP, at 0.1 g/L). Y and Eu additions at 50 and 100 ppm inhibited N. europaea, even when virtually all of the REE was insoluble. Provision of TBP with Eu increased N. europaea inhibition, although TBP alone did not substantially alter activity. For N. winogradskyi cultures, Eu or Y additions at all tested levels induced significant inhibition, and nitrification shut down completely with TBP addition. REE solubility was calculated using the previously developed MSE (Mixed-Solvent Electrolyte) thermodynamic model. The model calculations reveal a strong pH dependence of solubility, typically controlled by the precipitation of REE hydroxides but also likely affected by the formation of unknown phosphate phases, which determined aqueous concentrations experienced by the microorganisms.

  18. A stabilised tris(hydroxymethyl)aminomethane adduct in reduced collagen.

    Science.gov (United States)

    Cannon, D J; Davison, P F

    1976-01-01

    The reduction of collagen with sodium [3H] borohydride in the presence of Tris buffer results in the stabilization of a Schiff base adduct which is formed between allysine residues and tris(hydroxymethyl)aminomethane. The reduced, radioactive derivative of this adduct has been identified in hydrolyzates or reduced collagen. It elutes before hydroxylysine on an amino acid analyzer column close to the position of dihydroxylysinonorleucine. Similar artifacts may occur when aldehydes present in or added to proteins react with Tris or other amines prior to reduction.

  19. Chemical and biological oxidative effects of carbon black nanoparticles.

    Science.gov (United States)

    Koike, Eiko; Kobayashi, Takahiro

    2006-11-01

    Several studies show that ultrafine particles have a larger surface area than coarse particles, thus causing a greater inflammatory response. In this study, we investigated chemical and biological oxidative effects of nanoparticles in vitro. Carbon black (CB) nanoparticles with mean aerodynamic diameters of 14, 56, and 95nm were examined. The innate oxidative capacity of the CB nanoparticles was measured by consumption of dithiothreitol (DTT) in cell-free system. The expression of heme oxygenase-1 (HO-1) in rat alveolar type II epithelial cell line (SV40T2) and alveolar macrophages (AM) exposed to CB nanoparticles was measured by ELISA. DTT consumption of 14nm CB was higher than that of other CB nanoparticles having the same particle weight. However, DTT consumption was directly proportional to the particle surface area. HO-1 protein in SV40T2 cells was significantly increased by the 14nm and 56nm CB, however, 95nm CB did not affect. HO-1 protein in AM was significantly increased by the 14, 56, and 95nm CB. The increase in HO-1 expression was diminished by N-acetyl-l-cysteine (NAC) treatment of each CB nanoparticles before exposure although the difference between the effects of NAC-treated and untreated 14nm CB did not achieve significant. In conclusion, CB nanoparticles have innate oxidative capacity that may be dependent on the surface area. CB nanoparticles can induce oxidative stress in alveolar epithelial cells and AM that is more prominent with smaller particles. The oxidative stress may, at least partially, be mediated by surface function of particles.

  20. Tea polyphenols, their biological effects and potential molecular targets.

    Science.gov (United States)

    Chen, D; Milacic, V; Chen, M S; Wan, S B; Lam, W H; Huo, C; Landis-Piwowar, K R; Cui, Q C; Wali, A; Chan, T H; Dou, Q P

    2008-04-01

    Tea is the most popular beverage in the world, second only to water. Tea contains an infusion of the leaves from the Camellia sinensis plant rich in polyphenolic compounds known as catechins, the most abundant of which is (-)-EGCG. Although tea has been consumed for centuries, it has only recently been studied extensively as a health-promoting beverage that may act to prevent a number of chronic diseases and cancers. The results of several investigations indicate that green tea consumption may be of modest benefit in reducing the plasma concentration of cholesterol and preventing atherosclerosis. Additionally, the cancer-preventive effects of green tea are widely supported by results from epidemiological, cell culture, animal and clinical studies. In vitro cell culture studies show that tea polyphenols potently induce apoptotic cell death and cell cycle arrest in tumor cells but not in their normal cell counterparts. Green tea polyphenols were shown to affect several biological pathways, including growth factor-mediated pathway, the mitogen-activated protein (MAP) kinase-dependent pathway, and ubiquitin/proteasome degradation pathways. Various animal studies have revealed that treatment with green tea inhibits tumor incidence and multiplicity in different organ sites such as skin, lung, liver, stomach, mammary gland and colon. Recently, phase I and II clinical trials have been conducted to explore the anticancer effects of green tea in humans. A major challenge of cancer prevention is to integrate new molecular findings into clinical practice. Therefore, identification of more molecular targets and biomarkers for tea polyphenols is essential for improving the design of green tea trials and will greatly assist in a better understanding of the mechanisms underlying its anti-cancer activity.

  1. Cytochrome P4501A induction, benzo[a]pyrene metabolism, and nucleotide adduct formation in fish hepatoma cells: Effect of preexposure to 3,3',4,4',5-pentachlorobiphenyl

    Science.gov (United States)

    Smeets, J.M.W.; Voormolen, A.; Tillitt, D.E.; Everaarts, J.M.; Seinen, W.; Vanden Berg, M.D.

    1999-01-01

    In PLHC-1 hepatoma cells, benzo[a]pyrene (B[a]P) caused a maximum induction of cytochrome P4501A (CYP1A) activity, measured as ethoxyresorufin O-deethylation (EROD), after 4 to 8 h of exposure, depending on the B[a]P concentration. The decline of EROD activity at longer exposure times was probably caused by the rapid metabolism of B[a]P in this system (57% metabolism within 4 h incubation). In subsequent experiments, PLHC-1 cells were preinduced with PCB 126 for 24 h and then received a dose of 10, 100, or 1,000 nM 3H-B[a]P. A 1-nM concentration of PCB 126 caused an 80-fold induction of CYP1A activity, resulting in an increase in B[a]P metabolism of less than 10%, except at the highest concentration of B[a]P (1,000 nM), where a 50% increase was observed. In another experiment, an 80-fold induction of CYP1A activity caused a 20% increase in the metabolism of B[a]P (100 nM), and RNA adduct formation was increased approximately twofold. These results indicate that, at exposure concentrations up to 100 nM B[a]P, CYP1A activity is not rate limiting for B[a]P metabolism. Furthermore, CYP1A seems to also he specifically involved in B[a]P activation in PLHC-1 cells. However, CYP1A induction causes only a relatively small increase in activation, probably because of the action of other enzymes involved in B[a]P activation and deactivation.

  2. DNA and protein adducts in human tissues resulting from exposure to tobacco smoke

    OpenAIRE

    Phillips, David H.; Venitt, Stan

    2012-01-01

    Tobacco smoke contains a variety of genotoxic carcinogens that form adducts with DNA and protein in the tissues of smokers. Not only are these biochemical events relevant to the carcinogenic process, but the detection of adducts provides a means of monitoring exposure to tobacco smoke. Characterization of smoking-related adducts has shed light on the mechanisms of smoking-related diseases and many different types of smoking-derived DNA and protein adducts have been identified. Such approaches...

  3. UNUSUALLY STABLE ADDUCT BETWEEN METHANOLYZED AMOXICILLIN OR AMPICILLIN AND THEIR DIKETOPIPERAZINE DERIVATIVES.

    Science.gov (United States)

    Kosińska, Katarzyna; Frański, Rafał; Frańska, Magdalena

    2016-01-01

    Amoxicillin and ampicillin were subjected to methanolysis. As expected, the methanolysis products were observed by HPLC-ESI-MS. Besides these products, diketopiperazine derivatives were also detected. Additionally, unusually stable adduct formed between the products of methanolysis and diketopiperazine derivatives was also identified. Analogical adducts were detected when ethanolysis was performed instead of methanolysis. HPLC-ESI-MS analysis of the separated adducts confirmed that the adducts were composed of methanolysis products and diketopiperazine derivatives.

  4. Plasma and liver acetaminophen-protein adduct levels in mice after acetaminophen treatment: Dose–response, mechanisms, and clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    McGill, Mitchell R.; Lebofsky, Margitta [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Norris, Hye-Ryun K.; Slawson, Matthew H. [Center for Human Toxicology, University of Utah, Salt Lake City, UT (United States); Bajt, Mary Lynn; Xie, Yuchao; Williams, C. David [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Wilkins, Diana G.; Rollins, Douglas E. [Center for Human Toxicology, University of Utah, Salt Lake City, UT (United States); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

    2013-06-15

    At therapeutic doses, acetaminophen (APAP) is a safe and effective analgesic. However, overdose of APAP is the principal cause of acute liver failure in the West. Binding of the reactive metabolite of APAP (NAPQI) to proteins is thought to be the initiating event in the mechanism of hepatotoxicity. Early work suggested that APAP-protein binding could not occur without glutathione (GSH) depletion, and likely only at toxic doses. Moreover, it was found that protein-derived APAP-cysteine could only be detected in serum after the onset of liver injury. On this basis, it was recently proposed that serum APAP-cysteine could be used as diagnostic marker of APAP overdose. However, comprehensive dose–response and time course studies have not yet been done. Furthermore, the effects of co-morbidities on this parameter have not been investigated. We treated groups of mice with APAP at multiple doses and measured liver GSH and both liver and plasma APAP-protein adducts at various timepoints. Our results show that protein binding can occur without much loss of GSH. Importantly, the data confirm earlier work that showed that protein-derived APAP-cysteine can appear in plasma without liver injury. Experiments performed in vitro suggest that this may involve multiple mechanisms, including secretion of adducted proteins and diffusion of NAPQI directly into plasma. Induction of liver necrosis through ischemia–reperfusion significantly increased the plasma concentration of protein-derived APAP-cysteine after a subtoxic dose of APAP. While our data generally support the measurement of serum APAP-protein adducts in the clinic, caution is suggested in the interpretation of this parameter. - Highlights: • Extensive GSH depletion is not required for APAP-protein binding in the liver. • APAP-protein adducts appear in plasma at subtoxic doses. • Proteins are adducted in the cell and secreted out. • Coincidental liver injury increases plasma APAP-protein adducts at subtoxic doses

  5. The Effects of Ultrasound on Biological Systems: Site

    Science.gov (United States)

    El-Karmi, Anan M.

    vs. 18 minutes). This demonstrates that the biological effects of ultrasound are influenced by Ca^ {2+}. The larger increases in G _{rm t} and the time constants confirm other studies addressing the role of Ca ^{2+} in potentiating lipid peroxidation by free radicals, and the role of calcium ions in the formation of tight junctions.

  6. 40 CFR 721.465 - Alkoxylated alkylpolyol acrylates, adduct with alkylamine (generic).

    Science.gov (United States)

    2010-07-01

    ..., adduct with alkylamine (generic). 721.465 Section 721.465 Protection of Environment ENVIRONMENTAL... Significant New Uses for Specific Chemical Substances § 721.465 Alkoxylated alkylpolyol acrylates, adduct with... substances identified generically as alkoxylated alkylpolyol acrylates, adduct with alkylamine (PMNs...

  7. 40 CFR 721.1850 - Toluene sulfonamide bis-phe-nol A epoxy adduct.

    Science.gov (United States)

    2010-07-01

    ... epoxy adduct. 721.1850 Section 721.1850 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.1850 Toluene sulfonamide bis-phe-nol A epoxy adduct. (a) Chemical... as toluene sulfonamide bisphenol A epoxy adduct (PMN P-90-113) is subject to reporting under...

  8. Environmental, Dietary, Maternal, and Fetal Predictors of Bulky DNA Adducts in Cord Blood

    DEFF Research Database (Denmark)

    Pedersen, Marie; Mendez, Michelle A; Schoket, Bernadette

    2015-01-01

    BACKGROUND: Bulky DNA adducts reflect genotoxic exposures, have been associated with lower birth weight, and may predict cancer risk. OBJECTIVE: We selected factors known or hypothesized to affect in utero adduct formation and repair and examined their associations with adduct levels in neonates....

  9. Penetration and propagation into biological matter and biological effects of high-power ultra-wideband pulses: a review.

    Science.gov (United States)

    Schunck, Thérèse; Bieth, François; Pinguet, Sylvain; Delmote, Philippe

    2016-01-01

    Systems emitting ultra-wideband high power microwave (HP/UWB) pulses are developed for military and civilian applications. HP/UWB pulses typically have durations on the order of nanoseconds, rise times of picoseconds and amplitudes around 100 kV m(-1). This article reviews current research on biological effects from HP/UWB exposure. The different references were classified according to endpoints (cardiovascular system, central nervous system, behavior, genotoxicity, teratology …). The article also reviews the aspects of mechanisms of interactions and tissue damage as well as the numerical work that has been done for studying HP/UWB pulse propagation and pulse energy deposition inside biological tissues. The mechanisms proposed are the molecular conformation change, the modification of chemical reaction rates, membrane excitation and breakdown and direct electrical forces on cells or cell constituents, and the energy deposition. As regards the penetration of biological matter and the deposited energy, mainly computations were published. They have shown that the EM field inside the biological matter is strongly modified compared to the incident EM field and that the energy absorption for HP/UWB pulses occurs in the same way as for continuous waves. However, the energy carried by a HP/UWB pulse is very low and the deposited energy is low. The number of published studies dealing with the biological effects is small and only a few pointed out slight effects. It should be further noted that the animal populations used in the studies were not always large, the statistical analyses not always relevant and the teams involved in this research rather limited in number.

  10. Countermeasures for Space Radiation Induced Malignancies and Acute Biological Effects

    Science.gov (United States)

    Kennedy, Ann

    The hypothesis being evaluated in this research program is that control of radiation induced oxidative stress will reduce the risk of radiation induced adverse biological effects occurring as a result of exposure to the types of radiation encountered during space travel. As part of this grant work, we have evaluated the protective effects of several antioxidants and dietary supplements and observed that a mixture of antioxidants (AOX), containing L-selenomethionine, N-acetyl cysteine (NAC), ascorbic acid, vitamin E succinate, and alpha-lipoic acid, is highly effective at reducing space radiation induced oxidative stress in both in vivo and in vitro systems, space radiation induced cytotoxicity and malignant transformation in vitro [1-7]. In studies designed to determine whether the AOX formulation could affect radiation induced mortality [8], it was observed that the AOX dietary supplement increased the 30-day survival of ICR male mice following exposure to a potentially lethal dose (8 Gy) of X-rays when given prior to or after animal irradiation. Pretreatment of animals with antioxidants resulted in significantly higher total white blood cell and neutrophil counts in peripheral blood at 4 and 24 hours following exposure to doses of 1 Gy and 8 Gy. Antioxidant treatment also resulted in increased bone marrow cell counts following irradiation, and prevented peripheral lymphopenia following 1 Gy irradiation. Supplementation with antioxidants in irradiated animals resulted in several gene expression changes: the antioxidant treatment was associated with increased Bcl-2, and decreased Bax, caspase-9 and TGF-β1 mRNA expression in the bone marrow following irradiation. These results suggest that modulation of apoptosis may be mechanistically involved in hematopoietic system radioprotection by antioxidants. Maintenance of the antioxidant diet was associated with improved recovery of the bone marrow following sub-lethal or potentially lethal irradiation. Taken together

  11. Essential Oils from Thyme (Thymus vulgaris): Chemical Composition and Biological Effects in Mouse Model.

    Science.gov (United States)

    Vetvicka, Vaclav; Vetvickova, Jana

    2016-12-01

    Thymus species are popular spices and contain volatile oils as main chemical constituents. Recently, plant-derived essential oils are gaining significant attention due to their significant biological activities. Seven different thymus-derived essential oils were compared in our study. First, we focused on their chemical composition, which was followed up by testing their effects on phagocytosis, cytokine production, chemotaxis, edema inhibition, and liver protection. We found limited biological activities among tested oils, with no correlation between composition and biological effects. Similarly, no oils were effective in every reaction. Based on our data, the tested biological use of these essential oils is questionable.

  12. Triphosgene mediated chlorination of Baylis-Hillman adducts

    Indian Academy of Sciences (India)

    Narender Reddy Thatikonda; Naga Sesha Sai Pavan Kumar Chebolu; Mahendar Budde; Jayathirtha Rao Vaidya

    2012-03-01

    An efficient method for the preparation of allyl chlorides from Baylis-Hillman adducts has been developed using triphosgene/pyridine system. This method is best illustrated by its advantages like operational simplicity, excellent yields, short reaction time, simple procedure and stereoselectivity.

  13. EMG evaluation of hip adduction exercises for soccer players

    DEFF Research Database (Denmark)

    Serner, Andreas; Jakobsen, Markus Due; Andersen, Lars Louis

    2014-01-01

    for the adductor longus during eight hip adduction strengthening exercises and peak EMG was normalised (nEMG) using an isometric maximal voluntary contraction (MVC) as reference. Furthermore, muscle activation of the gluteus medius, rectus abdominis and the external abdominal obliques was analysed during...

  14. SOME SULFATO ADDUCTS AND DERIVATIVE: SYNTHESIS AND SPECTROSCOPIC STUDY

    Directory of Open Access Journals (Sweden)

    MOUHAMADOU BIRAME DIOP

    2014-11-01

    Full Text Available Three new adducts and derivative have been synthesized and studied by infrared and NMR spectroscopies. The suggested structures are discrete with a sulfate behaving as a monochelating, bichelating or monodentate ligand, the environments around the tin centre being octahedral or pentagonal bipyramidal. In all the studied compounds, proposed supramolecular architectures may be obtained when intermolecular hydrogen bonds are considered.

  15. Effect of Organic Solvents and Biologically Relevant Ions on the Light-Induced DNA Cleavage by Pyrene and Its Amino and Hydroxy Derivatives

    Directory of Open Access Journals (Sweden)

    Hongtao Yu

    2002-09-01

    Full Text Available Abstract: Polycyclic aromatic hydrocarbons (PAHs are a class of carcinogenic compounds that are both naturally and artificially produced. Many PAHs are pro-carcinogens that require metabolic activation. Recently, it has been shown that PAH can induce DNA single strand cleavage and formation of PAH-DNA covalent adduct upon irradiation with UVA light. The light-induced DNA cleavage parallels phototoxicity in one instance. The DNA photocleavage efficiency depends on the structure of the PAHs. This article reports the effect of both organic solvents and the presence of biologically relevant ions, Na+, Mg2+, Ca2+, K+, Fe3+, Cu2+, Zn+2, Mn2+, and I-, on the light-induced DNA cleavage by pyrene, 1-hydroxypyrene and 1-aminopyrene. Since both 1-hydroxypyrene (0.6 μM and 1-aminopyrene (6 μM dissolve well in the minimum organic solvents used (2% methanol, dimethylsulfoxide, and dimethylformamide, increasing the amount of the organic solvent resulted in the decrease of the amount of DNA single strand cleavage caused by the combination effect of 1-hydroxy or 1-aminopyrene and UVA light. The result with the less watersoluble pyrene shows that increase of the amount of the organic solvent can increase the amount of DNA single strand DNA photocleavage cause by the combination of pyrene and UVA light. Therefore, there are two effects by the organic solvents: (i to dissolve PAH and (ii to quench DNA photocleavage. The presence of Fe3+ and Zn2+ enhances, while the presence of Ca2+ and Mn2+ inhibits the DNA photocleavage caused by 1-aminopyrene and UVA light. Other metal ions have minimal effect. This means that the effect of ions on DNA photocleavage by PAHs is complex. The presence of KI enhances DNA photocleavage. This indicates that the triplet-excited state of 1-aminopyrene is involved in causing DNA cleavage

  16. Effect of Process-Oriented Guided-Inquiry Learning on Non-majors Biology Students' Understanding of Biological Classification

    Science.gov (United States)

    Wozniak, Breann M.

    The purpose of this study was to examine the effect of process-oriented guided-inquiry learning (POGIL) on non-majors college biology students' understanding of biological classification. This study addressed an area of science instruction, POGIL in the non-majors college biology laboratory, which has yet to be qualitatively and quantitatively researched. A concurrent triangulation mixed methods approach was used. Students' understanding of biological classification was measured in two areas: scores on pre and posttests (consisting of 11 multiple choice questions), and conceptions of classification as elicited in pre and post interviews and instructor reflections. Participants were Minnesota State University, Mankato students enrolled in BIOL 100 Summer Session. One section was taught with the traditional curriculum (n = 6) and the other section in the POGIL curriculum (n = 10) developed by the researcher. Three students from each section were selected to take part in pre and post interviews. There were no significant differences within each teaching method (p vs. M = 7.330 +/- .330; z =-1.729, p = .084) and the traditional group may have scored higher on the pretest than the posttest (M = 8.333 +/- .333 vs M = 7.333 +/- .333; z = -1.650 , p = .099). Two themes emerged after the interviews and instructor reflections: 1) After instruction students had a more extensive understanding of classification in three areas: vocabulary terms, physical characteristics, and types of evidence used to classify. Both groups extended their understanding, but only POGIL students could explain how molecular evidence is used in classification. 2) The challenges preventing students from understanding classification were: familiar animal categories and aquatic habitats, unfamiliar organisms, combining and subdividing initial groupings, and the hierarchical nature of classification. The POGIL students were the only group to surpass these challenges after the teaching intervention. This

  17. Complex relationships between occupation, environment, DNA adducts, genetic polymorphisms and bladder cancer in a case-control study using a structural equation modeling.

    Directory of Open Access Journals (Sweden)

    Stefano Porru

    Full Text Available DNA adducts are considered an integrate measure of carcinogen exposure and the initial step of carcinogenesis. Their levels in more accessible peripheral blood lymphocytes (PBLs mirror that in the bladder tissue. In this study we explore whether the formation of PBL DNA adducts may be associated with bladder cancer (BC risk, and how this relationship is modulated by genetic polymorphisms, environmental and occupational risk factors for BC. These complex interrelationships, including direct and indirect effects of each variable, were appraised using the structural equation modeling (SEM analysis. Within the framework of a hospital-based case/control study, study population included 199 BC cases and 213 non-cancer controls, all Caucasian males. Data were collected on lifetime smoking, coffee drinking, dietary habits and lifetime occupation, with particular reference to exposure to aromatic amines (AAs and polycyclic aromatic hydrocarbons (PAHs. No indirect paths were found, disproving hypothesis on association between PBL DNA adducts and BC risk. DNA adducts were instead positively associated with occupational cumulative exposure to AAs (p = 0.028, whereas XRCC1 Arg 399 (p<0.006 was related with a decreased adduct levels, but with no impact on BC risk. Previous findings on increased BC risk by packyears (p<0.001, coffee (p<0.001, cumulative AAs exposure (p = 0.041 and MnSOD (p = 0.009 and a decreased risk by MPO (p<0.008 were also confirmed by SEM analysis. Our results for the first time make evident an association between occupational cumulative exposure to AAs with DNA adducts and BC risk, strengthening the central role of AAs in bladder carcinogenesis. However the lack of an association between PBL DNA adducts and BC risk advises that these snapshot measurements are not representative of relevant exposures. This would envisage new scenarios for biomarker discovery and new challenges such as repeated measurements at different

  18. Radioprotection, biological effects of the radiations and security in the handling of radioactive material

    CERN Document Server

    Teran, M

    2000-01-01

    The development of the philosophy of the radioprotection is dependent on the understanding of the effects of the radiation in the man. Behind the fact that the radiation is able to produce biological damages there are certain factors with regard to the biological effects of the radiations that determine the boarding of the radioprotection topics.

  19. Radon exposure of the skin: I. Biological effects

    Energy Technology Data Exchange (ETDEWEB)

    Charles, M W [School of Physics and Astronomy, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom)

    2007-09-15

    Radon progeny can plate out on skin and give rise to exposure of the superficial epidermis from alpha emitters Po-218 (7.7 MeV, range {approx}66 {mu}m) and Po-214 (6 MeV, range {approx}44 {mu}m). Dose rates from beta/gamma emitters Pb-214 and Bi-214 are low and only predominate at depths in excess of the alpha range. This paper reviews the evidence for a causal link between exposure from radon and its progeny, and deterministic and stochastic biological effects in human skin. Radiation induced skin effects such as ulceration and dermal atrophy, which require irradiation of the dermis, are ruled out for alpha irradiation from radon progeny because the target cells are considerably deeper than the range of alpha particles. They have not been observed in man or animals. Effects such as erythema and acute epidermal necrosis have been observed in a few cases of very high dose alpha particle exposures in man and after acute high dose exposure in animals from low energy beta radiations with similar depth doses to radon progeny. The required skin surface absorbed doses are in excess of 100 Gy. Such effects would require extremely high levels of radon progeny. They would involve quite exceptional circumstances, way outside the normal range of radon exposures in man. There is no definitive identification of the target cells for skin cancer induction in animals or man. The stem cells in the basal layer which maintain the epidermis are the most plausible contenders for target cells. The majority of these cells are near the end of the range of radon progeny alpha particles, even on the thinnest body sites. The nominal depth of these cells, as recommended by the International Commission on Radiological Protection (ICRP), is 70 {mu}m. There is evidence however that some irradiation of the hair follicles and/or the deeper dermis, as well as the inter-follicular epidermis, is also necessary for skin cancer induction. Alpha irradiation of rodent skin that is restricted to the

  20. Therapy-induced carboplatin-DNA adduct levels in human ovarian tumours in relation to assessment of adduct measurement in mouse tissues.

    Science.gov (United States)

    Jarvis, Ian W H; Meczes, Emma L; Thomas, Huw D; Edmondson, Richard J; Veal, Gareth J; Boddy, Alan V; Ottley, Christopher J; Pearson, D Graham; Tilby, Michael J

    2012-01-01

    Despite an increasing understanding of the molecular mechanisms by which platinum drug DNA adducts interact with cellular processes, the relationship between adduct formation in tumours and clinical response remains unclear. We have determined carboplatin-DNA adduct levels in biopsies removed from ovarian cancer patients following treatment. Reliability of DNA adduct measurements in tissues samples were assessed using experimental animals. Platinum-DNA adduct levels were measured using inductively coupled plasma mass spectrometry (ICP-MS) and plasma drug concentrations determined by atomic absorption spectrometry (AAS). Adduct levels in tissues and plasma pharmacokinetics were determined in Balb/c mice exposed to platinum drugs. Comparisons of adduct levels in tumour and normal tissue were made in nu/nu mice carrying human neuroblastoma xenografts. At 30 min post-cisplatin administration, adduct levels in DNA from kidney and liver were approximately 10- and 6-fold higher than spleen or tumour. By 60 min, levels in liver and kidney, but not spleen or tumour, had fallen considerably. Carboplatin showed high adduct levels only in kidney. Adduct levels in tumour xenografts were comparable to those induced in vitro with similar drug exposures. In clinical samples removed 6h after drug administration, adduct levels ranged from 1.9 to 4.3 and 0.2 to 3.6 nmol Pt/g DNA for tumour biopsies and peripheral blood mononuclear cells, respectively. No correlation was apparent between these two data sets. The present results demonstrate that reliable measurements of adducts in clinical tumours are feasible. Future results should provide insight into drug resistance.

  1. Synthesis and characterization of manganese-glycine and copper-glycine adducts

    Directory of Open Access Journals (Sweden)

    Robson Fernandes de Farias

    2002-09-01

    Full Text Available This work reports the synthesis and characterization of adducts of general formula MCl2.ngly, where M= Mn and Cu; n= 2 and 4, and gly= glycine. The manganese adducts were synthesized by dissolution of both, manganese chloride and glycine in water, whereas the copper adducts were obtained by using an alternative solid state synthesis approach. For all adducts, the obtained infrared data shows that the coordination involves the amine nitrogen atom, as well as an oxygen atom of the COO- group. The TG curves for the synthesized adducts exhibit only one mass loss step associated with the release of glycine molecules.

  2. Controlling the Biological Effects of Spermine Using a Synthetic Receptor

    NARCIS (Netherlands)

    Vial, Laurent; Ludlow, R. Frederick; Leclaire, Julien; Pérez-Fernández, Ruth; Otto, Sijbren

    2006-01-01

    Polyamines play an important role in biology, yet their exact function in many processes is poorly understood. Artificial host molecules capable of sequestering polyamines could be useful tools for studying their cellular function. However, designing synthetic receptors with affinities sufficient to

  3. Immunochemical detection of sulfur mustard-adducts with DNA and proteins: Exploratory research on adducts with proteins

    NARCIS (Netherlands)

    Schans, G.P. van der; Noort, D.; Mars-Groenendijk, R.H.; Dijk-Knijnenburg, H.C.M. van; Fidder, A.; Jong, L.P.A. de; Benschop, H.P.

    2000-01-01

    We have developed two modes of a standard operating procedure (SOP) for immunochemical detection of sulfur mustard adducts to DNA in human blood and skin. In the shortened mode data could be generated within 9 h after in vitro exposure of human blood to > 1 μM sulfur mustard. The sensitive mode allo

  4. Synthesis, structure, and reactivity of diazene adducts: isolation of iso-diazene stabilized as a borane adduct.

    Science.gov (United States)

    Reiß, Fabian; Schulz, Axel; Villinger, Alexander

    2014-09-08

    This work describes the synthesis and full characterization of a series of GaCl3 and B(C6 F5 )3 adducts of diazenes R(1) NNR(2) (R(1) =R(2) =Me3 Si, Ph; R(1) =Me3 Si, R(2) =Ph). Trans-PhNNPh forms a stable adduct with GaCl3 , whereas no adduct, but instead a frustrated Lewis acid-base pair is formed with B(C6 F5 )3 . The cis-PhNNPh⋅B(C6 F5 )3 adduct could only be isolated when UV light was used, which triggers the isomerization from trans- to cis-PhNNPh, which provides more space for the bulky borane. Treatment of trans-PhNNSiMe3 with GaCl3 led to the expected trans-PhNNSiMe3 ⋅GaCl3 adduct but the reaction with B(C6 F5 )3 triggered a 1,2-Me3 Si shift, which resulted in the formation of a highly labile iso-diazene, Me3 Si(Ph)NN; stabilized as a B(C6 F5 )3 adduct. Trans-Me3 SiNNSiMe3 forms a labile cis-Me3 SiNNSiMe3 ⋅B(C6 F5 )3 adduct, which isomerizes to give the transient iso-diazene species (Me3 Si)2 NN⋅B(C6 F5 )3 upon heating. Both iso-diazene species insert easily into one BC bond of B(C6 F5 )3 to afford hydrazinoboranes. All new compounds were fully characterized by means of X-ray crystallography, vibrational spectroscopy, CHN analysis, and NMR spectroscopy. All compounds were further investigated by DFT and the bonding situation was assessed by natural bond orbital (NBO) analysis.

  5. Air pollution effects on fetal and child development: a cohort comparison in China.

    Science.gov (United States)

    Tang, Deliang; Li, Ting Yu; Chow, Judith C; Kulkarni, Sanasi U; Watson, John G; Ho, Steven Sai Hang; Quan, Zhang Y; Qu, L R; Perera, Frederica

    2014-02-01

    In Tongliang, China, a coal-fired power plant was the major pollution source until its shutdown in 2004. We enrolled two cohorts of nonsmoking women and their newborns before and after the shutdown to examine the relationship between prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) and fetal and child growth and development. PAHs were used to measure exposure to air pollution generated by the power plant. Using PAH-DNA adduct levels as biomarkers for the biologically effective dose of PAH exposure, we examined whether PAH-DNA adduct levels were associated with birth outcome, growth rate, and neurodevelopment. Head circumference was greater in children of the second cohort, compared with the first (p = 0.001), consistent with significantly reduced levels of cord blood PAH-DNA adducts in cohort II (p < 0.001) and reduced levels of ambient PAHs (p = 0.01).

  6. Detection of Adriamycin-DNA adducts by accelerator mass spectrometry at clinically relevant Adriamycin concentrations.

    Science.gov (United States)

    Coldwell, Kate E; Cutts, Suzanne M; Ognibene, Ted J; Henderson, Paul T; Phillips, Don R

    2008-09-01

    Limited sensitivity of existing assays has prevented investigation of whether Adriamycin-DNA adducts are involved in the anti-tumour potential of Adriamycin. Previous detection has achieved a sensitivity of a few Adriamycin-DNA adducts/10(4) bp DNA, but has required the use of supra-clinical drug concentrations. This work sought to measure Adriamycin-DNA adducts at sub-micromolar doses using accelerator mass spectrometry (AMS), a technique with origins in geochemistry for radiocarbon dating. We have used conditions previously validated (by less sensitive decay counting) to extract [(14)C]Adriamycin-DNA adducts from cells and adapted the methodology to AMS detection. Here we show the first direct evidence of Adriamycin-DNA adducts at clinically-relevant Adriamycin concentrations. [(14)C]Adriamycin treatment (25 nM) resulted in 4.4 +/- 1.0 adducts/10(7) bp ( approximately 1300 adducts/cell) in MCF-7 breast cancer cells, representing the best sensitivity and precision reported to date for the covalent binding of Adriamycin to DNA. The exceedingly sensitive nature of AMS has enabled over three orders of magnitude increased sensitivity of Adriamycin-DNA adduct detection and revealed adduct formation within an hour of drug treatment. This method has been shown to be highly reproducible for the measurement of Adriamycin-DNA adducts in tumour cells in culture and can now be applied to the detection of these adducts in human tissues.

  7. Preparation and Characterization of Ester from Rosin Acrylic Acid Adduct and Hydroxyethyl Methacrylate

    Institute of Scientific and Technical Information of China (English)

    C.L.Yu; F.A.Zhang

    2007-01-01

    1 Results Rosin is a sort of important renewable resources,which is a foremost product of our country forestry. It has very important meaning to modify the rosin based on its molecule structure and active group, to develop some deep processing products, and to endure with rosin new characteristic[1]. This work uses the rosin and acrylic acid to form rosin adduct, and then reacted with 2-hydroxyethyl methacrylate (HEMA) to form ester under the different condition. The effect of different ratios with the ...

  8. Biological Effects of Listeriolysin O: Implications for Vaccination

    Directory of Open Access Journals (Sweden)

    K. G. Hernández-Flores

    2015-01-01

    Full Text Available Listeriolysin O (LLO is a thiol-activated cholesterol-dependent pore-forming toxin and the major virulence factor of Listeria monocytogenes (LM. Extensive research in recent years has revealed that LLO exerts a wide array of biological activities, during the infection by LM or by itself as recombinant antigen. The spectrum of biological activities induced by LLO includes cytotoxicity, apoptosis induction, endoplasmic reticulum stress response, modulation of gene expression, intracellular calcium oscillations, and proinflammatory activity. In addition, LLO is a highly immunogenic toxin and the major target for innate and adaptive immune responses in different animal models and humans. Recently, the crystal structure of LLO has been published in detail. Here, we review the structure-function relationship for this fascinating microbial molecule, highlighting the potential uses of LLO in the fields of biomedicine and biotechnology, particularly in vaccination.

  9. Increased micronuclei and bulky DNA adducts in cord blood after maternal exposures to traffic-related air pollution

    DEFF Research Database (Denmark)

    Pedersen, M.; Wichmann, J.; Autrup, H.

    2009-01-01

    Exposure to traffic-related air pollution in urban environment is common and has been associated with adverse human health effects. In utero exposures that result in DNA damage may affect health later in life. Early effects of maternal and in utero exposures to traffic-related air pollution were...... for potential confounders and effect modifiers. For the first time increased bulky DNA adducts and MN in cord blood after maternal exposures to traffic-related air pollution are found, demonstrating that these transplacental environmental exposures induce DNA damage in newborns. Given that increased DNA damage...... umbilical cords, concurrently collected at the time of planned Caesarean section. Modeled residential traffic density, a proxy measure of traffic-related air pollution exposures, was validated by indoor levels of nitrogen dioxide and polycyclic aromatic hydrocarbons in 42 non-smoking homes. DNA adduct...

  10. Nitrated and Brominated Narcotine and its Cleaved Adduct as Butyrylcholinesterase Inhibitors

    Directory of Open Access Journals (Sweden)

    M. A. Abbasi

    2013-09-01

    Full Text Available Narcotine is a very antitussive agent and its modification may lead to some more biological activities. In this presented paper, narcotine (1 was first subjected to nitration and bromination to yield nitrated narcotine (2 and brominated narcotine (3. It was further made to react with phenylchloroformate (6 to give a cleaved addition product 4. This adduct 4 was further nitrated and brominated to yield substituted derivatives 5 and 6, respectively. The structure elucidation of the synthesized compounds was processed via IR, EI-MS and 1H-NMR spectra. These were also screened against butyrylcholinesterase enzyme and were found to the moderate inhibitors of butyrylcholinesterase except nitrated product, 2, of narcotine (1.

  11. Polycyclic aromatic hydrocarbon-DNA adducts in beluga whales from the Arctic.

    Science.gov (United States)

    Mathieu, A; Payne, J F; Fancey, L L; Santella, R M; Young, T L

    1997-05-01

    The Arctic is still relatively pristine in nature, but it is also vulnerable to pollution because contaminants originating from midlatitudes are transported to the Arctic by atmospheric processes, ocean currents, and rivers (Muir et al., 1992). Recognition of this fact of Arctic vulnerability has resulted in a Declaration on the Protection of the Arctic Environment by eight Arctic countries. A manifest aim of this declaration is to develop an Arctic Monitoring and Assessment Program. We report here on the presence of measurable levels of polycyclic aromatic hydrocarbon-DNA adducts, including relatively high levels in Arctic beluga (Delphinapterus leucas). These results lend support to the value of developing biological assessment programs for Arctic wildlife.

  12. Resurrecting the body: Has portmodernism had any effect on biology?

    Science.gov (United States)

    Gilbert, S F

    1995-01-01

    While postmodernism has had very little influence in biology (for reasons discussed in the paper), it can provide a framework for discussing the context in which biology is done. Here, four biological views of the body/self are contrasted: the neural, immunological, genetic, and phenotypic bodies. Each physical view of the body extrapolates into a different model of the body politic, and each posits a different relationship between bodies of knowledge. The neural view of the body models a body politic wherein society is defined by its culture and laws. The genetic view privileges views of polities based on ethnicity and race. The immune body extrapolates into polities that can defend themselves against other such polities. The phenotypic view of the body politic stands in opposition to these three major perspectives and integrates them without giving any predominance. The view of science as a "neural" body of knowledge contends that science is aperspectival and objective. The perspective of the "immune" body is that science exists to defend the interests of its creataors. The genetic view of science is that science is the basis of all culture. The extrapolation of the phenotypic body to science insists upon the utilitarian rationale for scientific interprises. In all instances, the genetic view of the body/body politic/body of science is presently in ascendance.

  13. Integrated monitoring of chemicals and their effects on four sentinel species, Limanda limanda, Platichthys flesus, Nucella lapillus and Mytilus sp., in Seine Bay: A key step towards applying biological effects to monitoring.

    Science.gov (United States)

    Burgeot, Thierry; Akcha, Farida; Ménard, Dominique; Robinson, Craig; Loizeau, Véronique; Brach-Papa, Christophe; Martínez-Gòmez, Concepción; Le Goff, Jérémie; Budzinski, Hélène; Le Menach, Karine; Cachot, Jérome; Minier, Christophe; Broeg, Katja; Hylland, Ketil

    2017-03-01

    The International workshop on Integrated Assessment of CONtaminants impacts on the North sea (ICON) provided a framework to validate the application of chemical and biological assessment thresholds (BACs and EACs) in the Seine Bay in France. Bioassays (oyster larval anomalies, Corophium arenarium toxicity assay and DR Calux) for sediment and biomarkers: ethoxyresorufin-O-deethylase (EROD) activity, acetylcholinesterase (AChE) activity, lysosomal membrane stability (LMS), DNA strand breaks using the Comet assay, DNA adducts, micronucleus (MN), PAH metabolites, imposex, intersex and fish external pathologies were analysed in four marine sentinel species (Platichthys flesus, Limanda limanda, Mytilus sp. and Nucella lapilus). Polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and heavy metals were analysed in biota and sediment. Results for sediment and four species in 2008-2009 made it possible to quantify the impact of contaminants using thresholds (Environmental Assessment Criteria/EAC2008: 70% and EAC2009: 60%) and effects (EAC2008: 50% and EAC2009: 40%) in the Seine estuary. The Seine estuary is ranked among Europe's most highly polluted sites.

  14. Adverse effects of biologics: a network meta-analysis and Cochrane overview

    DEFF Research Database (Denmark)

    Singh, J. A.; Wells, G. A.; Christensen, Robin Daniel Kjersgaard

    2011-01-01

    Background Biologics are used for the treatment of rheumatoid arthritis and many other conditions. While the efficacy of biologics has been established, there is uncertainty regarding the adverse effects of this treatment. Since serious risks such as tuberculosis (TB) reactivation, serious...

  15. Gender Inequality in Biology Classes in China and Its Effects on Students' Short-Term Outcomes

    Science.gov (United States)

    Liu, Ning; Neuhaus, Birgit

    2014-01-01

    This study investigated gender inequality in biology lessons and analysed the effects of the observed inequality on students' short-term knowledge achievement, situational interest and students' evaluation of teaching (SET). Twenty-two biology teachers and 803 7th-grade students from rural and urban classrooms in China participated in the study.…

  16. A Study of the Probe Effect on the Apparent Image of Biological Atomic Force Microscopy

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The probe effect on the apparent image of biological atomic force microscopy was explored in this study, and the potential of AFM in conformational study of gene related biological processes was illustrated by the specific nanostructural information of a new antitumor drug binding to DNA.

  17. Indirect ecological effects in invaded landscapes: Spillover and spillback from biological control agents to native analogues

    Science.gov (United States)

    Biological control remains an effective option for managing large-scale weed problems in natural areas. The predation or parasitism of biological control agents by other species present in the introduced range (biotic resistance) is well studied and is often cited as the cause for a lack of establis...

  18. Biological Effects of TMPRSS2/ERG Fusion Isoforms in Human Prostate Cancer

    Science.gov (United States)

    2009-02-01

    TITLE: Biological Effects of TMPRSS2/ERG Fusion Isoforms in Human Prostate Cancer PRINCIPAL INVESTIGATOR: Jianghua Wang, M.D...6 JAN 2009 / / /4. TITLE AND SUBTITLE Biological Effects of TMPRSS2/ERG Fusion Isoforms in Human Prostate Cancer 5a. CONTRACT NUMBER W81XWH...quantitative RT-PCR arrays we have identified candidate mediators of these phenotypic effects . We propose to extend these studies to primary prostate epithelial

  19. Exposure of bus and taxi drivers to urban air pollutants as measured by DNA and protein adducts

    DEFF Research Database (Denmark)

    Hemminki, K.; Zhang, L.F.; Krüger, J.;

    1994-01-01

    Urinary 1-hydroxypyrene, lymphocyte DNA adducts, serum protein-bound PAH and hemoglobin-bound alkene adducts were analysed from 4 groups of non-smoking men: urban and suburban bus drivers, taxi drivers and suburban controls. The only differences between the groups were in DNA adducts between...... suburban bus drivers and controls, and in DNA adduct and plasma protein PAH-adducts between taxi drivers and controls....

  20. Integrated Network Analysis and Effective Tools in Plant Systems Biology

    Directory of Open Access Journals (Sweden)

    Atsushi eFukushima

    2014-11-01

    Full Text Available One of the ultimate goals in plant systems biology is to elucidate the genotype-phenotype relationship in plant cellular systems. Integrated network analysis that combines omics data with mathematical models has received particular attention. Here we focus on the latest cutting-edge computational advances that facilitate their combination. We highlight (1 network visualization tools, (2 pathway analyses, (3 genome-scale metabolic reconstruction, and (4 the integration of high-throughput experimental data and mathematical models. Multi-omics data that contain the genome, transcriptome, proteome, and metabolome and mathematical models are expected to integrate and expand our knowledge of complex plant metabolisms.

  1. Biological influences on hydrogen effects in steel in seawater

    Energy Technology Data Exchange (ETDEWEB)

    Edyvean, R.G.J.; Benson, J.; Thomas, C.J. [Univ. of Sheffield (United Kingdom). Dept. of Chemical and Process Engineering; Beech, I.B. [Univ. of Portsmouth (United Kingdom). Dept. of Chemistry; Videla, H.A. [Univ. of La Plata (Argentina). Dept. of Chemistry

    1997-08-01

    Conditions conducive to the enhancement of corrosion-fatigue crack growth and of hydrogen embrittlement can be generated by the activity of sulfate-reducing bacterial. However, while the presence of bacteria encourages more hydrogen entry into susceptible metals when compared to similar levels of sulfide generated abiotically, corrosion-fatigue crack growth rates are slower in biological environments than the equivalent abiological environment. These results are discussed in the light of recent findings on the enhancement and inhibition of surface corrosion by bacterial biofilms.

  2. Crystal Structure of Ethanolamine 5-Nitrosalicylic Acid Organic Adduct

    Institute of Scientific and Technical Information of China (English)

    金轶; 车云霞; 魏荣敏; 郑吉民

    2004-01-01

    The title adduct (C18H24N4O12, Mr = 488.41) crystallizes in monoclinic, space group P21/c with a = 4.0514(19), b = 25.193(11), c = 10.751(5)(A), β = 95.070(8)o, V = 1093.0(9)(A)3, Z = 4, Dc = 1.484 g/cm3, F(000) = 512, μ(MoKα) = 1.26 cm-1, T = 293 K, the final R = 0.0593 and wR = 0.0862 for 956 observed reflections with I > 2(I). The compound is a 1:1 adduct of ethanolamine and 5-nitrosalicylic acid. The nitrogen atom of ethanolamine is protonated. In this crystal there exist a number of hydrogen bonds which link the ethanolamine and 5-nitrosalicylic acid molecules to form a three-dimensional infinite network structure.

  3. Diagnosis and dosimetry of exposure to sulfur mustard: Development of a standard operating procedure for mass spectrometric analysis of haemoglobin adducts - Exploratory research on albumin and keratin adducts

    NARCIS (Netherlands)

    Noort, D.; Fidder, A.; Hulst, A.G.; Jong, L.P.A. de; Benschop, H.P.

    2000-01-01

    Experiments were carried out to develop a standard operating procedure for analysis of sulfur mustard adducts to the N-terminal valine in haemoglobin and to explore adduct formation with albumin and keratin. In the first approach, gas chromatography-negative chemical ionization/mass spectrometry (GC

  4. Diagnosis and dosimetry of exposure to sulfur mustard: Development of a standard operating procedure for hemoglobin adducts: Exploratory research on albumin and keratin adducts

    NARCIS (Netherlands)

    Noort, D.; Fidder, A.; Jong, L.P.A. de; Schans, G.P. van der; Benschop, H.P.

    2000-01-01

    A standard operating procedure (SOP) for determination of the sulfur mustard adduct to the N-terminal valine in hemoglobin was developed. By using this SOP, it was found that the Nterminal valine adduct in globin of hairless guinea pigs and marmosets which had been exposed to sulfur mustard (0.5 LD5

  5. Protein tyrosine adduct in humans self-poisoned by chlorpyrifos

    Energy Technology Data Exchange (ETDEWEB)

    Li, Bin, E-mail: binli@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States); Eyer, Peter, E-mail: peter.eyer@lrz.uni-muenchen.de [Walther-Straub-Institut Für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München, 80336 München (Germany); Eddleston, Michael, E-mail: M.Eddleston@ed.ac.uk [Clinical Pharmacology Unit, University of Edinburgh, Edinburgh (United Kingdom); Jiang, Wei, E-mail: wjiang@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States); Schopfer, Lawrence M., E-mail: lmschopf@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States); Lockridge, Oksana, E-mail: olockrid@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States)

    2013-06-15

    Studies of human cases of self-inflicted poisoning suggest that chlorpyrifos oxon reacts not only with acetylcholinesterase and butyrylcholinesterase but also with other blood proteins. A favored candidate is albumin because in vitro and animal studies have identified tyrosine 411 of albumin as a site covalently modified by organophosphorus poisons. Our goal was to test this proposal in humans by determining whether plasma from humans poisoned by chlorpyrifos has adducts on tyrosine. Plasma samples from 5 self-poisoned humans were drawn at various time intervals after ingestion of chlorpyrifos for a total of 34 samples. All 34 samples were analyzed for plasma levels of chlorpyrifos and chlorpyrifos oxon (CPO) as a function of time post-ingestion. Eleven samples were analyzed for the presence of diethoxyphosphorylated tyrosine by mass spectrometry. Six samples yielded diethoxyphosphorylated tyrosine in pronase digests. Blood collected as late as 5 days after chlorpyrifos ingestion was positive for CPO-tyrosine, consistent with the 20-day half-life of albumin. High plasma CPO levels did not predict detectable levels of CPO-tyrosine. CPO-tyrosine was identified in pralidoxime treated patients as well as in patients not treated with pralidoxime, indicating that pralidoxime does not reverse CPO binding to tyrosine in humans. Plasma butyrylcholinesterase was a more sensitive biomarker of exposure than adducts on tyrosine. In conclusion, chlorpyrifos oxon makes a stable covalent adduct on the tyrosine residue of blood proteins in humans who ingested chlorpyrifos. - Highlights: • Chlorpyrifos-poisoned patients have adducts on protein tyrosine. • Diethoxyphosphate-tyrosine does not lose an alkyl group. • Proteins in addition to AChE and BChE are modified by organophosphates.

  6. Ion Pairs or Neutral Molecule Adducts? Cooperativity in Hydrogen Bonding

    Science.gov (United States)

    DeKock, Roger L.; Schipper, Laura A.; Dykhouse, Stephanie C.; Heeringa, Lee P.; Brandsen, Benjamin M.

    2009-01-01

    We performed theoretical studies on the systems NH[subscript 3] times HF times mH[subscript 2]O, NH[subscript 3] times HCl times mH[subscript 2]O, with m = 0, 1, 2, and 6. The molecules with m = 0 form hydrogen-bonded adducts with little tendency to form an ion-pair structure. The molecule NH[subscript 3] times HCl times H[subscript 2]O cannot be…

  7. Fluorescence of Phytochrome Adducts with Synthetic Locked Chromophores*

    OpenAIRE

    Zienicke, Benjamin; Chen, Li-Yi; Khawn, Htoi; Hammam, Mostafa A. S.; Kinoshita, Hideki; Reichert, Johannes; Ulrich, Anne S.; Inomata, Katsuhiko; Lamparter, Tilman

    2010-01-01

    We performed steady state fluorescence measurements with phytochromes Agp1 and Agp2 of Agrobacterium tumefaciens and three mutants in which photoconversion is inhibited. These proteins were assembled with the natural chromophore biliverdin (BV), with phycoerythrobilin (PEB), which lacks a double bond in the ring C-D-connecting methine bridge, and with synthetic bilin derivatives in which the ring C-D-connecting methine bridge is locked. All PEB and locked chromophore adducts are photoinactive...

  8. NEW HYDROGENOXALATO ADDUCTS AND MALONATO COMPLEX: SYNTHESIS AND SPECTROSCOPIC STUDIES

    Directory of Open Access Journals (Sweden)

    MOUHAMADOU BIRAME DIOP

    2014-08-01

    Full Text Available Two new hydrogenoxalato and one malonato adduct and complex have been synthesized and studied by infrared and NMR spectroscopies. The suggested structures are discrete, the hydrogenoxalate behaving as a monodentate ligand or only involved in hydrogen bonding, the environment around the tin (IV centre being tetrahedral or trigonal bipyramidal. The malonate anion is a monodentate ligand. In all the suggested structures, when extra hydrogen bonds are considered, supramolecular architectures are obtained.

  9. SOME NEW SULFONATO ADDUCT: SYNTHESIS AND SPECTROSCOPIC STUDIES

    Directory of Open Access Journals (Sweden)

    MOUHAMADOU BIRAME DIOP

    2015-02-01

    Full Text Available Three new adducts have been synthesized and studied by infrared and NMR spectroscopies. The suggested structures are discrete with a pyridine -3- sulfonate acting as a tri O-chelating and N-donor or as a non σ coordinating ligand, a 4-aminobenzenesulfonate behaving as a monodentate O-donor, the environments around the tin centre being tetrahedral, octahedral or seven coordinated. In all the studied compounds, supramolecular architectures are obtained when hydrogen bonds are considered.

  10. NEW HALO- AND ORGANOTIN (IV PHENYLARSENIATO ADDUCTS AND DERIVATIVES

    Directory of Open Access Journals (Sweden)

    BOCAR TRAORE

    2013-12-01

    Full Text Available Four new phenylarseniato adducts and organotin derivatives have been synthesized and studied by infrared. The suggested structures are polymeric, (SnX4; X = Cl, Br and SnPh3Cl while being discrete for SnPh2Cl(PhAsO3H2isoBu2NH2. When OH- - - Cl, NH - - - O or NH- - -Cl hydrogen bonds are involved, supramolecular architectures are obtained.

  11. Synthesis and selenation of tandem multicomponent condensation adducts

    OpenAIRE

    Hua, Guoxiong; Du, Junyi; Fuller, Amy; Athukorala Arachchige, Kasun Sankalpa; Cordes, David Bradford; Slawin, Alexandra Martha Zoya; Woollins, J. Derek

    2015-01-01

    A number of four-component condensation adducts, which were readily obtained from one-pot reaction of aryl carboxylic acids, arylaldehydes, arylamines and c-hexylisocyanide, were treated with two equivalents of Woollins’ reagent leading to the formation of a series of novel selenoamides with one or two C=Se groups, or heterocyclic compounds such as 1,3-selenazole and 1,3-selenazolidin-5-one Postprint Peer reviewed

  12. NEW HYDROGENOXALATO ADDUCTS AND MALONATO COMPLEX: SYNTHESIS AND SPECTROSCOPIC STUDIES

    OpenAIRE

    2014-01-01

    Two new hydrogenoxalato and one malonato adduct and complex have been synthesized and studied by infrared and NMR spectroscopies. The suggested structures are discrete, the hydrogenoxalate behaving as a monodentate ligand or only involved in hydrogen bonding, the environment around the tin (IV) centre being tetrahedral or trigonal bipyramidal. The malonate anion is a monodentate ligand. In all the suggested structures, when extra hydrogen bonds are considered, supramolecular architectures are...

  13. PHOSPHATO AND PHOSPHONATO ADDUCTS: SYNTHESIS AND SPECTROSCOPIC STUDY

    Directory of Open Access Journals (Sweden)

    Mouhamadou Birame Diop

    2014-05-01

    Full Text Available Two new adducts have been synthesized and studied by infrared and NMR spectroscopy. The suggested structures are discrete or of infinite chain type with a phosphate behaving as a bidentate ligand, a phosphonate acting as a monodentate ligand, the environments around the tin centre being tetrahedral or trigonal bipyramidal. In all the studied compounds, supramolecular architectures are obtained when hydrogen bonds are considered.

  14. Detection of Radical Adducts with Small Molecular Weights by Matrix-Assisted Laser Desorption/Ionization with Fourier Transform Mass Spectrometry

    Institute of Scientific and Technical Information of China (English)

    TIAN,Yao-Wei; SUN,Shi-Hao; XIE,Jian-Ping; ZONG,Yong-Li; NIE,Cong; GUO,Yin-Long

    2007-01-01

    As an alternative method, matrix-assisted laser desorption/ionization with Fourier transform mass spectrometry (MALDI-FTMS) has been successfully used to detect and identify free radical adducts with small molecular weights of hydroxyl and 2-cyano-2-propyl radicals trapped with 5,5-dimethylpyrroline N-oxide (DMPO). The detection and identification by MS/MS experiments using sustained offresonance irradiation collision-induced dissociation (SORI-CID) of [(DMPO+·OH-·H)+H+] (m/z 130.0868) and [DMPO+2 ·CH(CH3)2CN+H+] (m/z 250.1917) have demonstrated that MALDI-FTMS could be an effective method for detection and identification of free radical adducts. Other radical adducts have been also detected and identified. The approach of MALDI-FTMS is simple, fast, and sensitive which has potential for high-throughput analysis.

  15. Bulky DNA Adducts in Cord Blood, Maternal Fruit-and-Vegetable Consumption, and Birth Weight in a European Mother-Child Study (NewGeneris)

    DEFF Research Database (Denmark)

    Pedersen, Marie; Schoket, Bernadette; Godschalk, Roger W

    2013-01-01

    Background: Tobacco-smoke, airborne, and dietary exposures to polycyclic aromatic hydrocarbons (PAHs) have been associated with reduced prenatal growth. Evidence from biomarker-based studies of low-exposed populations is limited. Bulky DNA adducts in cord blood reflect the prenatal effective dose...... with those with high intake (-58 g; 95% CI: -206, 90 g)Conclusions: Maternal exposure to genotoxic agents that induce the formation of bulky DNA adducts may affect intrauterine growth. Maternal fruit and vegetable consumption may be protective.Citation: Pedersen M, Schoket B, Godschalk RW, Wright J, von......, Kleinjans JC, Segerbäck D, Kogevinas M. 2013. Bulky DNA adducts in cord blood, maternal fruit-and-vegetable consumption, and birth weight in a European mother-child study (NewGeneris). Environ Health Perspect 121:1200-1206; http://dx.doi.org/10.1289/ehp.1206333....

  16. Biological effects of an impulse current according to laboratory researches of electroshock devices

    Directory of Open Access Journals (Sweden)

    Grigoryev О.A.

    2013-12-01

    Full Text Available The federal law "About Weapons" permits the use of electroshock devices if they are safe for people. We developed requirements for the procedure medical-biological testing on the safety of electroshock devices. We did an experimental study assessing medical-biological safety of electroshock devices. The assessment is based on a point system, which use ranges of biological effects. The experiments were performed in rabbits. We used 13 electroshock devices with different characteristics. Electroshock devices were made in Russia. We found that the response of a biological object to inrush current included convulsions, respiratory and cardiac activity. We analyzed the biological effects of pulsed current electroshock device obtained in experimental conditions. It is concluded that the characteristic clinical and physiological response to the action of electric current is pulsepolyparametric and depending on a combination of characteristics and condition of the electric impulse influence object.

  17. Effects of Oxidative Stress on Mesenchymal Stem Cell Biology

    Science.gov (United States)

    2016-01-01

    Mesenchymal stromal/stem cells (MSCs) are multipotent stem cells present in most fetal and adult tissues. Ex vivo culture-expanded MSCs are being investigated for tissue repair and immune modulation, but their full clinical potential is far from realization. Here we review the role of oxidative stress in MSC biology, as their longevity and functions are affected by oxidative stress. In general, increased reactive oxygen species (ROS) inhibit MSC proliferation, increase senescence, enhance adipogenic but reduce osteogenic differentiation, and inhibit MSC immunomodulation. Furthermore, aging, senescence, and oxidative stress reduce their ex vivo expansion, which is critical for their clinical applications. Modulation of sirtuin expression and activity may represent a method to reduce oxidative stress in MSCs. These findings have important implications in the clinical utility of MSCs for degenerative and immunological based conditions. Further study of oxidative stress in MSCs is imperative in order to enhance MSC ex vivo expansion and in vivo engraftment, function, and longevity. PMID:27413419

  18. Biological methanogenesis and the CO2 greenhouse effect

    Science.gov (United States)

    Guthrie, P. D.

    1986-01-01

    It is well established that plants tend to increase net photosynthesis under increased carbon dioxide. It is also well established that a large fraction of atmospheric methane is produced by microbial metabolism of organic sediments in paddies and freshwater wetlands, where a major source of organic debris is local plant growth. As CO2 increases, it may lead to increased methane production and a resulting enhancement of the expected greenhouse warming. A rough estimate of the present rate of this biologically mediated feedback on the climate system indicates that it might account for as much as 30 percent of the observed methane increase and speed up the greenhouse forcing by as much as 15 percent.

  19. Dehydroepiandrosterone biosynthesis, metabolism, biological effects, and clinical use (analytical review

    Directory of Open Access Journals (Sweden)

    N. P. Goncharov

    2015-04-01

    Full Text Available The review presents the fundamental information on the metabolism of dehydroepiandrosterone (DHEA, its biological role and possibilities of its use for replacement therapy. There were studied species differences in the synthesis of DHEA in the adrenal cortex. It was found that DHEA and DHEA-sulfate are produced only by the adrenal glands of humans and monkeys, including lower monkeys. Their biosynthesis involves the following steps: cholesterol → pregnenolone → 17-hydroxypregnenolone → DHEA. The adrenal glands of other species, including rats and mice do not synthesize DHEA. At the same time, in certain brain structures not only in man and monkey, but also in other animals DHEA and its precursors are synthesized de novo which are denoted as neurosteroids. It was demonstrated that Purkinje cells which play an important role in memory formation and learning are mainly place neurosteroid formation in mammals and other vertebrates. To establish the relationship of age and the level of DHEA and other steroids we studied the dynamics of their levels at different periods of postnatal development of people. Peak concentration DHEA observed in aged 25–30 years. In the interval from 20 to 90 years in humans the level falls approximately for 90 %. Cortisol levels in blood does not vary with age, leading to an imbalance in the ratio of cortisol/DHEA. Proved a major role of DHEA as a source (precursor for the synthesis of biologically active sex steroids – testosterone, estradiol and estrone in peripheral tissues. This review presents the bioavailability of DHEA in various physiological and pathological processes in humans and animals. In animal experiments has shown a higher bioavailability of DHEA in transdermal administration as compared with oral administration as in this case there is no steroid rapid inactivation in the liver during its first passage. According to recent studies there is a pronounced dependence of bioavailability of DHEA

  20. Dehydroepiandrosterone biosynthesis, metabolism, biological effects, and clinical use (analytical review

    Directory of Open Access Journals (Sweden)

    N. P. Goncharov

    2015-01-01

    Full Text Available The review presents the fundamental information on the metabolism of dehydroepiandrosterone (DHEA, its biological role and possibilities of its use for replacement therapy. There were studied species differences in the synthesis of DHEA in the adrenal cortex. It was found that DHEA and DHEA-sulfate are produced only by the adrenal glands of humans and monkeys, including lower monkeys. Their biosynthesis involves the following steps: cholesterol → pregnenolone → 17-hydroxypregnenolone → DHEA. The adrenal glands of other species, including rats and mice do not synthesize DHEA. At the same time, in certain brain structures not only in man and monkey, but also in other animals DHEA and its precursors are synthesized de novo which are denoted as neurosteroids. It was demonstrated that Purkinje cells which play an important role in memory formation and learning are mainly place neurosteroid formation in mammals and other vertebrates. To establish the relationship of age and the level of DHEA and other steroids we studied the dynamics of their levels at different periods of postnatal development of people. Peak concentration DHEA observed in aged 25–30 years. In the interval from 20 to 90 years in humans the level falls approximately for 90 %. Cortisol levels in blood does not vary with age, leading to an imbalance in the ratio of cortisol/DHEA. Proved a major role of DHEA as a source (precursor for the synthesis of biologically active sex steroids – testosterone, estradiol and estrone in peripheral tissues. This review presents the bioavailability of DHEA in various physiological and pathological processes in humans and animals. In animal experiments has shown a higher bioavailability of DHEA in transdermal administration as compared with oral administration as in this case there is no steroid rapid inactivation in the liver during its first passage. According to recent studies there is a pronounced dependence of bioavailability of DHEA

  1. Sequestration of mitochondrial iron by silica particles initiates a biological effect.

    Science.gov (United States)

    Summary Inhalation of particulate matter has presented a challenge to human health for thousands of years. The underlying mechanism for biological effect following particle exposure is incompletely understood. We tested the postulate that particle sequestration of cell and mit...

  2. Glyphosate accumulation, translocation, and biological effects in Coffea arabica after single and multiple exposures

    DEFF Research Database (Denmark)

    Schrübbers, Lars Christoph; Valverde, Bernal E.; Strobel, Bjarne W.

    2016-01-01

    . In this study, we investigated glyphosate translocation over time, and its concentration and biological effects after single and multiple simulated spray-drift exposures. Additionally, shikimic acid/glyphosate ratios were used as biomarkers for glyphosate binding to its target enzyme.Four weeks after...... of application, however, was more important regarding biological effects than the number of applications both in the greenhouse and in the field. In the field, berry yield, the most important biological response variable, was reduced 26% by the first out of four sequential applications of glyphosate at 64 g a...

  3. Professional development strategies for teaching urban biology teachers to use concept maps effectively

    Science.gov (United States)

    McGregor Petgrave, Dahlia M.

    Many teachers are not adequately prepared to help urban students who have trouble understanding conceptual ideas in biology because these students have little connection to the natural world. This study explored potential professional development strategies to help urban biology teachers use concept maps effectively with various topics in the biology curriculum. A grounded theory approach was used to develop a substantive professional development model for urban biology teachers. Qualitative data were collected through 16 semi-structured interviews of professional developers experienced in working with concept maps in the urban context. An anonymous online survey was used to collect quantitative data from 56 professional developers and teachers to support the qualitative data. The participants were from New York City, recruited through the NY Biology-Chemistry Professional Development Mentor Network and the NY Biology Teachers' Association. According to the participants, map construction, classroom applications, lesson planning, action research, follow-up workshops, and the creation of learning communities are the most effective professional development strategies. The interviewees also proposed English language learning strategies such as picture maps, native word maps, and content reading materials with underlined words. This study contributes to social change by providing a professional development model to use in planning workshops for urban teachers. Urban teachers improve their own conceptual understanding of biology while learning how to implement concept mapping strategies in the classroom. Students whose teachers are better prepared to teach biology in a conceptual manner have the potential of growing into more scientifically literate citizens.

  4. Bioaccumulation and biological effects in the earthworm Eisenia fetida exposed to natural and depleted uranium

    Energy Technology Data Exchange (ETDEWEB)

    Giovanetti, Anna, E-mail: anna.giovanetti@enea.i [ENEA, Institute of Radiation Protection, CR Casaccia Via Anguillarese 301, 00123 Rome (Italy); Fesenko, Sergey [International Atomic Energy Agency (IAEA), Agency' s Laboratories Seibersdorf, A-2444 Seibersdorf (Austria); Cozzella, Maria L. [ENEA, National Institute for Metrology of Ionizing Radiation, CR Casaccia Via Anguillarese 301, 00123 Rome (Italy); Asencio, Lisbet D. [Centro de Estudios Ambientales, Carretera a Castillo de Jagua, CP. 59350 C. Nuclear, Cienfuegos (Cuba); Sansone, Umberto [International Atomic Energy Agency (IAEA), Agency' s Laboratories Seibersdorf, A-2444 Seibersdorf (Austria)

    2010-06-15

    The accumulations of both natural (U) and depleted (DU) uranium in the earthworms (Eisenia fetida) were studied to evaluate corresponding biological effects. Concentrations of metals in the experimental soil ranged from 1.86 to 600 mg kg{sup -1}. Five biological endpoints: mortality, animals' weight increasing, lysosomal membrane stability by measuring the neutral red retention time (the NRRT), histological changes and genetic effects (Comet assay) were used to evaluate biological effects in the earthworms after 7 and 28 days of exposure. No effects have been observed in terms of mortality or weight reduction. Cytotoxic and genetic effects were identified at quite low U concentrations. For some of these endpoints, in particular for genetic effects, the dose (U concentration)-effect relationships have been found to be non-linear. The results have also shown a statistically significant higher level of impact on the earthworms exposed to natural U compared to depleted U.

  5. Zinc acetylacetonate hydrate adducted with nitrogen donor ligands: Synthesis, spectroscopic characterization, and thermal analysis

    Science.gov (United States)

    Brahma, Sanjaya; Shivashankar, S. A.

    2015-12-01

    We report synthesis, spectroscopic characterization, and thermal analysis of zinc acetylacetonate complex adducted by nitrogen donor ligands, such as pyridine, bipyridine, and phenanthroline. The pyridine adducted complex crystallizes to monoclinic crystal structure, whereas other two adducted complexes have orthorhombic structure. Addition of nitrogen donor ligands enhances the thermal property of these complexes as that with parent metal-organic complex. Zinc acetylacetonate adducted with pyridine shows much higher volatility (106 °C), decomposition temperature (202 °C) as that with zinc acetylacetonate (136 °C, 220 °C), and other adducted complexes. All the adducted complexes are thermally stable, highly volatile and are considered to be suitable precursors for metal organic chemical vapor deposition. The formation of these complexes is confirmed by powder X-ray diffraction, Fourier transform infrared spectroscopy, mass spectroscopy, and elemental analysis. The complexes are widely used as starting precursor materials for the synthesis of ZnO nanostructures by microwave irradiation assisted coating process.

  6. Hydrolytic Cleavage Products of Globin Adducts in Urine as Possible Biomarkers of Cumulative Dose: Proof of Concept Using Styrene Oxide as a Model Adduct-Forming Compound.

    Science.gov (United States)

    Mráz, Jaroslav; Hanzlíková, Iveta; Moulisová, Alena; Dušková, Šárka; Hejl, Kamil; Bednářová, Aneta; Dabrowská, Ludmila; Linhart, Igor

    2016-04-18

    A new experimental model was designed to study the fate of globin adducts with styrene 7,8-oxide (SO), a metabolic intermediate of styrene and a model electrophilic compound. Rat erythrocytes were incubated with SO at 7 or 22 °C. Levels of specific amino acid adducts in globin were determined by LC/MS analysis of the globin hydrolysate, and erythrocytes with known adduct content were administered intravenously to recipient rats. The course of adduct elimination from the rat blood was measured over the following 50 days. In the erythrocytes incubated at 22 °C, a rapid decline in the adduct levels on the first day post-transfusion followed by a slow phase of elimination was observed. In contrast, the adduct elimination in erythrocytes incubated at 7 °C was nearly linear, copying elimination of intact erythrocytes. In the urine of recipient rats, regioisomeric SO adducts at cysteine, valine, lysine, and histidine in the form of amino acid adducts and/or their acetylated metabolites as well as SO-dipeptide adducts were identified by LC/MS supported by synthesized reference standards. S-(2-Hydroxy-1-phenylethyl)cysteine and S-(2-hydroxy-2-phenylethyl)cysteine, the most abundant globin adducts, were excreted predominantly in the form of the corresponding urinary mercapturic acids (HPEMAs). Massive elimination of HPEMAs via urine occurred within the first day from the erythrocytes incubated at both 7 and 22 °C. However, erythrocytes incubated at 7 °C also showed a slow second phase of elimination such that HPEMAs were detected in urine up to 50 days post-transfusion. These results indicate for the first time that globin adducts can be cleaved in vivo to modified amino acids and dipeptides. The cleavage products and/or their predictable metabolites are excreted in urine over the whole life span of erythrocytes. Some of the urinary adducts may represent a new type of noninvasive biomarker for exposure to adduct-forming chemicals.

  7. III. Biological effects of radiation from external and internal sources

    Energy Technology Data Exchange (ETDEWEB)

    Stone, R.S.

    1948-05-24

    This report focuses on the hemotological effects of total body irradiation from external and internal sources observed in patients treated for arthritis with radioactive phosphorus administered intravenously.

  8. Trifluoroacetylated adducts in spermatozoa, testes, liver and plasma and CYP2E1 induction in rats after subchronic inhalatory exposure to halothane.

    Science.gov (United States)

    Oropeza-Hernández, Luis F; Quintanilla-Vega, Betzabet; Reyes-Mejía, Raul A; Serrano, Carmen J; García-Latorre, Ethel A; Dekant, Wolfgang; Manno, Maurizio; Albores, Arnulfo

    2003-09-15

    The induction of cytochrome P450 (CYP) 2E1 in testes and liver and the presence of trifluoroacetylated (TFA) adducts in spermatozoa, testes, liver and plasma were investigated in rats subchronically exposed by inhalation to halothane (15 ppm/4 h/day/5 days/week/9 weeks). After halothane exposure, p-nitrophenol hydroxylase (p-NPH) activity increased 3.2-fold and CYP2E1 apo-protein content 7-fold in testes, whereas in liver, p-NPH increased 2.3-fold and CYP2E1 apoprotein content 1.4-fold. These results suggest a differential inductive effect of halothane on CYP2E1 in these tissues. Moreover, TFA adducts were present in microsomes of testis and liver and in plasma of halothane-treated rats. The immunoblot analysis of testicular microsomes showed two intense TFA protein bands of 63 and 59 kDa, whereas in liver three intense bands of 100, 76 and 63 kDa were observed. Bands of similar molecular weights to those observed in liver were detected in the plasma of halothane-treated animals. In addition, TFA adducts were detected by immunofluorescence in spermatozoa, probably in the acrosome and/or perinuclear theca region, and in the distal tail of spermatozoa. The increase in CYP2E1 apoprotein and p-NPH activity observed in testis and liver microsomes suggests that halothane induces its own biotransformation both hepatically and extrahepatically and in addition, that the nature of the TFA adducts will depend on the proteins present in each tissue. Also, the presence of TFA adducts in spermatozoa may result from the activation of halothane in the reproductive tract. The detailed mechanism of TFA adduct formation and its consequences on the spermatozoa function remain to be fully clarified.

  9. DNA adducts and PM(10) exposure in traffic-exposed workers and urban residents from the EPIC-Florence City study.

    Science.gov (United States)

    Palli, Domenico; Saieva, Calogero; Munnia, Armelle; Peluso, Marco; Grechi, Daniele; Zanna, Ines; Caini, Saverio; Decarli, Adriano; Sera, Francesco; Masala, Giovanna

    2008-09-15

    Air pollution and particulate matter in urban areas have been associated with increased mortality from cardiovascular and respiratory diseases and increased cancer risk. Carcinogenic effects of particulate matter have been related to the contents of specific compounds, such as polycyclic aromatic hydrocarbons. The latter may form bulky DNA adducts, that may be considered as candidate markers of cancer risk. We have recently shown that traffic-exposed workers and the general population in Florence have divergent levels of DNA adducts, possibly related to different levels of exposure to genotoxic agents from vehicle emissions. In the current study, in a series of 214 Florence City healthy adults enrolled in a prospective study in the period 1993-1998 (152 residents / 62 traffic-exposed workers), we investigated the correlation between individual levels of DNA bulky adducts and PM(10) exposure scores based on daily environmental measures provided by the local Environmental Protection Agency for the whole study period, by two types of urban monitoring stations (high- and low-traffic). We found that PM(10) cumulative scores from high-traffic stations over the last 1-2 weeks prior to blood drawing significantly correlated (r=0.58, p=0.02) with DNA adduct levels among non-smoking traffic-exposed workers (but not among residents with no occupational exposure to vehicle emissions). A multivariate regression analysis adjusted for possible confounders confirmed these findings. PM(10) scores from low-traffic stations did not show any correlation. These results show that DNA adduct levels in non-smoking workers reflect the average levels of exposure to PM(10) in high-traffic urban areas experienced over a time period of 1-2 weeks. Since DNA adduct levels have been found predictive of lung cancer risk, our findings provide clues relevant to the reduction of genotoxic damage and possibly cancer risk among traffic-exposed urban workers.

  10. Aflatoxin-albumin adduct formation after single and multiple doses of aflatoxin B(1) in rats treated with Thai medicinal plants.

    Science.gov (United States)

    Vinitketkumnuen, U; Chewonarin, T; Dhumtanom, P; Lertprasertsuk, N; Wild, C P

    1999-07-16

    The objective was to conduct an assessment of the ability of two Thai medicinal plants, Cymbopogon citratus Stapf and Murdannia loriformis, to modulate levels of serum aflatoxin-albumin (AF-albumin) adducts following aflatoxin B(1) (AFB(1)) exposure in rats. The influence of the plant extracts on AF-albumin adduct formation after a single exposure to 250 microg/kg body weight (bw) AFB(1) was measured over a 48-h period. Rats received M. loriformis extract (3 g/kg bw) or C. citratus Stapf extract (5 g/kg bw) daily for the week prior to the AFB(1) administration. In control rats, maximum adduct levels were observed 12 h post-AFB(1) treatment but in the animals receiving Murdannia extract, maximum levels occurred earlier, at 4 h post-treatment. No such effect was observed with the Cymbopogon extract. Daily treatment of rats with AFB(1) at 250 microg/kg bw for 3 weeks caused serum AF-albumin adduct levels to accumulate over a 10-14 day period and reach plateau levels 4.4-fold higher than observed after a single dose. Treatment with Murdannia extract for 1 week before and then throughout the AFB(1) exposure period resulted in a slight decrease in the AF-albumin adduct levels in the first week of the intervention. After that time, however, the reduction in adduct levels in the Murdannia extract group did not differ significantly from controls. No significant alteration in the biomarker levels was seen with the Cymbopogon extract treatments compared to control rats.

  11. Soil degradation effect on biological activity in Mediterranean calcareous soils

    Science.gov (United States)

    Roca-Pérez, L.; Alcover-Sáez, S.; Mormeneo, S.; Boluda, R.

    2009-04-01

    Soil degradation processes include erosion, organic matter decline, compaction, salinization, landslides, contamination, sealing and biodiversity decline. In the Mediterranean region the climatological and lithological conditions, together with relief on the landscape and anthropological activity are responsible for increasing desertification process. It is therefore considered to be extreme importance to be able to measure soil degradation quantitatively. We studied soil characteristics, microbiological and biochemical parameters in different calcareous soil sequences from Valencia Community (Easter Spain), in an attempt to assess the suitability of the parameters measured to reflect the state of soil degradation and the possibility of using the parameters to assess microbiological decline and soil quality. For this purpose, forest, scrubland and agricultural soil in three soil sequences were sampled in different areas. Several sensors of the soil biochemistry and microbiology related with total organic carbon, microbial biomass carbon, soil respiration, microorganism number and enzyme activities were determined. The results show that, except microorganism number, these parameters are good indicators of a soil biological activity and soil quality. The best enzymatic activities to use like indicators were phosphatases, esterases, amino-peptidases. Thus, the enzymes test can be used as indicators of soil degradation when this degradation is related with organic matter losses. There was a statistically significant difference in cumulative O2 uptake and extracellular enzymes among the soils with different degree of degradation. We would like to thank Spanish government-MICINN for funding and support (MICINN, project CGL2006-09776).

  12. Colorimetric and fluorescent detection of biological thiols in aqueous solution

    Institute of Scientific and Technical Information of China (English)

    Yin-Hui Li; Jin-Feng Yang; Chang-Hui Liu; Ji-Shan Li; Rong-Hua Yang

    2013-01-01

    A new colorimetric and fluorescent probe,2-(2,4-dinitrostyryl)-1,3,3-trimethyl-3H-indolium iodide (DTI),for selective and sensitive detection of biological thiols is reported.In aqueous solution at physiological pH 7.4,biological thiols react with DTI via Michael addition to give the brownish red adduct concomitant with fluorescence emission decrease.

  13. Tissue distribution of DNA adducts and their persistence in blood of mice exposed to benzene.

    OpenAIRE

    Li, G.; Wang, C.; Xin, W. (Weidong); Yin, S

    1996-01-01

    Chemicals combine with DNA, resulting in DNA damage, which could initiate carcinogenesis. To study whether benzene or benzene metabolites bind to DNA, DNA adducts in various tissues and their persistence in leukocytes were examined using the 32P-postlabeling assay. LACA mice were dosed ip with benzene at 500 mg/kg bw twice for 5 days. Two additional spots of DNA adducts are formed in bone marrow cells, liver cells, and peripheral blood compared with control mice. The relative adduct labeling ...

  14. Detection and quantification of 4-ABP adducts in DNA from bladder cancer patients.

    Science.gov (United States)

    Zayas, Beatriz; Stillwell, Sara W; Wishnok, John S; Trudel, Laura J; Skipper, Paul; Yu, Mimi C; Tannenbaum, Steven R; Wogan, Gerald N

    2007-02-01

    We analyzed bladder DNA from 27 cancer patients for dG-C8-4-aminobiphenyl (dG-C8-ABP) adducts using the liquid chromatography tandem mass spectrometry method with a 700 attomol (1 adduct in 10(9) bases) detection limit. Hemoglobin (Hb) 4-aminobiphenyl (4-ABP) adduct levels were measured by gas chromatography-mass spectrometry. After isolation of dG-C8-ABP by immunoaffinity chromatography and further purification, deuterated (d9) dG-C8-ABP (MW=443 Da) was added to each sample. Structural evidence and adduct quantification were determined by selected reaction monitoring, based on the expected adduct ion [M+H+]+1, at m/z 435 with fragmentation to the product ion at m/z 319, and monitoring of the transition for the internal standard, m/z 444-->328. The method was validated by analysis of DNA (100 microg each) from calf thymus; livers from ABP-treated and untreated rats; human placentas; and TK6 lymphoblastoid cells. Adduct was detected at femtomol levels in DNA from livers of ABP-treated rats and calf thymus, but not in other controls. The method was applied to 41 DNA samples (200 microg each) from 27 human bladders; 28 from tumor and 14 from surrounding non-tumor tissue. Of 27 tissues analyzed, 44% (12) contained 5-80 dG-C8-ABP adducts per 10(9) bases; only 1 out of 27 (4%) contained adduct in both tumor and surrounding tissues. The Hb adduct was detected in samples from all patients, at levels of 12-1960 pg per gram Hb. There was no correlation between levels of DNA and Hb adducts. The presence of DNA adducts in 44% of the subjects and high levels of Hb adducts in these non-smokers indicate environmental sources of exposure to 4-ABP.

  15. Detection and characterization of human serum antibodies to polycyclic aromatic hydrocarbon diol-epoxide DNA adducts.

    OpenAIRE

    Newman, M J; Light, B A; Weston, A; Tollurud, D; Clark, J L; Mann, D L; Blackmon, J P; Harris, C C

    1988-01-01

    The presence of serum antibodies to the diol-epoxide DNA adducts of representative polycyclic aromatic hydrocarbons (PAH), chrysene, benz[a]anthracene and benzo[a]pyrene, was determined by ELISA using serum samples obtained from normal healthy individuals. Antibodies that reacted against PAH adducted-DNA, but not against PAH-adducted protein, were found in the serum of approximately 40% of the test individuals. Specificity analysis of the antibodies demonstrated that serological cross-reactio...

  16. The biological effects of five feline IFN-alpha subtypes.

    Science.gov (United States)

    Baldwin, Susan L; Powell, Tim D; Sellins, Karen S; Radecki, Steven V; Cohen, J John; Milhausen, Michael J

    2004-06-01

    IFN-alpha has been shown to induce both antiviral and antiproliferative activities in animals. This report describes the biological activity of five recently identified feline IFN-alpha subtypes expressed in the Chinese hamster ovary (CHO) cell line (rfeIFN-alpha1[CHO], rfeIFN-alpha2[CHO], rfeIFN-alpha3[CHO], rfeIFN-alpha5[CHO] and rfeIFN-alpha6[CHO]) and the feIFN-alpha6 subtype expressed in and purified from Pichia pastoris (rfeIFN-alpha6[P. pastoris]). The rfeIFN-alpha[CHO] subtypes were tested for antiviral activity against either Vesicular stomatitis virus (VSV) or feline calicivirus (FCV) infected feline embryonic fibroblast cell line (AH927) or Crandell feline kidney cell line (CRFK). Antiviral activity was induced against both VSV and FCV infected AH927 cells and VSV infected CRFK cells by all five of the rfeIFN-alpha[CHO] subtypes and rfeIFN-alpha6[P. pastoris]. In addition, the IFN-alpha inducible Mx gene (associated with antiviral activity) was upregulated in vivo 24 h following treatment with rfeIFN-alpha6[P. pastoris], compared to baseline levels seen prior to treatment. All of the rfeIFN-alpha[CHO] subtypes and rfeIFN-alpha6[P. pastoris] exhibited antiproliferative activity in the FeT-J cell line (an IL-2 independent feline T-cell line). Both necrosis and apoptosis were observed in rfeIFN-alpha6[P. pastoris]-treated FeT-J cells. The rfeIFN-alpha3[CHO] subtype consistently exhibited lower antiviral and antiproliferative activity compared to that observed with the other four rfeIFN-alpha[CHO] subtypes. In summary, this paper demonstrates that five previously described feIFN-alpha subtypes induce both antiviral and antiproliferative activities in vitro and are capable of upregulating the feMx gene in vivo.

  17. Psychological Effects towards Humans Living in the Environment Made of Biological Concrete in Malaysia at 2015

    Directory of Open Access Journals (Sweden)

    Amirreza Talaiekhozani

    2017-01-01

    Full Text Available In day-to-day life concrete become a compulsory material in the construction field as to make it a real concern among researchers for producing concrete with improved properties. Biological method is one of the new methods to improve concrete properties. Although, much research about biological concrete has been carried out, but till now nobody has not studied for the psychological effects of using a house or offices made up of biological concrete. The aim of this study is to investigate and find out the person's opinion about staying in a house or offices made up of biological concrete. In this study, a questionnaire containing eight questions was prepared and distributed among 21 persons in Malaysia University of Technology including students, academic and non-academic staffs among which few of them was an expert in the field of biological concrete and others did not have any knowledge about the bioconcrete. Finally, the results obtained from the questionnaires were analyzed. The results showed that 81% of participants in this study would like to stay in a house or office made up of biological concrete. However, 38% of participants believe that staying in a house or office made of biological concrete can cause health related problems. The current research paper can be considered significant for architects and civil engineers to have the insight to look into the psychological aspects of using biological concrete for various applications in the field of construction.

  18. Correlation between Quadriceps Endurance and Adduction Moment in Medial Knee Osteoarthritis.

    Directory of Open Access Journals (Sweden)

    Soon-Hyuck Lee

    Full Text Available It is not clear whether the strength or endurance of thigh muscles (quadriceps and hamstring is positively or negatively correlated with the adduction moment of osteoarthritic knees. This study therefore assessed the relationships between the strength and endurance of the quadriceps and hamstring muscles and adduction moment in osteoarthritic knees and evaluated predictors of the adduction moment. The study cohort comprised 35 patients with unilateral medial osteoarthritis and varus deformity who were candidates for open wedge osteotomy. The maximal torque (60°/sec and total work (180°/sec of the quadriceps and hamstring muscles and knee adduction moment were evaluated using an isokinetic testing device and gait analysis system. The total work of the quadriceps (r = 0.429, P = 0.037 and hamstring (r = 0.426, P = 0.045 muscles at 180°/sec each correlated with knee adduction moment. Preoperative varus deformity was positively correlated with adduction moment (r = 0.421, P = 0.041. Multiple linear regression analysis showed that quadriceps endurance at 180°/sec was the only factor independently associated with adduction moment (β = 0.790, P = 0.032. The adduction moment of osteoarthritic knees correlated with the endurance, but not the strength, of the quadriceps muscle. However, knee adduction moment did not correlate with the strength or endurance of the hamstring muscle.

  19. N7-guanine adducts of the epoxy metabolites of 1,3-butadiene in mice lung.

    Science.gov (United States)

    Koivisto, P; Peltonen, K

    2001-06-01

    Epoxy metabolites of 1,3-butadiene are electrophilic and can bind to nucleophilic sites in DNA forming DNA adducts. In this study, guanine N7 adducts of epoxy butene and guanine N7 adducts of epoxy butanediol were measured in lung tissues of mice inhalation exposed to various concentrations of 1,3-butadiene. 32P-postlabeling of DNA adducts were used to demonstrate that the DNA adducts derived from epoxybutene and epoxybutanediol were formed in a dose dependent manner. More than 98% of all adducts detected were formed from epoxybutanediol. Enantiomeric distribution of the adducts formed in vivo differs from that of in vitro experiments demonstrated before. In the case of epoxybutene most of the adducts were formed to the terminal carbon of the S-epoxybutene enantiomer. Most of the adducts derived from epoxybutanediol were formed from the 2S-3R enantiomer. The data demonstrates that enzymatic processes involved with activation and/or detoxification of the metabolites are enantiospecific and/or DNA repair machinery repairs the damage with stereochemical considerations. These are the crucial factors if interspecies differences in tumor sensitiveness is concerned.

  20. Synthesis and Characterization of the Adducts of Bis(O-ethyldithiocarbonatocopper(II with Substituted Pyridines

    Directory of Open Access Journals (Sweden)

    Gurpreet Kour

    2013-01-01

    Full Text Available Monomeric five coordinated adducts of bis(O-ethyldithiocarbonatocopper(II of general formula [Cu(C2H5OCS22(L], [L = 2-, 3-, 4-methylpyridines and 2-, 3-, 4-ethylpyridines] have been synthesized and characterized by elemental analysis, i.r. and electronic spectroscopy, magnetic and conductivity measurements. Analytical results show that the adducts have 1 : 1 stoichiometry. The adducts were found to be paramagnetic and their magnetic moments at room temperature lie within the 1.81–1.94 B.M. range and this indicates the presence of one unpaired electron. All the adducts have distorted square pyramidal geometry.

  1. Temporal and spatial features of the formation of DNA adducts in sulfur mustard-exposed skin

    Energy Technology Data Exchange (ETDEWEB)

    Batal, Mohamed [Laboratoire «Lésions des Acides Nucléiques», Université Joseph Fourier – Grenoble 1, CEA/Institut Nanoscience et Cryogénie/SCIB, UMR-E3, Grenoble (France); Département de Toxicologie et Risques Chimiques, Unité de Brûlure Chimique, Institut de Recherche Biomédicale des Armées, Antenne de La Tronche (France); Boudry, Isabelle; Mouret, Stéphane; Wartelle, Julien; Emorine, Sandy; Bertoni, Marine [Département de Toxicologie et Risques Chimiques, Unité de Brûlure Chimique, Institut de Recherche Biomédicale des Armées, Antenne de La Tronche (France); Bérard, Izabel [Laboratoire «Lésions des Acides Nucléiques», Université Joseph Fourier – Grenoble 1, CEA/Institut Nanoscience et Cryogénie/SCIB, UMR-E3, Grenoble (France); Cléry-Barraud, Cécile [Département de Toxicologie et Risques Chimiques, Unité de Brûlure Chimique, Institut de Recherche Biomédicale des Armées, Antenne de La Tronche (France); and others

    2013-12-15

    Sulfur mustard (SM) is a chemical warfare agent that targets skin where it induces large blisters. DNA alkylation is a critical step to explain SM-induced cutaneous symptoms. We determined the kinetics of formation of main SM–DNA adducts and compare it with the development of the SM-induced pathogenesis in skin. SKH-1 mice were exposed to 2, 6 and 60 mg/kg of SM and treated skin was biopsied between 6 h and 21 days. Formation of SM DNA adducts was dose-dependent with a maximum immediately after exposure. However, adducts were persistent and still detectable 21 days post-exposure. The time-dependent formation of DNA adducts was also found to be correlated with the appearance of apoptotic cells. This temporal correlation suggests that these two early events are responsible for the severity of the damage to the skin. Besides, SM–DNA adducts were also detected in areas located next to contaminated zone, thus suggesting that SM diffuses in skin. Altogether, this work provides for the first time a clear picture of SM-induced genotoxicity using DNA adducts as a marker. - Highlights: • Sulfur mustard adducts are formed in DNA after skin exposure. • DNA damage formation is an early event in the pathological process of skin burn. • The amount of SM–DNA adducts is maximal at the earliest time point investigated. • Adducts are still detected 3 weeks after exposure. • Sulfur mustard diffuses in skin especially when large doses are applied.

  2. MICROWAVE SYSTEM FOR RESEARCH BIOLOGICAL EFFECTS ON LABORATORY ANIMALS

    OpenAIRE

    Kopylov, Alexei; Kruglik, Olga; Khlebopros, Rem

    2014-01-01

    This research is concerned with development of the microwave system for research the radiophysical microwave radiation effects on laboratory animals. The frequency was 1 GHz. The results obtained demonstrate the metabolic changes in mice under the electromagnetic field influence.

  3. Protection by quercetin and quercetin-rich fruit juice against induction of oxidative DNA damage and formation of BPDE-DNA adducts in human lymphocytes

    NARCIS (Netherlands)

    Wilms, L.C.; Hollman, P.C.H.; Boots, A.W.; Kleinjans, J.C.S.

    2005-01-01

    Flavonoids are claimed to protect against cardiovascular disease, certain forms of cancer and ageing, possibly by preventing initial DNA damage. Therefore, we investigated the protective effects of the flavonoid quercetin against the formation of oxidative DNA damage and bulky DNA adducts in human l

  4. Ion mobility studies of carbohydrates as group I adducts: isomer specific collisional cross section dependence on metal ion radius.

    Science.gov (United States)

    Huang, Yuting; Dodds, Eric D

    2013-10-15

    Carbohydrates play numerous critical roles in biological systems. Characterization of oligosaccharide structures is essential to a complete understanding of their functions in biological processes; nevertheless, their structural determination remains challenging in part due to isomerism. Ion mobility spectrometry provides the means to resolve gas phase ions on the basis of their shape-to-charge ratios, thus providing significant potential for separation and differentiation of carbohydrate isomers. Here, we report on the determination of collisional cross sections for four groups of isomeric carbohydrates (including five isomeric disaccharides, four isomeric trisaccharides, two isomeric pentasaccharides, and two isomeric hexasaccharides) as their group I metal ion adducts (i.e., [M + Li](+), [M + Na](+), [M + K](+), [M + Rb](+), and [M + Cs](+)). In all, 65 collisional cross sections were measured, the great majority of which have not been previously reported. As anticipated, the collisional cross sections of the carbohydrate metal ion adducts generally increase with increasing metal ion radius; however, the collisional cross sections were found to scale with the group I cation size in isomer specific manners. Such measurements are of substantial analytical value, as they illustrate how the selection of charge carrier influences carbohydrate ion mobility determinations. For example, certain pairs of isomeric carbohydrates assume unique collisional cross sections upon binding one metal ion, but not another. On the whole, these data suggest a role for the charge carrier as a probe of carbohydrate structure and thus have significant implications for the continued development and application of ion mobility spectrometry for the distinction and resolution of isomeric carbohydrates.

  5. A theoretical framework for biological control of soil-borne plant pathogens: Identifying effective strategies.

    Science.gov (United States)

    Cunniffe, Nik J; Gilligan, Christopher A

    2011-06-07

    We develop and analyse a flexible compartmental model of the interaction between a plant host, a soil-borne pathogen and a microbial antagonist, for use in optimising biological control. By extracting invasion and persistence thresholds of host, pathogen and biological control agent, performing an equilibrium analysis, and numerical investigation of sensitivity to parameters and initial conditions, we determine criteria for successful biological control. We identify conditions for biological control (i) to prevent a pathogen entering a system, (ii) to eradicate a pathogen that is already present and, if that is not possible, (iii) to reduce the density of the pathogen. Control depends upon the epidemiology of the pathogen and how efficiently the antagonist can colonise particular habitats (i.e. healthy tissue, infected tissue and/or soil-borne inoculum). A sharp transition between totally effective control (i.e. eradication of the pathogen) and totally ineffective control can follow slight changes in biologically interpretable parameters or to the initial amounts of pathogen and biological control agent present. Effective biological control requires careful matching of antagonists to pathosystems. For preventative/eradicative control, antagonists must colonise susceptible hosts. However, for reduction in disease prevalence, the range of habitat is less important than the antagonist's bulking-up efficiency.

  6. Replication past the butadiene diepoxide-derived DNA adduct S-[4-(N(6)-deoxyadenosinyl)-2,3-dihydroxybutyl]glutathione by DNA polymerases.

    Science.gov (United States)

    Cho, Sung-Hee; Guengerich, F Peter

    2013-06-17

    1,2,3,4-Diepoxybutane (DEB), a metabolite of the carcinogen butadiene, has been shown to cause glutathione (GSH)-dependent base substitution mutations, especially A:T to G:C mutations in Salmonella typhimurium TA1535 [Cho, S. H., et al. (2010) Chem. Res. Toxicol. 23, 1544] and Escherichia coli TRG8 cells [Cho, S. H., and Guengerich, F. P. (2012) Chem. Res. Toxicol. 25, 1522]. We previously identified S-[4-(N(6)-deoxyadenosinyl)-2,3-dihydroxybutyl]GSH [N(6)dA-(OH)2butyl-GSH] as a major adduct in the reaction of S-(2-hydroxy-3,4-epoxybutyl)glutathione (DEB-GSH conjugate) with nucleosides and calf thymus DNA and in vivo in livers of mice and rats treated with DEB [Cho, S. H., and Guengerich, F. P. (2012) Chem. Res. Toxicol. 25, 706]. For investigation of the miscoding potential of the major DEB-GSH conjugate-derived DNA adduct [N(6)dA-(OH)2butyl-GSH] and the effect of GSH conjugation on replication of DEB, extension studies were performed in duplex DNA substrates containing the site-specifically incorporated N(6)dA-(OH)2butyl-GSH adduct, N(6)-(2,3,4-trihydroxybutyl)deoxyadenosine adduct (N(6)dA-butanetriol), or unmodified deoxyadenosine (dA) by human DNA polymerases (Pol) η, ι, and κ, bacteriophage polymerase T7, and Sulfolobus solfataricus polymerase Dpo4. Although dTTP incorporation was the most preferred addition opposite the N(6)dA-(OH)2butyl-GSH adduct, N(6)dA-butanetriol adduct, or unmodified dA for all polymerases, the dCTP misincorporation frequency opposite N(6)dA-(OH)2butyl-GSH was significantly higher than that opposite the N(6)dA-butanetriol adduct or unmodified dA with Pol κ or Pol T7. LC-MS/MS analysis of full-length primer extension products confirmed that Pol κ or Pol T7 incorporated the incorrect base C opposite the N(6)dA-(OH)2butyl-GSH lesion. These results indicate the relevance of GSH-containing adducts for the A:T to G:C mutations produced by DEB.

  7. Effect of solids retention time and wastewater characteristics on biological phosphorus removal

    DEFF Research Database (Denmark)

    Henze, Mogens; Aspegren, H.; Jansen, J.l.C.

    2002-01-01

    The paper deals with the effect of wastewater, plant design and operation in relation to biological nitrogen and phosphorus removal and the possibilities to model the processes. Two Bio-P pilot plants were operated for 2.5 years in parallel receiving identical wastewater. The plants had SRT of 4...... with time which has importance in relation to modelling. The overall conclusion of the comparison between the two plants is that the biological phosphorus removal efficiency under practical operating conditions is affected by the SRT in the plant and the wastewater composition. Thus great care should...... in verification of models for Nitrogen and Enhanced Biological Phosphorus Removal....

  8. Which chemicals drive biological effects in wastewater and recycled water?

    Science.gov (United States)

    Tang, Janet Y M; Busetti, Francesco; Charrois, Jeffrey W A; Escher, Beate I

    2014-09-01

    Removal of organic micropollutants from wastewater during secondary treatment followed by reverse osmosis and UV disinfection was evaluated by a combination of four in-vitro cell-based bioassays and chemical analysis of 299 organic compounds. Concentrations detected in recycled water were below the Australian Guidelines for Water Recycling. Thus the detected chemicals were considered not to pose any health risk. The detected pesticides in the wastewater treatment plant effluent and partially advanced treated water explained all observed effects on photosynthesis inhibition. In contrast, mixture toxicity experiments with designed mixtures containing all detected chemicals at their measured concentrations demonstrated that the known chemicals explained less than 3% of the observed cytotoxicity and less than 1% of the oxidative stress response. Pesticides followed by pharmaceuticals and personal care products dominated the observed mixture effects. The detected chemicals were not related to the observed genotoxicity. The large proportion of unknown toxicity calls for effect monitoring complementary to chemical monitoring.

  9. Biological effects of lysophosphatidic acid in the nervous system.

    Science.gov (United States)

    Frisca, Frisca; Sabbadini, Roger A; Goldshmit, Yona; Pébay, Alice

    2012-01-01

    Lysophosphatidic acid (LPA) is a bioactive lipid that regulates a broad range of cellular effects in various cell types, leading to a variety of responses in tissues, including in the nervous system. LPA and its receptors are found in the nervous system, with different cellular and temporal profiles. Through its ability to target most cells of the nervous system and its induction of pleiotropic effects, LPA mediates events during neural development and adulthood. In this review, we summarize the current knowledge on the effects of LPA in the nervous system, during development and adulthood, and in various pathologies of the nervous system. We also explore potential LPA intervention strategies for anti-LPA therapeutics.

  10. Error-prone replication bypass of the primary aflatoxin B1 DNA adduct, AFB1-N7-Gua.

    Science.gov (United States)

    Lin, Ying-Chih; Li, Liang; Makarova, Alena V; Burgers, Peter M; Stone, Michael P; Lloyd, R Stephen

    2014-06-27

    Hepatocellular carcinomas (HCCs) are the third leading cause of cancer deaths worldwide. The highest rates of early onset HCCs occur in geographical regions with high aflatoxin B1 (AFB1) exposure, concomitant with hepatitis B infection. Although the carcinogenic basis of AFB1 has been ascribed to its mutagenic effects, the mutagenic property of the primary AFB1-DNA adduct, AFB1-N7-Gua, in mammalian cells has not been studied extensively. Taking advantage of the ability to create vectors containing a site-specific DNA adduct, the mutagenic potential was determined in primate cells. This adduct was highly mutagenic following replication in COS-7 cells, with a mutation frequency of 45%. The spectrum of mutations was predominantly G to T base substitutions, a result that is consistent with previous mutation data derived from aflatoxin-associated HCCs. To assess which DNA polymerases (pol) might contribute to the mutational outcome, in vitro replication studies were performed. Unexpectedly, replicative pol δ and the error-prone translesion synthesis pol ζ were able to accurately bypass AFB1-N7-Gua. In contrast, replication bypass using pol κ was shown to occur with low fidelity and could account for the commonly detected G to T transversions.

  11. Electrical and Biological Effects of Transmission Lines: A Review.

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jack M.

    1989-06-01

    This review describes the electrical properties of a-c and d-c transmission lines and the resulting effects on plants, animals, and people. Methods used by BPA to mitigate undesirable effects are also discussed. Although much of the information in this review pertains to high-voltage transmission lines, information on distribution lines and electrical appliances is included. The electrical properties discussed are electric and magnetic fields and corona: first for alternating-current (a-c) lines, then for direct current (d-c).

  12. Some features of irradiated chitosan and its biological effect

    Energy Technology Data Exchange (ETDEWEB)

    Hai, Le; Hien, Nguyen Quoc; Luan, Le Quang; Hanh, Truong Thi; Man, Nguyen Tan; Ha, Pham Thi Le; Thuy, Tran Thi [Nuclear Research Institute, VAEC, Dalat (Viet Nam); Yoshii, Fumio; Kume, Tamikazu [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    2001-03-01

    Preparation of chitosan oligomer by radiation degradation was carried out on the gamma Co-60 source. The radiation degradation yield (G{sub d}) of the chitosan was found to be of 1.03. The oligochitosan with 50% of dp>8 fraction was obtained by irradiating the 10% (w/v) chitosan solution in 5% acetic acid at 45 kGy for the chitosan having the initial viscometric average molecular weight, Mv=60,000. Irradiated chitosan showed higher antifungal effect than that of unirradiated one. Furthermore, the irradiated chitosan also showed the growth-promotion effect for plants. (author)

  13. 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...

  14. Nanoscaled biological gated field effect transistors for cytogenetic analysis

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Dimaki, Maria; Andersen, Karsten Brandt;

    2014-01-01

    Cytogenetic analysis is the study of chromosome structure and function, and is often used in cancer diagnosis, as many chromosome abnormalities are linked to the onset of cancer. A novel label free detection method for chromosomal translocation analysis using nanoscaled field effect transistors...

  15. Biological effects of ionizing radiations; Effets biologiques des rayonnements ionisants

    Energy Technology Data Exchange (ETDEWEB)

    Nenot, J.C. [CEA Fontenay-aux-Roses, 92 (France). Inst. de Protection et de Surete Nucleaire]|[Commission Internationale de protection radiologique (France)]|[Association Internationale de Radiopathologie (France)

    1999-01-01

    Since ten years the ionizing radiations are more and more often used in various domains as medical, industrial or research sector. In the same way, these radiation impacts on the environment and the living organisms, have been studied intensively. The effects mechanism knowledge improved considerably and allowed to better protect the workers and the public. (A.L.B.)

  16. Biological Effects of Electromagnetic Fields on Cellular Growth

    Science.gov (United States)

    Eftekhari, Beheshte; Wilson, James; Masood, Samina

    2012-10-01

    The interaction of organisms with environmental magnetic fields at the cellular level is well documented, yet not fully understood. We review the existing experimental results to understand the physics behind the effects of ambient magnetic fields on the growth, metabolism, and proliferation of in vitro cell cultures. Emphasis is placed on identifying the underlying physical principles responsible for alterations to cell structure and behavior.

  17. Resource Letter BELFEF-1: Biological effects of low-frequency electromagnetic fields

    Science.gov (United States)

    Hafemeister, David

    1996-08-01

    This Resource Letter provides a guide to the literature on the interaction of extremely low-frequency electromagnetic field (ELF/EMF) interactions with biological matter, and on the possibility that such interactions could have a harmful effect on human health. Journal articles and books are cited for the following topics: ELF/EMF theoretical interactions with biological cells, organs and organisms, magnetic dipole interactions, sensing by animals, biomedical-biophysical experiments, epidemiology, and litigation-mitigation risk issues.

  18. Stability, accumulation and cytotoxicity of an albumin-cisplatin adduct

    DEFF Research Database (Denmark)

    Møller, Charlotte; Tastesen, Hanne Sørup; Gammelgaard, Bente

    2010-01-01

    The accumulation and cytotoxicity of a 10 µmol L¿¹ equimolar human serum albumin-cisplatin adduct (HSA-Pt) was investigated in suspension Ehrlich Ascites Tumor Cells (EATC) and adherent Ehrlich Lettré Ascites Cells (Lettré). HSA-Pt did not induce apoptosis nor was it taken up by the cells to any...... significant amount within 24 h incubation. The accumulation and cytotoxicity of HSA-Pt was compared to 10 µmol L¿¹ cisplatin for which a larger accumulation and cytotoxicity were observed in EATC compared to Lettré. The experiment was performed with cell medium exchange every fourth hour as HSA...

  19. Biological activities and health effects of terpenoids from marine fungi.

    Science.gov (United States)

    Kim, Se-Kwon; Li, Yong-Xin

    2012-01-01

    Recently, a great deal of interest has been developed by the consumers toward natural bioactive compounds as functional ingredients in the nutraceutical, cosmeceutical, and pharmaceutical products due to their various health beneficial effects. Hence, it can be suggested that bioactive functional ingredients from marine bioresources and their by-products are alternative sources for synthetic ingredients that can contribute to consumer's well-being, as a part of nutraceuticals and functional foods. Marine-derived fungi produce a vast array of secondary metabolites including terpenes, steroids, polyketides, peptides, alkaloids, and polysaccharides. These secondary metabolites serve many biopharmaceutical purposes. This chapter discusses about marine fungi-derived terpenoids and presents an overview of their beneficial health effects.

  20. Biological Effects of Nonionizing Electromagnetic Radiation. Volume IV. Number 3.

    Science.gov (United States)

    1980-03-01

    teratogenesis in mealworms (9-10 GHz at total power CENTRAL NERVOUS SYSTEM, BEHAVIOR, AND of 20-80 mW) and in mice (2,450 MHz, energy absorp- BLOOD: A PROGRESS...behavioral changes, diseases are discussed and three case reports dem- malaise, restlessness, sterilization, fetal damage, onstrating this problem are...April, 1979. exposure of Moscow Embassy employees in the causa - (7 refs) tion of any adverse health effects. Four studies to determine the health

  1. Biologic Effects of Dopamine on Tumor Vasculature in Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Myrthala Moreno-Smith

    2013-05-01

    Full Text Available Chronic sympathetic nervous system activation results in increased angiogenesis and tumor growth in orthotopic mouse models of ovarian carcinoma. However, the mechanistic effects of such activation on the tumor vasculature are not well understood. Dopamine (DA, an inhibitory catecholamine, regulates the functions of normal and abnormal blood vessels. Here, we examined whether DA, an inhibitory catecholamine, could block the effects of chronic stress on tumor vasculature and tumor growth. Exogenous administration of DA not only decreased tumor microvessel density but also increased pericyte coverage of tumor vessels following daily restraint stress in mice. Daily restraint stress resulted in significantly increased tumor growth in the SKOV3ip1 and HeyA8 ovarian cancer models. DA treatment blocked stress-mediated increases in tumor growth and increased pericyte coverage of tumor endothelial cells. Whereas the antiangiogenic effect of DA is mediated by dopamine receptor 2 (DR2, our data indicate that DA, through DR1, stimulates vessel stabilization by increasing pericyte recruitment to tumor endothelial cells. DA significantly stimulated migration of mouse 10T1/2 pericyte-like cells in vitro and increased cyclic adenosine mono-phosphate (cAMP levels in these cells. Moreover, DA or the DR1 agonist SKF 82958 increased platinum concentration in SKOV3ip1 tumor xenografts following cisplatin administration. In conclusion, DA stabilizes tumor blood vessels through activation of pericyte cAMP-protein kinase A signaling pathway by DR1. These findings could have implications for blocking the stimulatory effects of chronic stress on tumor growth.

  2. BIOLOGICAL EFFECTS OF TNF-BINDING VARIOLAVIRUS RECOMBINANT PROTEIN

    Directory of Open Access Journals (Sweden)

    I. A. Orlovskaya

    2012-01-01

    Full Text Available Abstract. This review presents a summary of our data concerning in vivo and in vitro effects of recombinant TNF-binding protein from variola virus (VARVCrmB upon TNF-induced functional changes of human and murine cells. VARV-CrmB protein blocks TNF-induced production of IL-1β and IL-6 by human mononuclear cells, and their in vitro oxidation-related metabolic (OM activity. VARV-CrmB protein restores TNF-induced reduction of BFU-E+CFU-E colony-forming activity and normalizes TNF-induced effects upon CFU-GM formation in a colony-forming model of human and murine bone morrow cells (BMC. VARV-CrmB protein displays a pronounced in vivo alleviation of LPS-induced endotoxic shock symptoms in SPF BALB/C mice thus significantly increasing survival of experimental animals. Moreover, VARV-CrmBprotein decreases intensity of collagen-induced arthritis at early terms. Application of VARV-CrmB protein results in normalization of TNF-induced increase of migratory and OM activity of murine leukocytes, and exerts corrective effects upon colony-forming ability of murine hematopoietic precursors. Skin application of VARV-CrmB protein decreases leukocyte migration from a skin scrap in afferent phase of DNCB-induced contact reaction, as well as “ear oedema” index. Our results demonstrate TNF-blocking properties of VARVCrmB protein. In summary, our data allow to consider a recombinant variola virus VARV-CrmB as a new potential TNF-antagonist. Its effects can be explained by its ability of neutralizing TNF-induced activation of oxidation-related metabolic, cytokine-producing and migratory functions of effector cells in therapy of pathological inflammatory processes.

  3. Radioactivity in the ocean: laws and biological effects

    Energy Technology Data Exchange (ETDEWEB)

    Hunsaker, C.T.

    1985-01-01

    This paper summarizes the literature on US laws and international agreements, experimental and monitoring data, and ongoing studies to provide background information for environmental assessment and regulatory compliance activities for ocean dumping of low-level radioactive waste. The Marine Protection, Research, and Sanctuaries Act is the major US legislation governing ocean disposal of radioactive waste. The major international agreement on ocean dumping is the Convention on the Prevention of Marine Pollution by Dumping of Wastes and other Matter. The United States ended its ocean dumping of radioactive wastes in 1970, but other countries have continued ocean dumping under international supervision in the northeast Atlantic. Monitoring of former US disposal sites has neither revealed significant effects on marine biota nor indicated a hazard to human health. Also, no effects on marine organisms have been found that could be attributed to routine discharges into the Irish Sea from the Windscale reprocessing plant. We must improve our ability to predict the oceanic carrying capacity and the fate and effects of ionizing radiation in the marine environment.

  4. Biological Effects of Culture Substrates on Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Yohei Hayashi

    2016-01-01

    Full Text Available In recent years, as human pluripotent stem cells (hPSCs have been commonly cultured in feeder-free conditions, a number of cell culture substrates have been applied or developed. However, the functional roles of these substrates in maintaining hPSC self-renewal remain unclear. Here in this review, we summarize the types of these substrates and their effect on maintaining hPSC self-renewal. Endogenous extracellular matrix (ECM protein expression has been shown to be crucial in maintaining hPSC self-renewal. These ECM molecules interact with integrin cell-surface receptors and transmit their cellular signaling. We discuss the possible effect of integrin-mediated signaling pathways on maintaining hPSC self-renewal. Activation of integrin-linked kinase (ILK, which transmits ECM-integrin signaling to AKT (also known as protein kinase B, has been shown to be critical in maintaining hPSC self-renewal. Also, since naïve pluripotency has been widely recognized as an alternative pluripotent state of hPSCs, we discuss the possible effects of culture substrates and integrin signaling on naïve hPSCs based on the studies of mouse embryonic stem cells. Understanding the role of culture substrates in hPSC self-renewal and differentiation enables us to control hPSC behavior precisely and to establish scalable or microfabricated culture technologies for regenerative medicine and drug development.

  5. [Effects and Biological Response on Bioremediation of Petroleum Contaminated Soil].

    Science.gov (United States)

    Yang, Qian; Wu, Man-li; Nie, Mai-qian; Wang, Ting-ting; Zhang, Ming-hui

    2015-05-01

    Bioaugmentation and biostimulation were used to remediate petroleum-contaminated soil which were collected from Zichang city in North of Shaanxi. The optimal bioremediation method was obtained by determining the total petroleum hydrocarbon(TPH) using the infrared spectroscopy. During the bioremediation, number of degrading strains, TPH catabolic genes, and soil microbial community diversity were determined by Most Probable Number (MPN), polymerase chain reaction (PCR) combined agarose electrophoresis, and PCR-denaturing gradient electrophoresis (DGGE). The results in different treatments showed different biodegradation effects towards total petroleum hydrocarbon (TPH). Biostimulation by adding N and P to soils achieved the best degradation effects towards TPH, and the bioaugmentation was achieved by inoculating strain SZ-1 to soils. Further analysis indicated the positive correlation between catabolic genes and TPH removal efficiency. During the bioremediation, the number of TPH and alkanes degrading strains was higher than the number of aromatic degrading strains. The results of PCR-DGGE showed microbial inoculums could enhance microbial community functional diversity. These results contribute to understand the ecologically microbial effects during the bioremediation of petroleum-polluted soil.

  6. Structural perturbations induced by the alpha-anomer of the aflatoxin B(1) formamidopyrimidine adduct in duplex and single-strand DNA.

    Science.gov (United States)

    Brown, Kyle L; Voehler, Markus W; Magee, Shane M; Harris, Constance M; Harris, Thomas M; Stone, Michael P

    2009-11-11

    and base levels. The structural distortions and the less favorable stacking interactions induced by the AFB-alpha-FAPY adduct explain its lower stability as compared to the AFB-beta-FAPY adduct in duplex DNA. In this DNA sequence, hydrogen bonding between the formyl oxygen and the exocyclic amine of the 3'-neighboring adenine stabilizing the E configuration of the formamide moiety is also observed for the AFB-beta-FAPY adduct, and suggests that the identity of the 3'-neighbor nucleotide modulates the stability and biological processing of AFB adducts.

  7. Aromatic DNA adducts in human white blood cells and skin after dermal application of coal tar

    Energy Technology Data Exchange (ETDEWEB)

    Godschalk, R.W.L.; Ostertag, J.U.; Moonen, E.J.C.; Neumann, H.A.M.; Kleinjans, J.C.S.; Schooten, F.J. van [University of Maastricht, Maastricht (Netherlands). Dept. of Health Risk Analysis and Toxicology

    1998-09-01

    A group of eczema patients topically treated with coal tar (CT) ointments was used as a model population to examine the applicability of DNA adducts in white blood cell (WBC) subpopulations as a measure of dermal exposure to polycyclic aromatic hydrocarbons (PAHs). Aromatic DNA adducts were examined by {sup 32}P-postlabeling in exposed skin and WBC subsets, and urinary excretion of PAH metabolites was determined to assess the whole-body burden. The median urinary excretion of 1-hydroxypyrene and 3-hydroxybenzo(a)pyrene was 0.39 and 0.01 {mu}mol/mol creatinine respectively, before the dermal application of CT ointments. After treatment for 1 week, these levels increased to 139.7 and 1.18 {mu}mol/mol creatinine respectively, indicating that considerable amounts of PAHs were absorbed. Median aromatic DNA adduct levels were significantly increased in skin from 2.9 adduct/10{sup 8} nucleotides before treatment to 63.3 adducts/10{sup 8} nt after treatment with CT, in monocytes from 0.28 to 0.86 adducts/10{sup 8} nt, in lymphocytes from 0.33 to 0.89 adducts/10{sup 8} nt and in granulocytes from 0.28 to 0.54 adducts/10{sup 8} nt. A week after stopping the CT treatment, the DNA adduct levels in monocytes and granulocytes were reduced to 0.38 and 0.38 adducts/10{sup 8} nt respectively, whereas the adduct levels in lymphocytes remained enhanced. Total DNA adduct levels in skin correlated with the adduct levels in monocytes and lymphocytes. Excretion of urinary metabolites during the first week of treatment was correlated with the percentage of the skin surface treated with CT ointment and decreased within a week after the cessation of treatment. 3-Hydroxybenzo(a)pyrene excretion, correlated with the levels of DNA adducts in skin that comigrated with benzo(a)pyrene-diol-epoxide-DNA. This study indicates that the DNA adduct levels in mononuclear WBCs can possibly be used as a surrogate for skin DNA after dermal exposure to PAHs. 34 refs., 4 figs., 1 tab.

  8. Differences in lysine adduction by acrolein and methyl vinyl ketone: implications for cytotoxicity in cultured hepatocytes.

    Science.gov (United States)

    Kaminskas, Lisa M; Pyke, Simon M; Burcham, Philip C

    2005-11-01

    Acrolein is a highly toxic environmental pollutant that readily alkylates the epsilon-amino group of lysine residues in proteins. In model systems, such chemistry involves sequential addition of two acrolein molecules to a given nitrogen, forming bis-Michael-adducted species that undergo aldol condensation and dehydration to form Nepsilon-(3-formyl-3,4-dehydropiperidino)lysine. Whether this ability to form cyclic adducts participates in the toxicity of acrolein is unknown. To address this issue, we compared the chemistry of protein adduction by acrolein to that of its close structural analogue methyl vinyl ketone, expecting that the alpha-methyl group would hinder the intramolecular cyclization of any bis-adducted species formed by methyl vinyl ketone. Both acrolein and methyl vinyl ketone displayed comparable protein carbonylating activity during in vitro studies with the model protein bovine serum albumin, confirming the alpha,beta,-unsaturated bond of both compounds is an efficient Michael acceptor for protein nucleophiles. However, differences in adduction chemistry became apparent during the use of electrospray ionization-MS to monitor reaction products in a lysine-containing peptide after modification by each compound. For example, although a Schiff base adduct was detected following reaction of the peptide with acrolein, an analogous species was not formed by methyl vinyl ketone. Furthermore, while ions corresponding to mono- and bis-Michael adducts were detected at the N-terminus and lysine residues following peptide modification by both carbonyls, only acrolein modification generated ions attributable to cyclic adducts. Despite these differences in adduction chemistry, in mouse hepatocytes, the two compounds exhibited very comparable abilities to induce rapid, concentration-dependent cell death as well as protein carbonylation. These findings suggest that the acute toxicity of short-chain alpha,beta-unsaturated carbonyl compounds involves their ability to

  9. Detection of Riddelliine-Derived DNA Adducts in Blood of Rats Fed Riddelliine

    Directory of Open Access Journals (Sweden)

    Ming W. Chou

    2002-09-01

    Full Text Available Abstract: We have previously shown that riddelliine, a naturally occurring genotoxic pyrrolizidine alkaloid, induces liver tumors in rats and mice through a genotoxic mechanism mediated by the formation of a set of eight 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5Hpyrrolizine ( DHP-derived DNA adducts. In this study we report the formation of these DHP-derived DNA adducts in blood DNA of rats fed riddelliine. In an adduct formation and removal experiment, male and female F344 rats (8 weeks of age were administered riddelliine by gavage at a single dose of 10.0 mg/kg body weight in 0.1 M phosphate buffer. At 8, 24, 48, and 168 hrs after dosing, the levels of DHP-derived DNA adduct in blood and liver were determined by 32P-postlabeling/HPLC. Maximum DNA adduct formation occurred at 48 hr after treatment. From 48 to 168 hours, the adduct levels in female rat blood were 4-fold greater than those in male rats. In a dose response experiment, female rats were gavaged 0.1 and 1.0 mg/kg doses of riddelliine for three consecutive days and the DHPderived DNA adducts in blood DNA were assayed. The levels of the DHP-derived DNA adducts in blood of rats receiving 0.1 and 1.0 mg/kg doses were 12.9 and 51.8 adducts/107 nucleotides. These results suggest that: (i leucocyte DNA can bind with DHP to form a set of DHP-derived DNA adducts generated in liver; (ii DHP-derived DNA adducts in blood can serve as a potential non-invasive biomarkers for assessing the exposure to riddelliine.

  10. Effect of biologic therapy on radiological progression in rheumatoid arthritis: what does it add to methotrexate?

    Directory of Open Access Journals (Sweden)

    Jones G

    2012-07-01

    Full Text Available Graeme Jones, Erica Darian-Smith, Michael Kwok, Tania WinzenbergMenzies Research Institute, University of Tasmania, Tasmania, AustraliaAbstract: There have been substantial advances in the treatment of rheumatoid arthritis in recent years. Traditional disease-modifying antirheumatic drugs (DMARDs have been shown to have small effects on the progression of radiographic damage. This quantitative overview summarizes the evidence for biologic DMARDS and radiographic damage either alone or in combination with methotrexate. Two outcomes were used (standardized mean difference and odds of progression. A total of 21 trials were identified of which 18 had useable data. For biologic monotherapy, tocilizumab, adalimumab, and etanercept were significantly better than methotrexate, with tocilizumab ranking first in both outcomes while golimumab was ineffective in both outcomes. For a biologic in combination with methotrexate compared with methotrexate alone, most therapies studied (etanercept, adalimumab, infliximab, certolizumab, tocilizumab, and rituximab were effective at slowing X-ray progression using either outcome, with infliximab ranking first in both outcomes. The exceptions to this were golimumab (no effect on standardized mean difference and abatacept (no effect on odds of progression. This effect was additional to methotrexate; thus, the overall benefit is moderate to large in magnitude, which is clearly of major clinical significance for sufferers of rheumatoid arthritis and supports the use of biologic DMARDs in those with a poor disease prognosis.Keywords: rheumatoid, trials, meta-analysis, radiographs, biologic, disease-modifying antirheumatic drugs, DMARDs

  11. EFFECTS OF 5E LEARNING CYCLE ON STUDENTS ACHIEVEMENT IN BIOLOGY AND CHEMISTRY

    Directory of Open Access Journals (Sweden)

    Patrick Osawaru Ajaja,

    2012-01-01

    Full Text Available The major purpose of this study was to determine the effects of learning cycle as an instructional strategy on biology andchemistry students achievement. To guide this study, six research hypotheses were stated and tested at 0.05 level ofsignificance. The design of this study was 2x2x3x6 Pre-test Post-test non-equivalent control group quasi experimental design.These included two instructional groups (experimental and control groups, sex (male and female, repeated testing (Pre,Post and follow-up tests, and six weeks of experience. The samples of the study included six senior secondary schools, 112science students, and 12 biology and chemistry teachers. The instruments used for this study were: teacher’s questionnaireon knowledge and use of learning cycle (KULC; and Biology and Chemistry Achievement Test (BCAT. The data collected wereanalyzed with simple percentage, Analysis of Covariance (ANCOVA and student t-test statistics. The major findings of thestudy included that only 30.43% and 26.31% of biology and chemistry teachers have the knowledge that learning cycle is aninstructional method; all the biology and chemistry teachers sampled have never used learning cycle as an instructionalmethod; learning cycle had a significant effect on students achievement in biology and chemistry; students taught withlearning cycle significantly achieved better in biology/chemistry Post-test than those taught with lecture method; the posttestscores of students in the learning cycle group increased over the period of experience; non-significant difference in Posttestscores between males and females taught with learning cycle; non-significant interaction effect between method andsex on achievement; and a significant higher retention of biology and chemistry knowledge by students taught with learningcycle than those taught with lecture method. It was concluded that the method seems an appropriate instructional modelthat could be used to solve the problems of

  12. Biological effect of non-ionizing radiations on microorganisms

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, Kikuo; Yamamoto, Takayoshi [Osaka Univ., Radioisotope Research Center, Suita, Osaka (Japan); Nakaoka, Yasuo [Osaka Univ., Graduate School of Engineering Science, Department of Biophysical Engineering, Toyonaka, Osaka (Japan)

    2000-05-01

    We studied the effect of extremely low frequency magnetic fields (ELF-MF) of 60-Hz and 500 mT on the growth and the mutation frequency of the budding yeast S.cerevisiae and on the behavior of the ciliate Paramecium multimicronucleatum. The growth rate and mutation frequencies of several strains of S.cerevisiae (wild type and radiation sensitive mutants, rad or rev) were examined but no significant difference was observed. Moreover, the behavior of P.multimicronucleatum under the ELF-MF was examined. When exposed to a vertical field of 0.6 T, the cells accumulated at the upper end of the cuvette. (author)

  13. Oil spills: Biological effects. (Latest citations from the NTIS bibliographic database). Published Search

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-06-01

    The bibliography contains citations concerning the biological and ecological effects of oil spills. Citations discuss effects on microorganisms, plants, and animals. Damage assessment, ecological modeling, and environmental impact statements are included. (Contains 50-250 citations and includes a subject term index and title list.) (Copyright NERAC, Inc. 1995)

  14. Low power laser therapy — an introduction and a review of some biological effects

    OpenAIRE

    Thiel, Haymo

    1986-01-01

    This report gives a brief introduction to the characteristics of therapeutic low power laser devices. Absorption, tissue penetration and physiological mechanisms of laser irradiation are discussed. The biological effects of low power laser light are reviewed in the areas of collagen metabolism, woundhealing, inflammation and pain control. Contraindications, precautions and side effects of low power laser irradiation are discussed.

  15. Catalytically and noncatalytically treated automobile exhaust: biological effects in rats

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, G.P. (Univ. of Cincinnati); Lewkowski, J.P.; Hastings, L.; Malanchuk, M.

    1977-12-01

    Chronic exposure to catalytically treated or noncatalytically treated automobile exhaust significantly depressed the spontaneous locomotor activity (SLA) of rats. Exposure to H/sub 2/SO/sub 4/ alone or CO at comparable levels did not alter the SLA. Exposure to noncatalytically treated exhaust resulted in significant reductions in growth rate and food and water intake. However, these effects were not evident in the exposure to catalytically treated exhaust or in the control H/sub 2/SO/sub 4/ and CO exposures. Blood acid-base analyses indicated that exposure to either catalytically treated exhaust or H/sub 2/SO/sub 4/ elicits a metabolic alkalosis, while exposure to CO alone results in a metabolic acidosis. All acid-base parameters were within the normal range several weeks after the termination of exposure.

  16. Synthesis and Isolation of cis-2 Regiospecific Ethylene-Tethered Indene Dimer-[70]Fullerene Adduct for Polymer Solar Cell Applications.

    Science.gov (United States)

    Tao, Ran; Umeyama, Tomokazu; Higashino, Tomohiro; Koganezawa, Tomoyuki; Imahori, Hiroshi

    2015-08-05

    Although the utilization of [70]fullerene bis-adducts can enhance the power conversion efficiencies of polymer solar cells (PSCs) owing to their strong absorption intensities and high-lying lowest unoccupied molecular orbital energy levels, this synthetic strategy typically yields a mixture of regioisomers that would mask the intrinsic device performances depending on the substituent pattern on the [70]fullerene derivatives. In this study, a single cis-2 regioisomer of C70 bis-adduct (cis-2-[70]BIEC) has been prepared for the first time by the same strategy that had been applied to [60]fullerene to obtain a regioisomerically pure C60 bis-adduct (cis-2-[60]BIEC). Diels-Alder reaction was conducted between a rationally designed ethylene-tethered indene dimer and [70]fullerene, followed by isolation using high-performance liquid chromatography suitable for the separation of fullerene derivatives. A series of structural analysis techniques including NMR spectroscopies and X-ray crystallography were used to identify the absolute configuration of the bis-adduct. A systematic study on the optical, electrochemical, and photovoltaic properties of cis-2-[70]BIEC as well as the corresponding regioisomer mixture (bis-[70]BIEC) and the monoadduct (α-mono-[70]BIEC) has been performed to examine the effect of the pure cis-2 regioisomer. More importantly, their properties are compared with those of cis-2-[60]BIEC to address the effect of fullerene cage structures, that is, C60 versus C70. The PSC based on cis-2-[70]BIEC and poly(3-hexylthiophene) showed a remarkable power conversion efficiency of 4.2%, which is higher than those with bis-[70]BIEC (2.2%), α-mono-[70]BIEC (2.2%), cis-2-[60]BIEC (2.8%), and even a prevalent high-performance C70 monoadduct ([70]PCBM, 3.8%). Our synthetic strategy will pave the way for further development on the rational design and isolation of single fullerene bis-adduct regioisomers exhibiting high device performances.

  17. Modeling the conformational preference of the carbon-bonded covalent adduct formed upon exposure of 2'-deoxyguanosine to ochratoxin A.

    Science.gov (United States)

    Sharma, Purshotam; Manderville, Richard A; Wetmore, Stacey D

    2013-05-20

    The conformational flexibility of the C8-linked guanine adduct formed from attachment of ochratoxin A (OTA) was analyzed using a systematic computational approach and models ranging from the nucleobase to the adducted DNA helix. A focus was placed on the influence of the C8-modification of 2'-deoxyguanosine (dG) on the preferred relative arrangement of the nucleobase and the C8-substituent and, more importantly, the anti/syn conformational preference with respect to the glycosidic bond. Although OTA is twisted with respect to the base in the nucleobase model, addition of the deoxyribose sugar induces a further twist and restricts rotation about the C-C linkage due to close contacts between OTA and the sugar. The nucleoside model preferentially adpots a syn orientation (by 10-20 kJ mol(-1) depending on the OTA conformation) due to the presence of an O5'-H···N3 interaction. However, when this hydrogen bond is eliminated, which better mimics the DNA environment, a small (simulations and free energy analysis predict that both syn- and anti-conformations of OTB-dG are equally stable in helices when paired opposite cytosine. These results indicate that the adduct will likely adopt a syn conformation in an isolated nucleoside and nucleotide, while a mixture of syn and anti conformations will be observed in DNA duplexes. Since the syn conformation could stabilize base mismatches upon DNA replication or Z-DNA structures with varied biological outcomes, future computational and experimental work should elucidate the consequences of the conformational preference of this potentially harmful DNA lesion.

  18. [Quality of interior air: biological contaminants and their effects on health; bioaerosols and gathering techniques].

    Science.gov (United States)

    Bălan, Gabriela

    2007-01-01

    Indoor Air Quality: biological contaminants and health effects; airborne organisms and sampling instruments. Biological contaminants include bacteria, molds, viruses, animal dander and cat saliva, house dust, mites, cockroaches and pollen. Symptoms of health problems caused by biological pollutants include sneezing, watery eyes, coughing, shortness of breath, dizziness, lethargy, fevers. Children, elderly people with breathing problems, allergies and lung diseases are particularly susceptible to disease-causing biological agents in the indoor air. It is convenient to consider microbiological samplers for collecting organisms in air as falling into several broad categories. Many popular microbiological air samplers use the principle of impaction to trap the organisms by impacting them directly on to agar. Further distinct groups are the impingers, which operate by impinging organisms into liquid.

  19. [Adipogenic function and other biologic effects of insulin].

    Science.gov (United States)

    Pankov, Y A

    2016-01-01

    Studies on experimental animals with knockout of the insulin receptor gene Insr (in the whole body or in certain tissues) and/or related genes encoding proteins involved in realization of insulin signal transduction in target cells, have made an important contribution to the elucidation of insulin regulation of metabolism, particularly fat metabolism. Since the whole insulin secreted by b-cells, together with the products of gastrointestinal tract digestion of proteins, fats, and carbohydrates reach the liver, the latter is the first organ on which this hormone acts. The liver employs released amino acids for synthesis of proteins, including apoproteins for various lipoproteins. Glucose is used for synthesis of glycogen, fatty acids, and triglycerides, which enter all the organs in very low density lipoproteins (VLDL). The LIRKO mice with knockout of the Insr gene in the liver demonstrated inhibition of synthesis of macromolecular compounds from amino acids, glucose, and fatty acids. Low molecular weight substances demonstrated increased entry to circulation, and together with other disorders induced hyperglycemia. In LIRKO mice blood glucose levels and glucose tolerance demonstrated time-dependent normalization and at later stages the increase in glucose levels was replaced by hypoglycemia. These changes can be well explained if we take into consideration that one of the main functions of insulin consists in stimulation of energy accumulation by means of activation of triglyceride deposition in adipose tissue. FIRKO mice with selective knockout of adipose tissue Insr were characterized by decreased uptake of glucose in adipocytes, and its transformation into lipids. However, the level of body fat in animals remained normal, possibly due to preserved insulin receptor in the liver and insulin-induced activation of triglyceride production which maintained normal levels of body fat stores, the effective functioning of adipose tissue and secretion of leptin by

  20. Biologic effects of fenbendazole in rats and mice: a review.

    Science.gov (United States)

    Villar, David; Cray, Carolyn; Zaias, Julia; Altman, Norman H

    2007-11-01

    This review summarizes findings from toxicologic, carcinogenic, immunologic, and metabolic studies on fenbendazole (FBZ). Currently, FBZ is used to treat or prevent pinworm outbreaks in laboratory rodents. Because antiparasitic treatments usually are not part of experimental designs, interactions from the medication on the outcomes of ongoing experiments are a concern. At therapeutic levels, FBZ does not alter the total content of cytochromes P450 but does induce certain hepatic cytochrome P450 isoforms, namely 1A1, 1A2, and 2B1. Although expressed constitutively at low or undetectable levels, these isoforms particularly are known for bioactivating a number of procarcinogens. Lifetime studies in rats have shown that FBZ is not a carcinogen but that it may behave as a tumor promoter when given after certain initiators. Unlike in other animal species, FBZ treatment-associated myelosuppression has not been reported to occur in rodents. The few currently available immunologic studies in mice, including an autoimmune model, have not shown effects on selected immune responses. However, data from other animal species suggest that the ability of B and T lymphocytes to proliferate in the secondary immune response may be suppressed during treatment with FBZ.

  1. Cardiometabolic risk in psoriasis: differential effects of biologic agents

    Directory of Open Access Journals (Sweden)

    Mariana J Kaplan

    2008-12-01

    Full Text Available Mariana J KaplanDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USAAbstract: Psoriasis is associated to an increased risk of cardiovascular (CV complications. Overall, the pathogenic mechanisms involved in premature CV complications in psoriasis appear to be complex and multifactorial, with traditional and nontraditional risk factors possibly contributing to the increased risk. Based on what is known about the pathogenesis of psoriasis and extrapolating the current knowledge on CV complications in other inflammatory diseases, studies are needed to investigate if appropriate control of the inflammatory, immunologic and metabolic disturbances present in psoriasis can prevent the development of this potentially lethal complication. It is clear that there is a great need for heightened awareness of the increased risk for vascular damage in patients with psoriasis. It is also crucial to closely monitor patients with psoriasis for CV risk factors including obesity, hypertension, diabetes, and hyperlipidemia. Whether treatment regimens that effectively manage systemic inflammation will lead to prevention of CV complications in psoriasis needs to be investigated. Clearly, studies should focus on establishing the exact mechanisms that determine CV risk in psoriasis so that appropriate preventive strategies and treatment guidelines can be established.Keywords: psoriasis, atherosclerosis, inflammation, vascular

  2. The biological effect and medical functions of the Infrared Rays

    Institute of Scientific and Technical Information of China (English)

    PANG Xiao-feng

    2001-01-01

    The quantum vibrational energy-spectra including high excited states of the protein molecules have been calculated by new theory of bio-energy transport along the protein molecules and its dynamic equation, discrete nonlinear Schrodinger equation, appropriate to the protein molecules on the basis of the level of molecular structure. This energy-spectra obtained are basically consistent with the experimental values by infrared absorption and radiated measurement of person's hands and laser-Raman spectrum from metabolically active E. Coli.. From this energy-spectra we know that the infrared lights with (1-3)x1000nm and (5-7)x1000nm wavelength can be absorbed by the protein molecules in the living systems.In accordance with the non-linear theory of the bio-energy transport we know that the energy of the infrared light absorbed by the proteins can result in vibrations of amide-I in amino acids and can facilitate the bio-energy transport along the protein molecular chains from one place to other for the growth of living bodies. This processe is non-thermal. This is just non-thermal effect of the infrared lights. According to the mechanism we explained further the medical functions of the infrared lights absorbed.

  3. Biological effects of exposure to intermediate neutron and repair mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Utsumi, Hiroshi; Sasaki, Masao [Kyoto Univ. (Japan); Onishi, Takeo; Onizuka, Masahiko

    2000-01-01

    An investigation was made on cytotoxic effects of neutron capture using chicken B-cell line mutants, DT40, KURO{sup -/-}, RAD54 {sup -/-} and KU70{sup -/-} / RAD54{sup -/-}. Suspensions of these cells were exposed to two times X-radiation at various doses and the cell surviving was evaluated. The sensitivity to radiation was highest in the double defective mutant, KU70{sup -/-} / RAD54{sup -/-} and followed by that of RAD54 {sup -/-}, a homologous recombination mutant, whereas KURO {sup -/-} cell, a non-homologous end-joining mutant showed a peculiar surviving curve composed of two phases and the cell was highly sensitive to a low-dose radiation. This indicates that there are two different DNA repair systems for double-strand breaks and the system for non-homologous end-joining repair can be involved in all phases of cell cycle, but the system for the homologous one is involved only in S-phase. Therefore, it was thought that variation of sensitivity to radiation exposure depending to the phase of cell cycle might explain the alternation of repair system depending to the phase progressing of cell cycle. It was thus likely that the recovery from radiation injury, which is still a black box might be explained with the double strand breaks of DNA. (M.N.)

  4. Bioaccumulation and biological effects of cigarette litter in marine worms

    Science.gov (United States)

    Wright, Stephanie L.; Rowe, Darren; Reid, Malcolm J.; Thomas, Kevin V.; Galloway, Tamara S.

    2015-01-01

    Marine debris is a global environmental issue. Smoked cigarette filters are the predominant coastal litter item; 4.5 trillion are littered annually, presenting a source of bioplastic microfibres (cellulose acetate) and harmful toxicants to marine environments. Despite the human health risks associated with smoking, little is known of the hazards cigarette filters present to marine life. Here we studied the impacts of smoked cigarette filter toxicants and microfibres on the polychaete worm Hediste diversicolor (ragworm), a widespread inhabitant of coastal sediments. Ragworms exposed to smoked cigarette filter toxicants in seawater at concentrations 60 fold lower than those reported for urban run-off exhibited significantly longer burrowing times, >30% weight loss, and >2-fold increase in DNA damage compared to ragworms maintained in control conditions. In contrast, ragworms exposed to smoked cigarette filter microfibres in marine sediment showed no significant effects. Bioconcentration factors for nicotine were 500 fold higher from seawater than from sediment. Our results illustrate the vulnerability of organisms in the water column to smoking debris and associated toxicants, and highlight the risks posed by smoked cigarette filter debris to aquatic life. PMID:26369692

  5. Fullerene–Carbene Lewis Acid–Base Adducts

    KAUST Repository

    Li, Huaping

    2011-08-17

    The reaction between a bulky N-heterocylic carbene (NHC) and C60 leads to the formation of a thermally stable zwitterionic Lewis acid-base adduct that is connected via a C-C single bond. Low-energy absorption bands with weak oscillator strengths similar to those of n-doped fullerenes were observed for the product, consistent with a net transfer of electron density to the C60 core. Corroborating information was obtained using UV photoelectron spectroscopy, which revealed that the adduct has an ionization potential ∼1.5 eV lower than that of C60. Density functional theory calculations showed that the C-C bond is polarized, with a total charge of +0.84e located on the NHC framework and -0.84e delocalized on the C 60 cage. The combination of reactivity, characterization, and theoretical studies demonstrates that fullerenes can behave as Lewis acids that react with C-based Lewis bases and that the overall process describes n-doping via C-C bond formation. © 2011 American Chemical Society.

  6. Exposure-route-dependent DNA adduct formation by polycyclic aromatic hydrocarbons

    NARCIS (Netherlands)

    Godschalk, R.W.L.; Moonen, E.J.C.; Schilderman, A.E.L.; Broekmans, W.M.R.; Kleinjans, J.C.S.; Schooten, F.J. van

    2000-01-01

    Understanding the kinetics of aromatic-DNA adducts in target tissues and white blood cells (WBC) would enhance the applicability of DNA adducts in WBC as surrogate source of DNA in biomonitoring studies. In the present study, rats were acutely exposed to benzo[a]pyrene (B[a]P; 10 mg/kg body wt) via

  7. Specific plant DNA adducts as molecular biomarkers of genotoxic atmospheric environments.

    Science.gov (United States)

    Weber-Lotfi, F; Obrecht-Pflumio, S; Guillemaut, P; Kleinpeter, J; Dietrich, A

    2005-03-01

    The general purpose of this study was to determine whether the formation of DNA addition products ('adducts') in plants could be a valuable biomarker of genotoxic air pollution. Plants from several species were exposed to ambient atmosphere at urban and suburban sites representative of different environmental conditions. The levels of NO2 and of the quantitatively major genotoxic air pollutants benzene, toluene, and xylene were monitored in parallel with plant exposure. DNA adducts were measured in bean (Phaseolus vulgaris), rye-grass (Lolium perenne), and tobacco (Nicotiana tabacum) seedlings by means of the [32P]-postlabeling method. Whereas, no correlation was found between the levels of the major genotoxic air pollutants and the total amounts of DNA adducts, individual analyses revealed site-specific and plant species-specific adduct responses, both at the qualitative and quantitative level. Among these, the amount of a specific rye-grass DNA adduct (rgs1) correlated with benzene/toluene/xylene levels above a threshold. For further characterization, rye-grass seedlings were treated in controlled conditions with benzene, toluene, xylene or their derivatives. On the other hand, in vitro DNA adduct formation assays were developed involving benzene, toluene, xylene, or their derivatives, and plant microsomes or purified peroxidase. Although in some cases, these approaches produced specific adduct responses, they failed to generate the rgs1 DNA adduct, which appeared to be characteristic for on-site test-plant exposure. Our studies have thus identified an interesting candidate for further analysis of environmental biomarkers of genotoxicity.

  8. 40 CFR 721.3680 - Ethylene oxide adduct of fatty acid ester with pentaerythritol.

    Science.gov (United States)

    2010-07-01

    ... ester with pentaerythritol. 721.3680 Section 721.3680 Protection of Environment ENVIRONMENTAL PROTECTION... New Uses for Specific Chemical Substances § 721.3680 Ethylene oxide adduct of fatty acid ester with... identified generically as ethylene oxide adduct of fatty acid ester with pentaerythritol (PMN P-91-442)...

  9. Effects of Magnetic Field on Biological Cells and Applications

    Science.gov (United States)

    Chen, Ching-Jen

    2001-03-01

    While there has been extensive research performed in the physics of magnetic fields and the physics and chemistry in life sciences, independent of each other, there has been a paucity of scientific research and development investigating the possible applications of magnetic fields in life sciences. The focus of this presentation is to present the stimulation mechanism by which magnetic fields affect (a) yeast cells (b) plant cells and (c) mammalian normal and cancer cells. Recently we have found that the Saccharomyces Cerevsa yeast growth increases by about 30to a 1 tesla field and the production of CO2 increases by about 30of yeast metabolism may be due to an increase in intercellular interaction and protein channel alignment, the introduction of an alteration in the DNA from the magnetic field exposure or a combination of these mechanisms. We also have found that the application of high magnetic fields (1 tesla and above) can have marked effects on the germination and growth of plants, especially corn, beans and peas. This finding has opened up the possibility of technology developments in botanical growth systems to accelerate seed germination and crop harvesting. Most recently we have investigated the application of high magnetic fields on leukemia, CaCoII and HEP G2 cancer cell lines. We found that when leukemia are exposed to a 12 tesla field for 2 hours has an increase in cell death by about 30that were not exposed to the magnetic field. Viability of CaCoII cells sandwiched between permanent magnets of maximum strength of 1.2 tesla was measured. A decrease in viable cells by 33unexposed cells. HSP 70 was measured for HEPG2 cells that were exposed to permanent magnetic field of 1.2 tesla for 40 minutes and for unexposed cells. It was found that the exposed cells produce 19 times more HSP70 compared to unexposed cells. Our results together with other investigators report suggest a strong evidence of a reduction in the cell growth rate for cancer cells when

  10. Quantitation of 4,4′-methylene diphenyl diisocyanate human serum albumin adducts

    Directory of Open Access Journals (Sweden)

    Leah G. Luna

    2014-01-01

    Full Text Available 4,4′-Methylene diphenyl diisocyanate (herein 4,4′-MDI is used in the production of polyurethane foams, elastomers, coatings, adhesives and the like for a wide range of commercial products. Occupational exposure to MDI levels above current airborne exposure limits can elicit immune mediated hypersensitivity reactions such as occupational asthma in sensitive individuals. To accurately determine exposure, there has been increasing interest in developing analytical methods to measure internal biomarkers of exposure to MDI. Previous investigators have reported methodologies for measuring MDI diamine metabolites and MDI-Lysine (4,4′-MDI-Lys adducts. The purpose of this study was to develop and validate an ultra performance liquid chromatography isotope dilution tandem mass spectrometry (UPLC-ID/MS/MS quantitation method via a signature peptide approach to enable biomonitoring of 4,4′-MDI adducted to human serum albumin (HSA in plasma. A murine, anti-4,4′-MDI monoclonal IgM antibody was bound to magnetic beads and utilized for enrichment of the MDI adducted HSA. Following enrichment, trypsin digestion was performed to generate the expected 414 site (primary site of adduction 4,4′-MDI-adducted HSA signature peptide that was quantified by UPLC-ID/MS/MS. An Agilent 6530 UPLC/quadrupole time of flight MS (QTOF system was utilized for intact adducted protein analysis and an Agilent 6490 UPLC/MS/MS system operated in multiple reaction monitoring (MRM mode was utilized for quantification of the adducted signature peptide biomarker both for in chemico and worker serum samples. Worker serum samples were initially screened utilizing the previously developed 4,4′-MDI-Lys amino acid method and results showed that 12 samples were identified as quantifiable for 4,4′-MDI-Lys adducts. The signature peptide adduct approach was applied to the 12 worker samples identified as quantifiable for 4,4′-MDI-Lys adducts. Results indicated no positive results

  11. Allee effects in tritrophic food chains: some insights in pest biological control.

    Science.gov (United States)

    Costa, Michel Iskin da S; Dos Anjos, Lucas

    2016-12-01

    Release of natural enemies to control pest populations is a common strategy in biological control. However, its effectiveness is supposed to be impaired, among other factors, by Allee effects in the biological control agent and by the fact that introduced pest natural enemies interact with some native species of the ecosystem. In this work, we devise a tritrophic food chain model where the assumptions previously raised are proved correct when a hyperpredator attacks the introduced pest natural enemy by a functional response type 2 or 3. Moreover, success of pest control is shown to be related to the release of large amounts (i.e., inundative releases) of natural enemies.

  12. Liquid chromatography-thermospray mass spectrometry of DNA adducts formed with mitomycin C, porfiromycin and thiotepa.

    Science.gov (United States)

    Musser, S M; Pan, S S; Callery, P S

    1989-07-14

    High-performance liquid chromatography (HPLC) and thermospray mass spectrometry were combined for the analysis of DNA adducts formed from the interaction of the anticancer drugs mitomycin C, porfiromycin and thiotepa with calf thymus DNA. The adducts formed from reaction of mitomycin C and porfiromycin with DNA were separated from unmodified nucleosides by HPLC on a C18 column and identified by thermospray mass spectrometry. Thiotepa DNA adducts readily depurinated from DNA and were chromatographed and identified by thermospray liquid chromatography-mass spectrometry as the modified bases without the ribose moiety attached. The utility of thermospray mass spectrometry for the identification of microgram quantities of nucleoside adducts and depurinated base adducts of these anticancer drugs was demonstrated.

  13. Study of complex matrix effect on solid phase microextraction for biological sample analysis.

    Science.gov (United States)

    Jiang, Ruifen; Xu, Jianqiao; Zhu, Fang; Luan, Tiangang; Zeng, Feng; Shen, Yong; Ouyang, Gangfeng

    2015-09-11

    Solid phase microextraction (SPME) has become a useful tool for in vivo monitoring the behavior of environmental organic pollutants in biological species due to its simplicity, relatively non-invasive, and cost-effective manner. However, the complex matrices in biological samples could significantly influence the extraction kinetic, and bias the quantification result. In this study, we investigated the effect of complex matrix on the extraction kinetic of SPME for biological sample analysis. Two sample matrices, phosphate-buffered saline (PBS) with bovine serum albumin (BSA) and agarose gel with BSA were used to simulate the biological fluid and tissue. Results showed that the addition of BSA significantly enhanced the mass transfer of organic compounds onto SPME fiber in both PBS buffer and gel sample. Enhancement factors ranging from 1.3 to 27, and 2.0 to 80 were found for all selected polyaromatic hydrocarbons (PAHs) in PBS buffer and agarose gel with BSA concentration of 0.1-5%, respectively. Then, an improved theoretical model was applied to quantify the observed enhancement effect, and the result showed that the predicted sampling time constant agreed well with the experimental one in complex matrix. Furthermore, a simplified equation was proposed for the real biological sample analysis.

  14. Nonlinear effects of the finite amplitude ultrasound wave in biological tissues

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Nonlinear effects will occur during the transmission of the finite amplitude wave in biological tissues.The theoretical prediction and experimental demonstration of the nonlinear effects on the propagation of the finite amplitude wave at the range of biomedical ultrasound frequency and intensity are studied.Results show that the efficiency factor and effective propagation distance will decrease while the attenuation coefficient increases due to the existence of nonlinear effects.The experimental results coincided quite well with the theory.This shows that the effective propagation distance and efficiency factor can be used to describe quantitatively the influence of nonlinear effects on the propagation of the finite amplitude sound wave in biological tissues.

  15. ICBEN review of research on the biological effects of noise 2011-2014.

    Science.gov (United States)

    Basner, Mathias; Brink, Mark; Bristow, Abigail; de Kluizenaar, Yvonne; Finegold, Lawrence; Hong, Jiyoung; Janssen, Sabine A; Klaeboe, Ronny; Leroux, Tony; Liebl, Andreas; Matsui, Toshihito; Schwela, Dieter; Sliwinska-Kowalska, Mariola; Sörqvist, Patrik

    2015-01-01

    The mandate of the International Commission on Biological Effects of Noise (ICBEN) is to promote a high level of scientific research concerning all aspects of noise-induced effects on human beings and animals. In this review, ICBEN team chairs and co-chairs summarize relevant findings, publications, developments, and policies related to the biological effects of noise, with a focus on the period 2011-2014 and for the following topics: Noise-induced hearing loss; nonauditory effects of noise; effects of noise on performance and behavior; effects of noise on sleep; community response to noise; and interactions with other agents and contextual factors. Occupational settings and transport have been identified as the most prominent sources of noise that affect health. These reviews demonstrate that noise is a prevalent and often underestimated threat for both auditory and nonauditory health and that strategies for the prevention of noise and its associated negative health consequences are needed to promote public health.

  16. Waist circumference as a mediator of biological maturation effect on the motor coordination in children

    Science.gov (United States)

    Luz, Leonardo G.O.; Seabra, André; Padez, Cristina; Duarte, João P.; Rebelo-Gonçalves, Ricardo; Valente-dos-Santos, João; Luz, Tatiana D.D.; Carmo, Bruno C.M.; Coelho-e-Silva, Manuel

    2016-01-01

    Abstract Objective: The present study aimed to: 1) examine the association of biological maturation effect on performance at a motor coordination battery and 2) to assess whether the association between biological maturation and scores obtained in motor coordination tests is mediated by some anthropometric measurement. Methods: The convenience sample consisted of 73 male children aged 8 years old. Anthropometric data considered the height, body mass, sitting height, waist circumference, body mass index, fat mass and fat-free mass estimates. Biological maturation was assessed by the percentage of the predicted mature stature. Motor coordination was tested by the Körperkoordinationstest für Kinder. A partial correlation between anthropometric measurements, z-score of maturation and the motor coordination tests were performed, controlling for chronological age. Finally, causal mediation analysis was performed. Results: Height, body mass, waist circumference and fat mass showed a slight to moderate inverse correlation with motor coordination. Biological maturation was significantly associated with the balance test with backward walking (r=-0.34). Total mediation of the waist circumference was identified in the association between biological maturation and balance test with backward walking (77%). Conclusions: We identified an association between biological maturation and KTK test performance in male children and also verified that there is mediation of waist circumference. It is recommended that studies be carried out with female individuals and at other age ranges. PMID:26972616

  17. Effective identification of conserved pathways in biological networks using hidden Markov models.

    Directory of Open Access Journals (Sweden)

    Xiaoning Qian

    Full Text Available BACKGROUND: The advent of various high-throughput experimental techniques for measuring molecular interactions has enabled the systematic study of biological interactions on a global scale. Since biological processes are carried out by elaborate collaborations of numerous molecules that give rise to a complex network of molecular interactions, comparative analysis of these biological networks can bring important insights into the functional organization and regulatory mechanisms of biological systems. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we present an effective framework for identifying common interaction patterns in the biological networks of different organisms based on hidden Markov models (HMMs. Given two or more networks, our method efficiently finds the top matching paths in the respective networks, where the matching paths may contain a flexible number of consecutive insertions and deletions. CONCLUSIONS/SIGNIFICANCE: Based on several protein-protein interaction (PPI networks obtained from the Database of Interacting Proteins (DIP and other public databases, we demonstrate that our method is able to detect biologically significant pathways that are conserved across different organisms. Our algorithm has a polynomial complexity that grows linearly with the size of the aligned paths. This enables the search for very long paths with more than 10 nodes within a few minutes on a desktop computer. The software program that implements this algorithm is available upon request from the authors.

  18. Waist circumference as a mediator of biological maturation effect on the motor coordination in children

    Directory of Open Access Journals (Sweden)

    Leonardo G.O. Luz

    Full Text Available Abstract Objective: The present study aimed to: 1 examine the association of biological maturation effect on performance at a motor coordination battery and 2 to assess whether the association between biological maturation and scores obtained in motor coordination tests is mediated by some anthropometric measurement. Methods: The convenience sample consisted of 73 male children aged 8 years old. Anthropometric data considered the height, body mass, sitting height, waist circumference, body mass index, fat mass and fat-free mass estimates. Biological maturation was assessed by the percentage of the predicted mature stature. Motor coordination was tested by the Körperkoordinationstest für Kinder. A partial correlation between anthropometric measurements, z-score of maturation and the motor coordination tests were performed, controlling for chronological age. Finally, causal mediation analysis was performed. Results: Height, body mass, waist circumference and fat mass showed a slight to moderate inverse correlation with motor coordination. Biological maturation was significantly associated with the balance test with backward walking (r=-0.34. Total mediation of the waist circumference was identified in the association between biological maturation and balance test with backward walking (77%. Conclusions: We identified an association between biological maturation and KTK test performance in male children and also verified that there is mediation of waist circumference. It is recommended that studies be carried out with female individuals and at other age ranges.

  19. Neutron exposures in human cells: bystander effect and relative biological effectiveness.

    Directory of Open Access Journals (Sweden)

    Isheeta Seth

    Full Text Available Bystander effects have been observed repeatedly in mammalian cells following photon and alpha particle irradiation. However, few studies have been performed to investigate bystander effects arising from neutron irradiation. Here we asked whether neutrons also induce a bystander effect in two normal human lymphoblastoid cell lines. These cells were exposed to fast neutrons produced by targeting a near-monoenergetic 50.5 MeV proton beam at a Be target (17 MeV average neutron energy, and irradiated-cell conditioned media (ICCM was transferred to unirradiated cells. The cytokinesis-block micronucleus assay was used to quantify genetic damage in radiation-naïve cells exposed to ICCM from cultures that received 0 (control, 0.5, 1, 1.5, 2, 3 or 4 Gy neutrons. Cells grown in ICCM from irradiated cells showed no significant increase in the frequencies of micronuclei or nucleoplasmic bridges compared to cells grown in ICCM from sham irradiated cells for either cell line. However, the neutron beam has a photon dose-contamination of 5%, which may modulate a neutron-induced bystander effect. To determine whether these low doses of contaminating photons can induce a bystander effect, cells were irradiated with cobalt-60 at doses equivalent to the percent contamination for each neutron dose. No significant increase in the frequencies of micronuclei or bridges was observed at these doses of photons for either cell line when cultured in ICCM. As expected, high doses of photons induced a clear bystander effect in both cell lines for micronuclei and bridges (p<0.0001. These data indicate that neutrons do not induce a bystander effect in these cells. Finally, neutrons had a relative biological effectiveness of 2.0 ± 0.13 for micronuclei and 5.8 ± 2.9 for bridges compared to cobalt-60. These results may be relevant to radiation therapy with fast neutrons and for regulatory agencies setting standards for neutron radiation protection and safety.

  20. Line narrowing spectroscopic studies of DNA-carcinogen adducts and DNA-dye complexes

    Energy Technology Data Exchange (ETDEWEB)

    Suh, Myungkoo [Iowa State Univ., Ames, IA (United States)

    1995-12-06

    Laser-induced fluorescence line narrowing and non-line narrowing spectroscopic methods were applied to conformational studies of stable DNA adducts of the 7β, 8α-dihydoxy-9α, l0α-epoxy-7,8,9, 10-tetrahydrobenzo[α]pyrene (anti-BPDE). Stereochemically distinct (+)-trans-, (-)-trans-, (+)-cis- and (-)-cis adducts of anti-BPDE bound to exocyclic amino group of the central guanine in an 11-mer oligonucleotide, exist in a mixture of conformations in frozen aqueous buffer matrices. The (+)-trans adduct adopts primarily an external conformation with a smaller fraction ( ~25 %) exists in a partially base-stacked conformation. Both cis adducts were found to be intercalated with significant π-π stacking interactions between the pyrenyl residues and the bases. Conformations of the trans-adduct of (+)-anti -BPDE in 11-mer oligonucleotides were studied as a function of flanking bases. In single stranded form the adduct at G2 or G3 (5 ft-flanking, base guanine) adopts a conformation with strong, interaction with the bases. In contrast, the adduct with a 5ft-flanking, thymine exists in a primarily helixexternal conformation. Similar differences were observed in the double stranded oligonucleotides. The nature of the 3ft-flanking base has little influence on the conformational equilibrium of the (+)-trans-anti BPDE-dG adduct. The formation and repair of BPDE-N2-dG in DNA isolated from the skin of mice treated topically with benzo[α]pyrene (BP) was studied. Low-temperature fluorescence spectroscopy of the intact DNA identified the major adduct as (+)-trans-anti-BPDE-N-dG, and the minor adduct fraction consisted mainly of (+)-cis-anti-BPDE-N2-dG.

  1. Line narrowing spectroscopic studies of DNA-carcinogen adducts and DNA-dye complexes

    Energy Technology Data Exchange (ETDEWEB)

    Suh, Myungkoo

    1995-12-06

    Laser-induced fluorescence line narrowing and non-line narrowing spectroscopic methods were applied to conformational studies of stable DNA adducts of the 7{beta}, 8{alpha}-dihydoxy-9{alpha}, l0{alpha}-epoxy-7,8,9, 10-tetrahydrobenzo[{alpha}]pyrene (anti-BPDE). Stereochemically distinct (+)-trans-, ({minus})-trans-, (+)-cis- and ({minus})-cis adducts of anti-BPDE bound to exocyclic amino group of the central guanine in an 11-mer oligonucleotide, exist in a mixture of conformations in frozen aqueous buffer matrices. The (+)-trans adduct adopts primarily an external conformation with a smaller fraction ( {approximately} 25 %) exists in a partially base-stacked conformation. Both cis adducts were found to be intercalated with significant {pi}-{pi} stacking interactions between the pyrenyl residues and the bases. Conformations of the trans-adduct of (+)-anti -BPDE in 11-mer oligonucleotides were studied as a function of flanking bases. In single stranded form the adduct at G{sub 2} or G{sub 3} (5 ft-flanking, base guanine) adopts a conformation with strong, interaction with the bases. In contrast, the adduct with a 5ft-flanking, thymine exists in a primarily helixexternal conformation. Similar differences were observed in the double stranded oligonucleotides. The nature of the 3ft-flanking base has little influence on the conformational equilibrium of the (+)-trans-anti BPDE-dG adduct. The formation and repair of BPDE-N{sup 2}-dG in DNA isolated from the skin of mice treated topically with benzo[{alpha}]pyrene (BP) was studied. Low-temperature fluorescence spectroscopy of the intact DNA identified the major adduct as (+)-trans-anti-BPDE-N-dG, and the minor adduct fraction consisted mainly of (+)-cis-anti-BPDE-N{sup 2}-dG.

  2. Methods for studying and criteria for evaluating the biological effects of electric fields of industrial frequency

    Energy Technology Data Exchange (ETDEWEB)

    Savin, B.M.; Shandala, M.G.; Nikonova, K.V.; Morozov, Yu.A.

    1978-10-01

    Data are reviewed from a number of USSR research studies on the biological effects of electric power transmission lines of 1150 Kv and above. Effects on man, plants, animals, and terrestrial ecosystems are reported. Existing health standards in the USSR for the exposure of personnel working in electric fields are included. It is concluded that high-voltage electric fields have a harmful effect on man and his environment.

  3. A Synthetic Aptamer-Drug Adduct for Targeted Liver Cancer Therapy.

    Science.gov (United States)

    Trinh, Thu Le; Zhu, Guizhi; Xiao, Xilin; Puszyk, William; Sefah, Kwame; Wu, Qunfeng; Tan, Weihong; Liu, Chen

    2015-01-01

    AS1411 (previously known as AGRO100) is a 26 nucleotide guanine-rich DNA aptamer which forms a guanine quadruplex structure. AS1411 has shown promising utility as a treatment for cancers in Phase I and Phase II clinical trials without causing major side-effects. AS1411 inhibits tumor cell growth by binding to nucleolin which is aberrantly expressed on the cell membrane of many tumors. In this study, we utilized a simple technique to conjugate a widely-used chemotherapeutic agent, doxorubicin (Dox), to AS1411 to form a synthetic Drug-DNA Adduct (DDA), termed as AS1411-Dox. We demonstrate the utility of AS1411-Dox in the treatment of hepatocellular carcinoma (HCC) by evaluating the targeted delivery of Dox to Huh7 cells in vitro and in a murine xenograft model of HCC.

  4. A Synthetic Aptamer-Drug Adduct for Targeted Liver Cancer Therapy.

    Directory of Open Access Journals (Sweden)

    Thu Le Trinh

    Full Text Available AS1411 (previously known as AGRO100 is a 26 nucleotide guanine-rich DNA aptamer which forms a guanine quadruplex structure. AS1411 has shown promising utility as a treatment for cancers in Phase I and Phase II clinical trials without causing major side-effects. AS1411 inhibits tumor cell growth by binding to nucleolin which is aberrantly expressed on the cell membrane of many tumors. In this study, we utilized a simple technique to conjugate a widely-used chemotherapeutic agent, doxorubicin (Dox, to AS1411 to form a synthetic Drug-DNA Adduct (DDA, termed as AS1411-Dox. We demonstrate the utility of AS1411-Dox in the treatment of hepatocellular carcinoma (HCC by evaluating the targeted delivery of Dox to Huh7 cells in vitro and in a murine xenograft model of HCC.

  5. Determination of hemoglobin adduct of a musk xylene metabolite in trout as biomarker of exposure by gas chromatography mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    MOTTALEB Mohammad Abdul; KARIM Mohammad Rezaul

    2005-01-01

    Musk xylene(MX) is frequently used as fragrances in formulation of personal care products. Quantification of a bound 4-aminoMX(4-AMX) as cysteine adducts in trout hemoglobin(Hb) was made by gas chromatography-ion trap-mass spectrometry(GC/MS). The Hb samples were collected from trout after 24 h exposure to MX at 10 μg/g, and or menhaden oil(control). The formation of cysteine-Hb adduct was observed from nitroso derivative of MX, released by alkaline hydrolysis. The released 4-AMX metabolite was extracted in nhexane. The extract was then reduced by evaporation, and analyzed by GC/MS. When similar agreement of mass spectral features and retention time of 4-AMX were obtained in both standard and sample solutions, the presence of 4-AMX metabolite in the Hb was confirmed.The concentration of 4-AMX was found to be 3.1 x 10-6- 6.9 x 10-6 mg/g in the Hb solution. Quantitation was made based on an internal standard, a calibration plot, and response factor. In the non-hydrolyzed and laboratory blank extracts, the 4-AMX metabolite was not detected. Additionally, coeluting and interfering ions were observed in the biological samples.

  6. Predator interference effects on biological control: The "paradox" of the generalist predator revisited

    Science.gov (United States)

    Parshad, Rana D.; Bhowmick, Suman; Quansah, Emmanuel; Basheer, Aladeen; Upadhyay, Ranjit Kumar

    2016-10-01

    An interesting conundrum in biological control questions the efficiency of generalist predators as biological control agents. Theory suggests, generalist predators are poor agents for biological control, primarily due to mutual interference. However field evidence shows they are actually quite effective in regulating pest densities. In this work we provide a plausible answer to this paradox. We analyze a three species model, where a generalist top predator is introduced into an ecosystem as a biological control, to check the population of a middle predator, that in turn is depredating on a prey species. We show that the inclusion of predator interference alone, can cause the solution of the top predator equation to blow-up in finite time, while there is global existence in the no interference case. This result shows that interference could actually cause a population explosion of the top predator, enabling it to control the target species, thus corroborating recent field evidence. Our results might also partially explain the population explosion of certain species, introduced originally for biological control purposes, such as the cane toad (Bufo marinus) in Australia, which now functions as a generalist top predator. We also show both Turing instability and spatio-temporal chaos in the model. Lastly we investigate time delay effects.

  7. Biologically templated assembly of hybrid semiconducting nanomesh for high performance field effect transistors and sensors

    Science.gov (United States)

    Byeon, Hye-Hyeon; Lee, Seung-Woo; Lee, Eun-Hee; Kim, Woong; Yi, Hyunjung

    2016-10-01

    Delicately assembled composites of semiconducting nanomaterials and biological materials provide an attractive interface for emerging applications, such as chemical/biological sensors, wearable health monitoring devices, and therapeutic agent releasing devices. The nanostructure of composites as a channel and a sensing material plays a critical role in the performance of field effect transistors (FETs). Therefore, it is highly desirable to prepare elaborate composite that can allow the fabrication of high performance FETs and also provide high sensitivity and selectivity in detecting specific chemical/biological targets. In this work, we demonstrate that high performance FETs can be fabricated with a hydrodynamically assembled composite, a semiconducting nanomesh, of semiconducting single-walled carbon nanotubes (S-SWNTs) and a genetically engineered M13 phage to show strong binding affinity toward SWNTs. The semiconducting nanomesh enables a high on/off ratio (~104) of FETs. We also show that the threshold voltage and the channel current of the nanomesh FETs are sensitive to the change of the M13 phage surface charge. This biological gate effect of the phage enables the detection of biologically important molecules such as dopamine and bisphenol A using nanomesh-based FETs. Our results provide a new insight for the preparation of composite material platform for highly controllable bio/electronics interfaces.

  8. Biologically templated assembly of hybrid semiconducting nanomesh for high performance field effect transistors and sensors

    Science.gov (United States)

    Byeon, Hye-Hyeon; Lee, Seung-Woo; Lee, Eun-Hee; Kim, Woong; Yi, Hyunjung

    2016-01-01

    Delicately assembled composites of semiconducting nanomaterials and biological materials provide an attractive interface for emerging applications, such as chemical/biological sensors, wearable health monitoring devices, and therapeutic agent releasing devices. The nanostructure of composites as a channel and a sensing material plays a critical role in the performance of field effect transistors (FETs). Therefore, it is highly desirable to prepare elaborate composite that can allow the fabrication of high performance FETs and also provide high sensitivity and selectivity in detecting specific chemical/biological targets. In this work, we demonstrate that high performance FETs can be fabricated with a hydrodynamically assembled composite, a semiconducting nanomesh, of semiconducting single-walled carbon nanotubes (S-SWNTs) and a genetically engineered M13 phage to show strong binding affinity toward SWNTs. The semiconducting nanomesh enables a high on/off ratio (~104) of FETs. We also show that the threshold voltage and the channel current of the nanomesh FETs are sensitive to the change of the M13 phage surface charge. This biological gate effect of the phage enables the detection of biologically important molecules such as dopamine and bisphenol A using nanomesh-based FETs. Our results provide a new insight for the preparation of composite material platform for highly controllable bio/electronics interfaces. PMID:27762315

  9. Biologically effective doses of postoperative radiotherapy in the prevention of keloids. Dose-effect relationship

    Energy Technology Data Exchange (ETDEWEB)

    Kal, H.B.; Veen, R.E. [University Medical Center Utrecht (Netherlands). Dept. of Radiotherapy

    2005-11-01

    Purpose: To review the recurrence rates of keloids after surgical excision followed by radiotherapy, and to answer the question whether after normalization of the dose, a dose-effect relationship could be derived. Material and Methods: A literature search was performed to identify studies dealing with the efficacy of various irradiation regimes for the prevention of keloids after surgery. Biologically effective doses (BEDs) of the various irradiation regimens were calculated using the linear-quadratic concept. A distinction between recurrence rates of keloids in the face and neck region and those in other parts of the body was made. Results: 31 reports were identified with PubMed with the search terms keloids, surgery, radiation therapy, radiotherapy. 13 reports were excluded, because no link could be found between recurrence rate and dose, or if less than ten patients per dose group. The recurrence rate for surgery only was 50-80%. For BED values >10 Gy the recurrence rate decreased as a function of BED. For BED values >30 Gy the recurrence rate was <10%. For a given dose, the recurrence rates of keloids in the sites with high stretch tension were not significantly higher than in sites without stretch tension. Conclusion: The results of this study indicate that for effectively treating keloids postoperatively, a relatively high dose must be applied in a short overall treatment time. The optimal treatment probably is an irradiation scheme resulting in a BED value of at least 30 Gy. A BED value of 30 Gy can be obtained with, for instance, a single acute dose of 13 Gy, two fractions of 8 Gy two fractions of 8 Gy or three fractions of 6 Gy, or a single dose of 27 Gy at low dose rate. The radiation treatment should be administered within 2 days after surgery. (orig.)

  10. Effects of Developed Electronic Instructional Medium on Students' Achievement in Biology

    Science.gov (United States)

    Chinna, Nsofor Caroline; Dada, Momoh Gabriel

    2013-01-01

    The study investigated the effects of developed electronic instructional medium (video DVD instructional package) on students' achievement in Biology. It was guided by two research questions and two hypotheses, using a quasi-experimental, pretest-postest control group design. The sample comprised of 180 senior secondary, year two students from six…

  11. Static magnetic fields: A summary of biological interactions, potential health effects, and exposure guidelines

    Energy Technology Data Exchange (ETDEWEB)

    Tenforde, T.S.

    1992-05-01

    Interest in the mechanisms of interaction and the biological effects of static magnetic fields has increased significantly during the past two decades as a result of the growing number of applications of these fields in research, industry and medicine. A major stimulus for research on the bioeffects of static magnetic fields has been the effort to develop new technologies for energy production and storage that utilize intense magnetic fields (e.g., thermonuclear fusion reactors and superconducting magnet energy storage devices). Interest in the possible biological interactions and health effects of static magnetic fields has also been increased as a result of recent developments in magnetic levitation as a mode of public transportation. In addition, the rapid emergence of magnetic resonance imaging as a new clinical diagnostic procedure has, in recent years, provided a strong rationale for defining the possible biological effects of magnetic fields with high flux densities. In this review, the principal interaction mechanisms of static magnetic fields will be described, and a summary will be given of the present state of knowledge of the biological, environmental, and human health effects of these fields.

  12. Biological effects from electric fields associated with high voltage transmission lines

    Energy Technology Data Exchange (ETDEWEB)

    1983-11-01

    Efforts during the past year by the US Department of Energy and the Electric Power Research Institute-funded laboratories to investigate the biological effects from electric fields are described in resume form. Investigations generally have been summarized with objectives, accomplishments of the past year, and some indication of projected studies.

  13. The Effectiveness of a Virtual Field Trip (VFT) Module in Learning Biology

    Science.gov (United States)

    Haris, Norbaizura; Osman, Kamisah

    2015-01-01

    Virtual Field Trip is a computer aided module of science developed to study the Colonisation and Succession in Mangrove Swamps, as an alternative to the real field trip in Form for Biology. This study is to identify the effectiveness of the Virtual Field Trip (VFT) module towards the level of achievement in the formative test for this topic. This…

  14. Effectiveness of Blended Cooperative Learning Environment in Biology Teaching: Classroom Community Sense, Academic Achievement and Satisfaction

    Science.gov (United States)

    Yapici, I. Ümit

    2016-01-01

    The aim of this study was to examine the effect of Blended Cooperative Learning Environment (BCLE) in biology teaching on students' classroom community sense, their academic achievement and on their levels of satisfaction. In the study, quantitative and qualitative research methods were used together. The study was carried out with 30 students in…

  15. Biological assessment of effects of combined sewer overflows and storm water discharges.

    NARCIS (Netherlands)

    Lijklema, L.; Roijackers, R.M.M.; Cuppen, J.G.M.

    1989-01-01

    The biological effects of discharges from combined or separated sewer systems are difficult to assess or to predict due to variahilities in concentrations, environmental conditions, morphometry, susceptibility of organisms, seasonality and other factors. A general discussion of the problem results i

  16. Simulation of the radiation effects on biological objects; Simulation der Strahlenwirkung auf biologische Objekte

    Energy Technology Data Exchange (ETDEWEB)

    Bug, Marion; Nettelbeck, Heidi [Physikalisch-Technische Bundesanstalt (PTB), Braunschweig (Germany). Arbeitsgruppe ' Biologische Wirksamkeit Ionisierender Strahlung'

    2013-06-15

    The simulation of biological radiation effects by means of the electron transport in water and DNA and the cross sections for elastic scattering, electronic excitation, and ionization in electron collisions with tetrahydrofuran molecules is described, whereby the strand-breaking probabilities are determined. (HSI)

  17. Effects of organic versus conventional management on chemical and biological parameters in agricultural soils

    NARCIS (Netherlands)

    Diepeningen, van A.D.; Vos, de O.J.; Korthals, G.W.; Bruggen, van A.H.C.

    2006-01-01

    A comparative study of organic and conventional arable farming systems was conducted in The Netherlands to determine the effect of management practices on chemical and biological soil properties and soil health. Soils from thirteen accredited organic farms and conventionally managed neighboring farm

  18. Effectiveness of the Biology PTechLS Module in a Felda Science Centre

    Science.gov (United States)

    Alias, Norlidah; DeWitt, Dorothy; Rahman, Mohd Nazri Abdul; Gelamdin, Rashidah Begum; Rauf, Rose Amnah Abd; Siraj, Saedah

    2014-01-01

    The PTechLS module combines learning styles with the use of technology to increase students' learning experience, especially in learning abstract concepts. The PTechLS module prototype was developed by Norlidah Alias (2010). The aim of this study is to evaluate the implementation effectiveness of the Biology PTechLS module in a Felda Learning…

  19. Why magnetic and electromagnetic effects in biology are irreproducible and contradictory?

    Science.gov (United States)

    Buchachenko, Anatoly

    2016-01-01

    The main source of magnetic and electromagnetic effects in biological systems is now generally accepted and demonstrated in this paper to be radical pair mechanism which implies pairwise generation of radicals in biochemical reactions. This mechanism was convincingly established for enzymatic adenosine triphosphate (ATP) and desoxynucleic acid (DNA) synthesis by using catalyzing metal ions with magnetic nuclei ((25)Mg, (43)Ca, (67)Zn) and supported by magnetic field effects on these reactions. The mechanism, is shown to function in medicine as a medical remedy or technology (trans-cranial magnetic stimulation, nuclear magnetic control of the ATP synthesis in heart muscle, the killing of cancer cells by suppression of DNA synthesis). However, the majority of magnetic effects in biology remain to be irreproducible, contradictory, and enigmatic. Three sources of such a state are shown in this paper to be: the presence of paramagnetic metal ions as a component of enzymatic site or as an impurity in an uncontrollable amount; the property of the radical pair mechanism to function at a rather high concentration of catalyzing metal ions, when at least two ions enter into the catalytic site; and the kinetic restrictions, which imply compatibility of chemical and spin dynamics in radical pair. It is important to keep in mind these factors to properly understand and predict magnetic effects in magneto-biology and biology itself and deliberately use them in medicine.

  20. Risk of serious adverse effects of biological and targeted drugs in patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Tarp, Simon; Eric Furst, Daniel; Boers, Maarten

    2016-01-01

    OBJECTIVES: To determine possible differences in serious adverse effects among the 10 currently approved biological and targeted synthetic DMARDs (b/ts-DMARDs) for RA. METHODS: Systematic review in bibliographic databases, trial registries and websites of regulatory agencies identified randomized...... differences in rates of SAEs. Our data suggest caution should be taken when deciding among available drugs. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42014014842....

  1. Effect of temperature on the biology of Paracoccus marginatus Williams and Granara de Willink (Homoptera: Pseudococcidae).

    Science.gov (United States)

    Abstract: Effect of temperature on the biology of Paracoccus marginatus was investigated. P. marginatus was able to develop and complete its life cycle at 18°, 20°, 25° and 30°C. At 15°, 34° and 35°C eggs hatched, but further development was arrested. Approximately 80 -90% of the eggs survived betw...

  2. Genetic polymorphisms in biotransformation enzymes for benzo[a]pyrene and related levels of benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts in Goeckerman therapy.

    Science.gov (United States)

    Beranek, Martin; Fiala, Zdenek; Kremlacek, Jan; Andrys, Ctirad; Hamakova, Kvetoslava; Chmelarova, Marcela; Palicka, Vladimir; Borska, Lenka

    2016-07-25

    Goeckerman therapy (GT) for psoriasis combines the therapeutic effect of crude coal tar (CCT) and ultraviolet radiation (UVR). CCT contains polycyclic aromatic hydrocarbons, some of which can form DNA adducts that may induce mutations and contribute to carcinogenesis. The aim of our work was to evaluate the relationship between concentrations of benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts (BPDE-DNA adducts) and rs4646903 (CYP1A1 gene), rs1048943 (CYP1A1), rs1056836 (CYP1B1), rs1051740 (EPHX1), rs2234922 (EPHX1) and rs8175347 (UGT1A1) polymorphic sites, and GSTM1 null polymorphism in 46 patients with chronic stable plaque psoriasis who underwent GT. The level of BPDE-DNA adducts was determined using the OxiSelect BPDE-DNA Adduct ELISA Kit. Polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (rs4646903, rs1048943, rs1051740, and rs2234922), fragment analysis (rs8175347), real-time PCR (rs1056836), and digital droplet PCR polymorphism (GSTM1) were used. CYP1B1*1/*1 wild-type subjects and CYP1B1*3/*1 heterozygotes for rs1056836 formed significantly higher amounts of BPDE-DNA adducts than CYP1B1*3/*3 homozygotes (p=0.031 and p=0.005, respectively). Regarding rs1051740, individuals with EPHX1*3/*1 heterozygosity revealed fewer adducts than EPHX1*1/*1 wild-type subjects (p=0.026). Our data suggest that CYP1B1/EPHX1 genotyping could help to predict the risk of DNA damage and to optimize doses of coal tar and UVR exposure in psoriatic patients in whom GT was applied.

  3. EFFECTS OF POLLUTANTS ON BIOLOGICAL SYSTEMS. CHAPTER FROM THE ENERGY AND ENVIRONMENT DIVISION ANNUAL REPORT 1979

    Energy Technology Data Exchange (ETDEWEB)

    Authors, Various

    1980-10-01

    Planning a rational energy future requires anticipating the environmental consequences of various technologies. This is difficult to do with precision as the effects of pollutants are often determined by interactions between and among complex physical (abiotic) and biological (biotic) systems. A given pollutant may affect human beings through direct exposure or indirectly through inducing changes to biological systems which humans need to utilize. The concentration of a toxin in the food chain or the destruction of organisms necessary for the maintenance of high quality water are examples of indirect effects. Pollutants can be transformed and/or degraded as they establish residence in various components of an ecosystem. Anticipation and amelioration of pollutant effects involves the integration of a vast range of data. This data includes: (1) physical and chemical characterization cf the pollutant as it enters the environment; (2) determining effects on the various components (biotic and abiotic) within the context of the functioning ecosystem of interest; (3) transformation in movements and/or degradation of the pollutant within that ecosystem and within specific organisms and physical components; and (4) determining a detailed biochemical and biological picture of the interactions of pollutants with particular organisms and/or their cellular components judged salient for various processes. The major programs described below are designed to answer parts of the above fundamental questions relevant to pollutants generated by energy related technologies. Their emphasis is on anticipating consequences to the biological components of various ecosystems. The work ranges from studies involving parts of a single cell (the membranes) to studies involving the whole ecosystem (in the pelagic zone of a lake). The programs take advantage of expertise and technical abilities present at LBL. Two small exploratory projects which were of brief duration and not related to

  4. STUDY ON THE RELATIONSHIP OF ARSENIC TRIOXIDE-INDUCED BIOLOGICAL EFFECTS AND DEGRADATIONOF PML PROTEINS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To understand whether arsenic trioxide (As2O3)-induced biological effects are associated with degradation of PML proteins. Methods Acute promyelocytic leukemia (APL) cell line NB4, acute T-lymphocytic leukemia cell line Jurkat, acute myeloid leukemia cell line U937, and chronic myelocytic leukemia blast crisis cell line K562 were used as in vitro models. In different cell lines, the As2O3-induced bio- logical effects were determined by cell growth, cell viability, cell morphology, and flow cytometry assay on sub- G1 cell content. The alteration of PML proteins was analyzed by immunofluorescence. Results In terms of growth inhibition and apoptosis induction, 1.0μmol/L As2O3 had different effects on different cell lines. However, degradation of PML proteins occurred in all the cell lines with As2O3 treatment. Conclusion As2O3-induced biological effects may be independent of PML protein degradation.

  5. Information on biological health effects of ionizing radiation and radionuclides: the rule of a web site

    Energy Technology Data Exchange (ETDEWEB)

    Comte, A.; Gaillard-Lecanu, E.; Flury-Herard, A. [CEA Fontenay aux Roses, 92 (France); Ourly, F. [CEA Saclay, 91 - Gif sur Yvette (France); Hemidy, P.; Lallemand, J. [Electricite de France (EDF), Service de Radioprotection, 75 - Paris (France)

    2006-07-01

    The purpose of this project is to provide a source of information on biological and health effects of radionuclides and ionizing radiation in an easy to use format. Reported work is made up of two distinct parts: data sheets for selected radionuclides and a web file. Data sheets: Specific radiation data sheets provide an overview of the properties, the environmental behaviour, the different pathways of human exposure and the biological and health consequences of selected radionuclides. Radionuclides that have been selected are those commonly dealt with in nuclear industry (and in other areas such as medicine) and released to the environment or naturally occurring (plutonium, tritium, carbon 14). Data sheets corresponding to the different radionuclides are based on the main sources of scientific information in dosimetry, epidemiology, radiobiology and radiation protection. These data sheets are intended for radiation protection specialists and physicians. They include: main physical and chemical characteristics, main radiation protection data: dose coefficients (public, workers), dose limits sources, total released estimate (nuclear industry, atmospheric tests, main pathway of human exposure and biological behaviour, biological and health effects, medical supervision, treatment a list of the main references, appendix providing accurate information. Web file: http://www-dsv.cea.fr/doc/carmin{sub e}xt/fond.php This web file provides a source of information on biological and health effects of ionizing radiation and biological basic knowledge of radiation protection. Available for consultation via Internet, compiled information provides, in a same file, subjects as varied as biological mechanisms, ionizing radiations action, biological and health effects, risk assessment This file is mainly intended to assist in informing and training of non-specialist readership (students, teaching on radiation protection basic knowledge. This electronic document is divided in three

  6. Status of study on biological and toxicological effects of nanoscale materials

    Institute of Scientific and Technical Information of China (English)

    WANG; Bing; FENG; Weiyue; ZHAO; Yuliang; XING; Gengmei; CH

    2005-01-01

    Because the physical and chemical properties of nanosized materials mostly differ from the existing microsized materials, their potential impacts on human health and the environment will be topics under the serious discussions in press and in a number of international scientific journals. We analyze and summarize the existing data of the experimental study on the biological activities and adverse effects of nanoscale materials/particles including single wall carbon nanotubes, multi wall carbon nanotubes, titanium oxide and iron powders. Though some biological behaviors of nanoscale materials observed cannot be understood on the basis of the current knowledge, as the existing data are mostly preliminary, it is too early to make some exclusive conclusions on biological activities (or the toxicity) of any of nanoscale materials. The experimental techniques, the current topics, and the future research directions for this new research field are also discussed.

  7. Biological effects of mercury pollution. (Latest citations from the NTIS bibliographic database). Published Search

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-08-01

    The bibliography contains citations concerning biological and biochemical effects of mercury pollutants on humans, animals, and plants. References cover long-term and short-term experiments, biochemical reaction kinetics, pollution sources, and ecosystems. Mercury poisoning, metabolism, and related diseases are described. Carcinogenicity testing, health risk and assessment, and the effects on food chains are examined. (Contains 50-250 citations and includes a subject term index and title list.) (Copyright NERAC, Inc. 1995)

  8. Biological effects of low-level exposures: a perspective from U.S. EPA scientists.

    OpenAIRE

    Davis, J M; Farland, W H

    1998-01-01

    Biological effects of low-level exposures (BELLE) may be very important in characterizing the potential health risks of environmental pollutants. Before some features of BELLE, such as effects that may be modulated by adaptive or defense mechanisms, can be taken into greater consideration in U.S. Environmental Protection Agency risk assessments, however adequate information on a toxicant's mode of action and answers to other questions are needed.

  9. Hemoglobin adducts of N-substituted aryl compounds in exposure control and risk assessment.

    Science.gov (United States)

    Neumann, H G; Birner, G; Kowallik, P; Schütze, D; Zwirner-Baier, I

    1993-03-01

    Arylamines, nitroarenes, and azo dyes yield a common type of metabolite, the nitroarene, which produces a hydrolyzable adduct with protein and is closely related to the critical, ultimate toxic and genotoxic metabolite. The target dose as measured by hemoglobin adducts in erythrocytes reflects not only the actual uptake from the environment but also an individual's capacity for metabolic activation and is therefore an improved dosimeter for human exposure. The usefulness of hemoglobin adducts in molecular epidemiology is now widely recognized. With regard to risk assessment, many questions need to be answered. The described experiments in rats address some of these questions. The relationship between binding to hemoglobin in erythrocytes and to proteins in plasma has been found to vary considerably for a number of diamines. The fraction of hydrolyzable adducts out of the total protein adducts formed also varies in both compartments. This indicates that the kind of circulating metabolites and their availability in different compartments is compound specific. This has to do with the complex pattern of competing metabolic pathways, and the role of N-acetylation and deacetylation is emphasized. An example of nonlinear dose dependence adds to the complexity. Analysis of hemoglobin adducts reveals interesting insights into prevailing pathways, which not only apply to the chemical, but may also be useful to assess an individual's metabolic properties. In addition, it is demonstrated that the greater part of erythrocytes and benzidine-hemoglobin adducts are eliminated randomly in rats, i.e., following first-order kinetics.

  10. Polycyclic Aromatic Hydrocarbon (PAH Exposure and DNA Adduct Semi-Quantitation in Archived Human Tissues

    Directory of Open Access Journals (Sweden)

    M. Margaret Pratt

    2011-06-01

    Full Text Available Polycyclic aromatic hydrocarbons (PAHs are combustion products of organic materials, mixtures of which contain multiple known and probable human carcinogens. PAHs occur in indoor and outdoor air, as well as in char-broiled meats and fish. Human exposure to PAHs occurs by inhalation, ingestion and topical absorption, and subsequently formed metabolites are either rendered hydrophilic and excreted, or bioactivated and bound to cellular macromolecules. The formation of PAH-DNA adducts (DNA binding products, considered a necessary step in PAH-initiated carcinogenesis, has been widely studied in experimental models and has been documented in human tissues. This review describes immunohistochemistry (IHC studies, which reveal localization of PAH-DNA adducts in human tissues, and semi-quantify PAH-DNA adduct levels using the Automated Cellular Imaging System (ACIS. These studies have shown that PAH-DNA adducts concentrate in: basal and supra-basal epithelium of the esophagus, cervix and vulva; glandular epithelium of the prostate; and cytotrophoblast cells and syncitiotrophoblast knots of the placenta. The IHC photomicrographs reveal the ubiquitous nature of PAH-DNA adduct formation in human tissues as well as PAH-DNA adduct accumulation in specific, vulnerable, cell types. This semi-quantative method for PAH-DNA adduct measurement could potentially see widespread use in molecular epidemiology studies.

  11. Detection and characterization of human serum antibodies to polycyclic aromatic hydrocarbon diol-epoxide DNA adducts

    Energy Technology Data Exchange (ETDEWEB)

    Newman, M.J.; Light, B.A.; Weston, A.; Tollurud, D.; Clark, J.L.; Mann, D.L.; Blackmon, J.P.; Harris, C.C.

    1988-07-01

    The presence of serum antibodies to the diol-epoxide DNA adducts of representative polycyclic aromatic hydrocarbons (PAH), chrysene, benz(a)anthracene and benzo(a)pyrene, was determined by ELISA using serum samples obtained from normal healthy individuals. Antibodies that reacted against PAH adducted-DNA, but not against PAH-adducted protein, were found in the serum of approximately 40% of the test individuals. Specificity analysis of the antibodies demonstrated that serological cross-reactions between the benzo(a)pyrene and the chrysene diol-epoxide adducts were present. Similar cross-reactivity between the benz(a)anthracene and the chrysene adducts was observed. Sera containing antibodies that were apparently specific for each of the three PAH-DNA adducts were also identified. The presence of antibodies to PAH-DNA adducts indicates both past exposure to these carcinogenic PAH and their metabolic activation to the DNA damaging metabolites. These antibodies may prove to be useful in both retrospective and prospective epidemiological studies of various diseases associated with PAH exposure.

  12. Reactivity of monofunctional cis-platinum adducts as a function of DNA sequence.

    Science.gov (United States)

    Malinge, J M; Leng, M

    1988-08-11

    The purpose of this work was to study the chemical reactivity of monofunctional cis-platinum-nucleic acid adducts as a function of nucleic acid sequence. The first part of the paper deals with the formation of these adducts. It is shown that the ternary nucleic acid-cis-platinum-ethidium bromide complexes in which ethidium bromide and nucleotide residues are cross-linked by cis-platinum, are relatively unstable at 37 degrees C. In the presence of acridine, ethidium bromide (but not cis-platinum) is slowly released which leads to the formation of monofunctional cis-platinum-nucleic acid adducts. After removal of acridine, the monofunctional adducts react further to become bifunctional. The second part of the paper deals with the kinetics of disappearance of the monofunctional adducts in several polynucleotides but not in poly(dG).poly(dC). When the adducts possess a chloride ligand, the limiting step in the cross-linking is the rate of aquation reaction of the chloride ligand. The rate constants are an order of magnitude larger when the monofunctional adducts do not possess a chloride ligand. In both the cases, the rate constants are apparently independent of the nucleic acid sequence.

  13. The role of cell hydration in realization of biological effects of non-ionizing radiation (NIR).

    Science.gov (United States)

    Ayrapetyan, Sinerik

    2015-09-01

    The weak knowledge on the nature of cellular and molecular mechanisms of biological effects of NIR such as static magnetic field, infrasound frequency of mechanical vibration, extremely low frequency of electromagnetic fields and microwave serves as a main barrier for adequate dosimetry from the point of Public Health. The difficulty lies in the fact that the biological effects of NIR depend not only on their thermodynamic characteristics but also on their frequency and intensity "windows", chemical and physical composition of the surrounding medium, as well as on the initial metabolic state of the organism. Therefore, only biomarker can be used for adequate estimation of biological effect of NIR on organisms. Because of the absence of such biomarker(s), organizations having the mission to monitor hazardous effects of NIR traditionally base their instruction on thermodynamic characteristics of NIR. Based on the high sensitivity to NIR of both aqua medium structure and cell hydration, it is suggested that cell bathing medium is one of the primary targets and cell hydration is a biomarker for NIR effects on cells and organisms. The purpose of this article is to present a short review of literature and our own experimental data on the effects of NIR on plants' seeds germination, microbe growth and development, snail neurons and heart muscle, rat's brain and heart tissues.

  14. Is ground cover vegetation an effective biological control enhancement strategy against olive pests?

    Directory of Open Access Journals (Sweden)

    Daniel Paredes

    Full Text Available Ground cover vegetation is often added or allowed to generate to promote conservation biological control, especially in perennial crops. Nevertheless, there is inconsistent evidence of its effectiveness, with studies reporting positive, nil or negative effects on pest control. This might arise from differences between studies at the local scale (e.g. orchard management and land use history, the landscape context (e.g. presence of patches of natural or semi-natural vegetation near the focal orchard, or regional factors, particularly climate in the year of the study. Here we present the findings from a long-term regional monitoring program conducted on four pest species (Bactrocera oleae, Prays oleae, Euphyllura olivina, Saissetia oleae in 2,528 olive groves in Andalusia (Spain from 2006 to 2012. Generalized linear mixed effect models were used to analyze the effect of ground cover on different response variables related to pest abundance, while accounting for variability at the local, landscape and regional scales. There were small and inconsistent effects of ground cover on the abundance of pests whilst local, landscape and regional variability explained a large proportion of the variability in pest response variables. This highlights the importance of local and landscape-related variables in biological control and the potential effects that might emerge from their interaction with practices, such as groundcover vegetation, implemented to promote natural enemy activity. The study points to perennial vegetation close to the focal crop as a promising alternative strategy for conservation biological control that should receive more attention.

  15. Is ground cover vegetation an effective biological control enhancement strategy against olive pests?

    Science.gov (United States)

    Paredes, Daniel; Cayuela, Luis; Gurr, Geoff M; Campos, Mercedes

    2015-01-01

    Ground cover vegetation is often added or allowed to generate to promote conservation biological control, especially in perennial crops. Nevertheless, there is inconsistent evidence of its effectiveness, with studies reporting positive, nil or negative effects on pest control. This might arise from differences between studies at the local scale (e.g. orchard management and land use history), the landscape context (e.g. presence of patches of natural or semi-natural vegetation near the focal orchard), or regional factors, particularly climate in the year of the study. Here we present the findings from a long-term regional monitoring program conducted on four pest species (Bactrocera oleae, Prays oleae, Euphyllura olivina, Saissetia oleae) in 2,528 olive groves in Andalusia (Spain) from 2006 to 2012. Generalized linear mixed effect models were used to analyze the effect of ground cover on different response variables related to pest abundance, while accounting for variability at the local, landscape and regional scales. There were small and inconsistent effects of ground cover on the abundance of pests whilst local, landscape and regional variability explained a large proportion of the variability in pest response variables. This highlights the importance of local and landscape-related variables in biological control and the potential effects that might emerge from their interaction with practices, such as groundcover vegetation, implemented to promote natural enemy activity. The study points to perennial vegetation close to the focal crop as a promising alternative strategy for conservation biological control that should receive more attention.

  16. Biological effects of atmospheric particles on human bronchial epithelial cells. Comparison with diesel exhaust particles.

    Science.gov (United States)

    Baulig, Augustin; Sourdeval, Matthieu; Meyer, Martine; Marano, Francelyne; Baeza-Squiban, Armelle

    2003-01-01

    Epidemiological studies have associated the increase of respiratory disorders with high levels of ambient particulate matter (PM) levels although the underlying biological mechanisms are unclear. PM are a complex mixture of particles with different origins but in urban areas, they mainly contain soots from transport like Diesel exhaust particles (DEP). In order to determine whether PM biological effects can be explained by the presence of DEP, the effects of urban PM, DEP and carbon black particles (CB) were compared on a human bronchial epithelial cell line (16-HBE14o-). Two types of PM were used : reference material (RPM) and PM with an aerodynamic diameter particles. However, DEP and to a lower extent PM inhibited cell proliferation, induced the release of a pro-inflammatory cytokine, GM-CSF, and generated a pro-oxidant state as shown by the increased intracellular peroxides production. By contrast, CB never induced such effects. Nevertheless CB are more endocytosed than DEP whereas PM are the less endocytosed particles. In conclusion, PM induced to a lower extent the same biological effects than DEP in 16-HBE cells suggesting that particle characteristics should be thoroughly considered in order to clearly correlate adverse effects of PM to their composition and to clarify the role of DEP in PM effects.

  17. Complex conformational heterogeneity of the highly flexible O6-benzyl-guanine DNA adduct.

    Science.gov (United States)

    Wilson, Katie A; Wetmore, Stacey D

    2014-07-21

    The conformational preference of the O6-benzyl-guanine (BzG) adduct was computationally examined using nucleoside, nucleotide, and DNA models, which provided critical information about the potential mutagenic consequences and toxicity of the BzG adduct in our cells. Substantial conformational flexibility of the BzG moiety, including rotation of the bulky group with respect to the base and the internal conformation of the bulk moiety, is seen in the nucleoside and nucleotide models. This large conformational flexibility suggests the conformation adopted by BzG is dependent on the local environment of the BzG adduct. Upon incorporation of the adduct into the DNA helix, the BzG conformational flexibility is maintained. The range of BzG conformations adopted in DNA likely arises due to a combination of the long and flexible (-CH2-) linker, the small adduct size, and the lack of discrete interactions between the bulky moiety and G. Because of the conformational flexibility of the adduct, many DNA conformations are observed for BzG adducted DNA, including those not previously reported in the literature, and thus, a modified nomenclature for adducted DNA conformations is presented. Furthermore, the preferred conformation of BzG adducted DNA is greatly dependent on a number of factors, including the pairing nucleotide, the discrete interactions in the helix, and the solvation of the benzyl moiety. These factors in turn lead to a complicated mutagenic and toxic profile that may invoke pairing with natural C, mispairs, or deletion mutations, which is supported by previously reported experimental biochemical studies. Despite this complex mutagenic profile, pairing with C leads to the most stable helical structure, which is the first combined structural and energetic explanation for experimental studies reporting a higher rate of C incorporation than any other nucleobase upon BzG replication.

  18. Benthic biological effects of seasonal hypoxia in a eutrophic estuary predate rapid coastal development

    Science.gov (United States)

    Bishop, Melanie J.; Powers, Sean P.; Porter, Hugh J.; Peterson, Charles H.

    2006-11-01

    Nutrient and organic loading associated with escalating human activities increases biological oxygen demand from microbial decomposition. In the Neuse River estuary, North Carolina, recurrent nuisance algal blooms, bottom-water hypoxic events, and fish kills during summers of the 1990s suggest that uncapped nutrient loading may have increased the frequency, duration, and/or spatial scope of important biological effects of hypoxia during summer, when persistent water column stratification can occur and microbial metabolism is greatest. We test the hypothesis that the severity of benthic biological effects of hypoxia in this estuary has increased over a 30-year period of dramatic human population growth in eastern North Carolina by comparing survival over summer of the benthic bivalve Macoma spp. between historical (1968-1970) and recent (1997-1998) years. Macoma is a demonstrated indicator of oxygen availability, the benthic biomass dominant in the Neuse and other temperate estuaries and the major prey link to higher trophic levels. All three historical summers exhibited patterns of collapse in Macoma populations indistinguishable from the recent summer of severe hypoxia (1997) but distinct from the modest changes documented during the mildly hypoxic summer of 1998. The only Macoma to survive any severely hypoxic summer were those in shallows where oxygen could be renewed by surface mixing. Thus, the biological effects of hypoxia observed in the Neuse River estuary in the late 1990s appear no more severe than 30 years before. Historic rates of organic loading to the Neuse River estuary may have been sufficient to induce widespread and intense hypoxia beneath the surface mixed layer, implying that even if algal blooms are diminished through nutrient reductions, the severity of biological effects of bottom-water hypoxia may not change detectably.

  19. Formation of pyrophosphate-like adducts from nerve agents sarin, soman and cyclosarin in phosphate buffer: implications for analytical and toxicological investigations.

    Science.gov (United States)

    Gäb, Jürgen; John, Harald; Blum, Marc-Michael

    2011-01-15

    Phosphate buffer is frequently used in biological, biochemical and biomedical applications especially when pH is to be controlled around the physiological value of 7.4. One of the prerequisites of a buffer compound among good buffering capacity and pH stability over time is its non-reactivity with other constituents of the solution. This is especially important for quantitative analytical or toxicological assays. Previous work has identified a number of amino alcohol buffers like TRIS to react with G-type nerve agents sarin, soman and cyclosarin to form stable phosphonic diesters. In case of phosphate buffer we were able to confirm not only the rapid hydrolysis of these agents to the respective alkyl methylphosphonates but also the formation of substantial amounts of pyrophosphate-like adducts (phosphorylated methylphosphonates), which very slowly hydrolyzed following zero-order kinetics. This led to a complex mixture of phosphorus containing species with changing concentrations over time. We identified the molecular structure of these buffer adducts using 1D ¹H-³¹P HSQC NMR and LC-ESI-MS/MS techniques. Reaction rates of adduct formation are fast enough to compete with hydrolysis in aqueous solution and to yield substantial amounts of buffer adduct over the course of just a couple of minutes. Possible reaction mechanisms are discussed with respect to the formation and subsequent hydrolysis of the pyrophosphate-like compounds as well as the increased rate of hydrolysis of the nerve agent to the corresponding alkyl methylphosphonates. In summary, the use of phosphate buffer for the development of new assays with sarin, soman and cyclosarin is discouraged. Already existing protocols should be carefully reexamined on an individual basis.

  20. Base-Displaced Intercalated Structure of the N-(2'-Deoxyguanosin-8-yl)-3-aminobenzanthrone DNA Adduct.

    Science.gov (United States)

    Politica, Dustin A; Malik, Chanchal K; Basu, Ashis K; Stone, Michael P

    2015-12-21

    3-Nitrobenzanthrone (3-NBA), an environmental mutagen found in diesel exhaust and a suspected carcinogen, undergoes metabolic reduction followed by reaction with DNA to form aminobenzanthrone (ABA) adducts, with the major alkylation product being N-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone (C8-dG-ABA). Site-specific synthesis of the C8-dG-ABA adduct in the oligodeoxynucleotide 5'-d(GTGCXTGTTTGT)-3':5'-d(ACAAACACGCAC)-3'; X = C8-dG-ABA adduct, including codons 272-275 of the p53 gene, has allowed for investigation into the structural and thermodynamic properties of this adduct. The conformation of the C8-dG-ABA adduct was determined using NMR spectroscopy and was refined using molecular dynamics (MD) calculations restrained by experimentally determined interproton distance restraints obtained from NOE experiments. The refined structure revealed that the C8-dG-ABA adduct formed a base-displaced intercalated conformation. The adducted guanine was shifted into the syn conformation about the glycosidic bond. The 5'- and 3'-neighboring base pairs remained intact. While this facilitated π-stacking interactions between the ABA moiety and neighboring bases, the thermal melting temperature (Tm) of the adduct-containing duplex showed a decrease of 11 °C as compared to the corresponding unmodified oligodeoxynucleotide duplex. Overall, in this sequence, the base-displaced intercalated conformation of the C8-dG-ABA lesion bears similarity to structures of other arylamine C8-dG adducts. However, in this sequence, the base-displaced intercalated conformation for the C8-dG-ABA adduct differs from the conformation of the N(2)-dG-ABA adduct reported by de los Santos and co-workers, in which it is oriented in the minor groove toward the 5' end of the duplex, with the modified guanine remaining in the anti conformation about the glyosidic torsion angle, and the complementary base remaining within the duplex. The results are discussed in relationship to differences between the C8-d

  1. 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.

  2. Distinct biological effects of different nanoparticles commonly used in cosmetics and medicine coatings

    Directory of Open Access Journals (Sweden)

    Yu Julia X

    2011-05-01

    Full Text Available Abstract Background Metal oxides in nanoparticle form such as zinc oxide and titanium dioxide now appear on the ingredient lists of household products as common and diverse as cosmetics, sunscreens, toothpaste, and medicine. Previous studies of zinc oxide and titanium dioxide in non-nanoparticle format using animals have found few adverse effects. This has led the FDA to classify zinc oxide as GRAS (generally recognized as safe for use as a food additive. However, there is no regulation specific for the use of these chemicals in nanoparticle format. Recent studies, however, have begun to raise concerns over the pervasive use of these compounds in nanoparticle forms. Unfortunately, there is a lack of easily-adaptable screening methods that would allow for the detection of their biological effects. Results We adapted two image-based assays, a fluorescence resonance energy transfer-based caspase activation assay and a green fluorescent protein coupled-LC3 assay, to test for the biological effects of different nanoparticles in a high-throughput format. We show that zinc oxide nanoparticles are cytotoxic. We also show that titanium dioxide nanoparticles are highly effective in inducing autophagy, a cellular disposal mechanism that is often activated when the cell is under stress. Conclusion We suggest that these image-based assays provide a method of screening for the biological effects of similar compounds that is both efficient and sensitive as well as do not involve the use of animals.

  3. In vitro cultured cells as probes for space radiation effects on biological systems

    Energy Technology Data Exchange (ETDEWEB)

    Meli, A.; Perrella, G.; Curcio, F.; Ambesi-Impiombato, F.S. [Dipartimento di Patologia e Medicina Sperimentale e Clinica, Universita di Udine, P.le S. Maria della Misericordia, 33100 Udine (Italy)

    1999-12-06

    Near future scenarios of long-term and far-reaching manned space missions, require more extensive knowledge of all possible biological consequences of space radiation, particularly in humans, on both a long-term and a short-term basis. In vitro cultured cells have significantly contributed to the tremendous advancement of biomedical research. It is therefore to be expected that simple biological systems such as cultured cells, will contribute to space biomedical sciences. Space represents a novel environment, to which life has not been previously exposed. Both microgravity and space radiation are the two relevant components of such an environment, but biological adaptive mechanisms and efficient countermeasures can significantly minimize microgravity effects. On the other hand, it is felt that space radiation risks may be more relevant and that defensive strategies can only stem from our deeper knowledge of biological effects and of cellular repair mechanisms. Cultured cells may play a key role in such studies. Particularly, thyroid cells may be relevant because of the exquisite sensitivity of the thyroid gland to radiation. In addition, a clone of differentiated, normal thyroid follicular cells (FRTL5 cells) is available in culture, which is well characterized and particularly fit for space research.

  4. Biological Effect of Ultraviolet Photocatalysis on Nanoscale Titanium with a Focus on Physicochemical Mechanism.

    Science.gov (United States)

    Wu, Jingyi; Zhou, Lei; Ding, Xianglong; Gao, Yan; Liu, Xiangning

    2015-09-15

    Physicochemical properties, regulated by various surface modifications, influence the biological performance of materials. The interaction between surface charge and biomolecules is key to understanding the mechanism of surface-tissue integration. The objective of this study was to evaluate the biological response to a nanoscale titanium surface after ultraviolet (UVC, λ = 250 ± 20 nm) irradiation and to analyze the effects via a physicochemical mechanism. The surface characteristics were evaluated by field-emission scanning electron microscopy, X-ray photoelectron spectroscopy, surface profilometry, and contact angle assay. In addition, we applied the zeta-potential, a direct method to measure the electrostatic charge on UV-treated and UV-untreated titanium nanotube surfaces. The effect of the Ti surface after UV treatment on the biological process was determined by analyzing bovine serum albumin (BSA) adsorption and osteoblast-like MG-63 early adhesion, morphology, cytoskeletal arrangement, proliferation, and focal adhesion. Compared to an anodized titanium nanotube coating, UV irradiation altered the contact angles on the control surface from 51.5° to 6.2° without changing the surface topography or roughness. Furthermore, titanium nanotubes after UV treatment showed a significant reduction in the content of acidic hydroxyl groups and held less negative charge than the anodized coating. With regard to the biological response, along with an enhanced capability to adsorb BSA, osteoblasts exhibited higher colonization and viability on the UV-treated material. The results suggest that UV treatment enhances the biocompatibility by reducing the electrostatic repulsion between biomaterials and biomolecules.

  5. Constraining the sensitivity of iodide adduct chemical ionization mass spectrometry to multifunctional organic molecules using the collision limit and thermodynamic stability of iodide ion adducts

    Science.gov (United States)

    Lopez-Hilfiker, Felipe D.; Iyer, Siddarth; Mohr, Claudia; Lee, Ben H.; D'Ambro, Emma L.; Kurtén, Theo; Thornton, Joel A.

    2016-04-01

    The sensitivity of a chemical ionization mass spectrometer (ions formed per number density of analytes) is fundamentally limited by the collision frequency between reagent ions and analytes, known as the collision limit, the ion-molecule reaction time, and the transmission efficiency of product ions to the detector. We use the response of a time-of-flight chemical ionization mass spectrometer (ToF-CIMS) to N2O5, known to react with iodide at the collision limit, to constrain the combined effects of ion-molecule reaction time, which is strongly influenced by mixing and ion losses in the ion-molecule reaction drift tube. A mass spectrometric voltage scanning procedure elucidates the relative binding energies of the ion adducts, which influence the transmission efficiency of molecular ions through the electric fields within the vacuum chamber. Together, this information provides a critical constraint on the sensitivity of a ToF-CIMS towards a wide suite of routinely detected multifunctional organic molecules for which no calibration standards exist. We describe the scanning procedure and collision limit determination, and we show results from the application of these constraints to the measurement of organic aerosol composition at two different field locations.

  6. Effectiveness of biological surrogates for predicting patterns of marine biodiversity: a global meta-analysis.

    Directory of Open Access Journals (Sweden)

    Camille Mellin

    Full Text Available The use of biological surrogates as proxies for biodiversity patterns is gaining popularity, particularly in marine systems where field surveys can be expensive and species richness high. Yet, uncertainty regarding their applicability remains because of inconsistency of definitions, a lack of standard methods for estimating effectiveness, and variable spatial scales considered. We present a Bayesian meta-analysis of the effectiveness of biological surrogates in marine ecosystems. Surrogate effectiveness was defined both as the proportion of surrogacy tests where predictions based on surrogates were better than random (i.e., low probability of making a Type I error; P and as the predictability of targets using surrogates (R(2. A total of 264 published surrogacy tests combined with prior probabilities elicited from eight international experts demonstrated that the habitat, spatial scale, type of surrogate and statistical method used all influenced surrogate effectiveness, at least according to either P or R(2. The type of surrogate used (higher-taxa, cross-taxa or subset taxa was the best predictor of P, with the higher-taxa surrogates outperforming all others. The marine habitat was the best predictor of R(2, with particularly low predictability in tropical reefs. Surrogate effectiveness was greatest for higher-taxa surrogates at a <10-km spatial scale, in low-complexity marine habitats such as soft bottoms, and using multivariate-based methods. Comparisons with terrestrial studies in terms of the methods used to study surrogates revealed that marine applications still ignore some problems with several widely used statistical approaches to surrogacy. Our study provides a benchmark for the reliable use of biological surrogates in marine ecosystems, and highlights directions for future development of biological surrogates in predicting biodiversity.

  7. State-of-the-art exposure chamber for highly controlled and reproducible THz biological effects studies

    Science.gov (United States)

    Cerna, Cesario Z.; Elam, David P.; Echchgadda, Ibtissam; Sloan, Mark A.; Wilmink, Gerald J.

    2014-03-01

    Terahertz (THz) imaging and sensing technologies are increasingly being used at international airports for security screening purposes and at major medical centers for cancer and burn diagnosis. The emergence of new THz applications has directly resulted in an increased interest regarding the biological effects associated with this frequency range. Knowledge of THz biological effects is also desired for the safe use of THz systems, identification of health hazards, and development of empirically-based safety standards. In this study, we developed a state-of-the-art exposure chamber that allowed for highly controlled and reproducible studies of THz biological effects. This innovative system incorporated an industry grade cell incubator system that permitted a highly controlled exposure environment, where temperatures could be maintained at 37 °C +/- 0.1 °C, carbon dioxide (CO2) levels at 5% +/- 0.1%, and relative humidity (RH) levels at 95% +/- 1%. To maximize the THz power transmitted to the cell culture region inside the humid incubator, a secondary custom micro-chamber was fabricated and incorporated into the system. This micro-chamber shields the THz beam from the incubator environment and could be nitrogen-purged to eliminate water absorption effects. Additionally, a microscope that allowed for real-time visualization of the live cells before, during, and after THz exposure was integrated into the exposure system.

  8. The cost-effectiveness of biologics for the treatment of rheumatoid arthritis: a systematic review.

    Directory of Open Access Journals (Sweden)

    Jaana T Joensuu

    Full Text Available Economic evaluations provide information to aid the optimal utilization of limited healthcare resources. Costs of biologics for Rheumatoid arthritis (RA are remarkably high, which makes these agents an important target for economic evaluations. This systematic review aims to identify existing studies examining the cost-effectiveness of biologics for RA, assess their quality and report their results systematically.A literature search covering Medline, Scopus, Cochrane library, ACP Journal club and Web of Science was performed in March 2013. The cost-utility analyses (CUAs of one or more available biological drugs for the treatment of RA in adults were included. Two independent investigators systematically collected information and assessed the quality of the studies. To enable the comparison of the results, all costs were converted to 2013 euro.Of the 4890 references found in the literature search, 41 CUAs were included in the current systematic review. While considering only direct costs, the incremental cost-effectiveness ratio (ICER of the tumor necrosis factor inhibitors (TNFi ranged from 39,000 to 1,273,000 €/quality adjusted life year (QALY gained in comparison to conventional disease-modifying antirheumatic drugs (cDMARDs in cDMARD naïve patients. Among patients with an insufficient response to cDMARDs, biologics were associated with ICERs ranging from 12,000 to 708,000 €/QALY. Rituximab was found to be the most cost-effective alternative compared to other biologics among the patients with an insufficient response to TNFi.When 35,000 €/QALY is considered as a threshold for the ICER, TNFis do not seem to be cost-effective among cDMARD naïve patients and patients with an insufficient response to cDMARDs. With thresholds of 50,000 to 100,000 €/QALY biologics might be cost-effective among patients with an inadequate response to cDMARDs. Standardization of multiattribute utility instruments and a validated standard conversion method

  9. The Cost-Effectiveness of Biologics for the Treatment of Rheumatoid Arthritis: A Systematic Review

    Science.gov (United States)

    Joensuu, Jaana T.; Huoponen, Saara; Aaltonen, Kalle J.; Konttinen, Yrjö T.; Nordström, Dan; Blom, Marja

    2015-01-01

    Background and Objectives Economic evaluations provide information to aid the optimal utilization of limited healthcare resources. Costs of biologics for Rheumatoid arthritis (RA) are remarkably high, which makes these agents an important target for economic evaluations. This systematic review aims to identify existing studies examining the cost-effectiveness of biologics for RA, assess their quality and report their results systematically. Methods A literature search covering Medline, Scopus, Cochrane library, ACP Journal club and Web of Science was performed in March 2013. The cost-utility analyses (CUAs) of one or more available biological drugs for the treatment of RA in adults were included. Two independent investigators systematically collected information and assessed the quality of the studies. To enable the comparison of the results, all costs were converted to 2013 euro. Results Of the 4890 references found in the literature search, 41 CUAs were included in the current systematic review. While considering only direct costs, the incremental cost-effectiveness ratio (ICER) of the tumor necrosis factor inhibitors (TNFi) ranged from 39,000 to 1 273,000 €/quality adjusted life year (QALY) gained in comparison to conventional disease-modifying antirheumatic drugs (cDMARDs) in cDMARD naïve patients. Among patients with an insufficient response to cDMARDs, biologics were associated with ICERs ranging from 12,000 to 708,000 €/QALY. Rituximab was found to be the most cost-effective alternative compared to other biologics among the patients with an insufficient response to TNFi. Conclusions When 35,000 €/QALY is considered as a threshold for the ICER, TNFis do not seem to be cost-effective among cDMARD naïve patients and patients with an insufficient response to cDMARDs. With thresholds of 50,000 to 100,000 €/QALY biologics might be cost-effective among patients with an inadequate response to cDMARDs. Standardization of multiattribute utility instruments

  10. Base-Displaced Intercalated Conformation of the 2-Amino-3-methylimidazo[4,5-f]quinoline N(2)-dG DNA Adduct Positioned at the Nonreiterated G(1) in the NarI Restriction Site.

    Science.gov (United States)

    Stavros, Kallie M; Hawkins, Edward K; Rizzo, Carmelo J; Stone, Michael P

    2015-07-20

    The conformation of an N(2)-dG adduct arising from the heterocyclic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a potent food mutagen, was determined in 5'-d(C(1)T(2)C(3)X(4)G(5)C(6)G(7)C(8)C(9)A(10)T(11)C(12))-3':5'-d(G(13)A(14)T(15)G(16)G(17)C(18)G(19)C(20)C(21)G(22)A(23)G(24))-3'; X = N(2)-dG-IQ, in which the modified nucleotide X(4) corresponds to G(1) in the 5'-d(G(1)G(2)CG(3)CC)-3' NarI restriction endonuclease site. Circular dichroism (CD) revealed blue shifts relative to the unmodified duplex, consistent with adduct-induced twisting, and a hypochromic effect for the IQ absorbance in the near UV region. NMR revealed that the N(2)-dG-IQ adduct adopted a base-displaced intercalated conformation in which the modified guanine remained in the anti conformation about the glycosidic bond, the IQ moiety intercalated into the duplex, and the complementary base C(21) was displaced into the major groove. The processing of the N(2)-dG-IQ lesion by hpol η is sequence-dependent; when placed at the reiterated G(3) position, but not at the G(1) position, this lesion exhibits a propensity for frameshift replication [Choi, J. Y., et al. (2006) J. Biol. Chem., 281, 25297-25306]. The structure of the N(2)-dG-IQ adduct at the nonreiterated G(1) position was compared to that of the same adduct placed at the G(3) position [Stavros, K. M., et al. (2014) Nucleic Acids Res., 42, 3450-3463]. CD indicted minimal spectral differences between the G(1) vs G(3) N(2)-dG-IQ adducts. NMR indicated that the N(2)-dG-IQ adduct exhibited similar base-displaced intercalated conformations at both the G(1) and G(3) positions. This result differed as compared to the corresponding C8-dG-IQ adducts placed at the same positions. The C8-dG-IQ adduct adopted a minor groove conformation when placed at position G(1) but a base-displaced intercalated conformation when placed at position G(3) in the NarI sequence. The present studies suggest that differences in lesion bypass by hpol η may be

  11. Effect of some botanical materials on certain biological aspects of the house fly, Musca domestica L

    Directory of Open Access Journals (Sweden)

    Nabawy A. I. Elkattan, Khalafalla S. Ahmed, Saadya M. Elbermawy and Rabab

    2011-04-01

    Full Text Available The effects of Lantana camara (leaves, Pelargonium zonale (leaves, Cupressus macrocarpa (leaves, Cyperus rotundus (whole plant and Acacia nilotica (seeds powders on some biological aspects of house fly, M. domestica L. were tested. The effects of three lethal concentrations LC25, LC50 and LC75 on the larval duration, pupation percent, pupal weight, pupal duration, adult emergence percent, sex ratio, adult longevity, and fecundity were determined. The induced malformed larvae, pupae and adults were recorded and photographed. The powders of the five plants were found to have promising effects in controlling this insect.

  12. Effective diffusion coefficient of biological liquids in porous calcium phosphate coatings

    Science.gov (United States)

    Nazarenko, N. N.; Knyazeva, A. G.

    2016-11-01

    The study offers a method to estimate effective diffusion coefficients for transfer of biological liquids in porous materials. The method is based on the analysis of areas occupied by pores and solid materials on slice images. The possibility is shown for ascertaining a correlation between the effective coefficient and technological conditions because different structure and porosity are observed experimentally. The correlations of effective diffusion coefficients with the production voltage for different coating-base compositions, on which the coating was grown, have been built.

  13. Characterization of the angular memory effect of scattered light in biological tissues

    Science.gov (United States)

    Schott, Sam; Bertolotti, Jacopo; Léger, Jean-Francois; Bourdieu, Laurent; Gigan, Sylvain

    2015-05-01

    High resolution optical microscopy is essential in neuroscience but suffers from scattering in biological tissues. It therefore grants access to superficial layers only. Recently developed techniques use scattered photons for imaging by exploiting angular correlations in transmitted light and could potentially increase imaging depths. But those correlations (`angular memory effect') are of very short range and, in theory, only present behind and not inside scattering media. From measurements on neural tissues and complementary simulations, we find that strong forward scattering in biological tissues can enhance the memory effect range (and thus the possible field-of-view) by more than an order of magnitude compared to isotropic scattering for $\\sim$1\\,mm thick tissue layers.

  14. Characterization of the angular memory effect of scattered light in biological tissues

    CERN Document Server

    Schott, Sam; Léger, Jean-Francois; Bourdieu, Laurent; Gigan, Sylvain

    2015-01-01

    High resolution optical microscopy is essential in neuroscience but suffers from scattering in biological tissues. It therefore grants access to superficial layers only. Recently developed techniques use scattered photons for imaging by exploiting angular correlations in transmitted light and could potentially increase imaging depths. But those correlations (`angular memory effect') are of very short range and, in theory, only present behind and not inside scattering media. From measurements on neural tissues and complementary simulations, we find that strong forward scattering in biological tissues can enhance the memory effect range (and thus the possible field-of-view) by more than an order of magnitude compared to isotropic scattering for $\\sim$1\\,mm thick tissue layers.

  15. DNA adducts and cancer risk in prospective studies: a pooled analysis and a meta-analysis

    DEFF Research Database (Denmark)

    Veglia, Fabrizio; Loft, Steffen; Matullo, Giuseppe;

    2008-01-01

    Bulky DNA adducts are biomarkers of exposure to aromatic compounds and of the ability of the individual to metabolically activate carcinogens and to repair DNA damage. Their ability to predict cancer onset is uncertain. We have performed a pooled analysis of three prospective studies on cancer risk...... in which bulky DNA adducts have been measured in blood samples collected from healthy subjects (N = 1947; average follow-up 51-137 months). In addition, we have performed a meta-analysis by identifying all articles on the same subject published up to the end of 2006, including case-control studies....... In the pooled analysis, a weakly statistically significant increase in the risk of lung cancer was apparent (14% per unit standard deviation change in adduct levels, 95% confidence interval 1-28%; using the weighted mean difference method, 0.15 SD, units higher adducts in cases than in controls...

  16. Lifetimes and stabilities of familiar explosive molecular adduct complexes during ion mobility measurements.

    Science.gov (United States)

    McKenzie-Coe, Alan; DeBord, John Daniel; Ridgeway, Mark; Park, Melvin; Eiceman, Gary; Fernandez-Lima, Francisco

    2015-08-21

    Trapped ion mobility spectrometry coupled to mass spectrometry (TIMS-MS) was utilized for the separation and identification of familiar explosives in complex mixtures. For the first time, molecular adduct complex lifetimes, relative stability, binding energies and candidate structures are reported for familiar explosives. Experimental and theoretical results showed that the adduct size and reactivity, complex binding energy and the explosive structure tailor the stability of the molecular adduct complex. The flexibility of TIMS to adapt the mobility separation as a function of the molecular adduct complex stability (i.e., short or long IMS experiments/low or high IMS resolution) permits targeted measurements of explosives in complex mixtures with high confidence levels.

  17. NEW THIO S2- ADDUCTS WITH ANTIMONY (III AND V HALIDE: SYNTHESIS AND INFRARED STUDY

    Directory of Open Access Journals (Sweden)

    HASSAN ALLOUCH

    2013-12-01

    Full Text Available Five new S2- adducts with SbIII and SbV halides have been synthesized and studied by infrared. Discrete structures have been suggested, the environment around the antimony being tetrahedral, trigonal bipyramidal or octahedral.

  18. Recent progress in quantitative analysis of DNA adducts of nephrotoxin aristolochic acid

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Aristolochic acid (AA), a mixture of structure-related nitrophenanthrene carboxylic acid derivatives derived from Aristolochia spp, is associated with nephrotoxin and carcinogen. AA-DNA adducts induced by reductive metabolic activation of AA were detected in tissues of animals and in patients exposed to AA. The DNA adducts were generally used as biomarkers in toxicological study of AA. In this short review, quantitative analysis of AA-DNA adducts in various in vitro and in vivo systems by using 32P-postlabelling assay, HPLC-UV, HPLC-radiation monitor, HPLC-FLD, HPLC-ESI/MS and UPLC-MS/MS methods is discussed. The distribution of AA-DNA adducts in various tissues is also summarized.

  19. Effect of non-crop vegetation types on conservation biological control of pests in olive groves

    OpenAIRE

    2013-01-01

    Conservation biological control (CBC) is an environmentally sound potential alternative to the use of chemical insecticides. It involves modifications of the environment to promote natural enemy activity on pests. Despite many CBC studies increasing abundance of natural enemies, there are far fewer demonstrations of reduced pest density and very little work has been conducted in olive crops. In this study we investigated the effects of four forms of non-crop vegetation on the abundance of two...

  20. Cumulative and Synergistic Effects of Physical, Biological, and Acoustic Signals on Marine Mammal Habitat Use

    Science.gov (United States)

    2013-10-28

    seasonal breakup of the ice has begun. The bowhead whales detections finally disappear as these mammals begin their annual migration to the Arctic Ocean...Final Report Cumulative and Synergistic Effects of Physical, Biological, and Acoustic Signals on Marine Mammal Habitat Use Jeffrey A Nystuen...signals impact marine mammal habitat use. This is especially critical in areas like the Bering Sea where global climate change can lead to rapid changes

  1. Effects of organic amendment on soil quality as assessed by biological indicators

    OpenAIRE

    Sultana, Salma

    2011-01-01

    Soil quality decline is one of the most predominant effect deriving from human activities. In particular, intensive agricultural management can affect negatively soils, principally due to rapid depletion of soil organic matter, that affects, in turn, soil physical, chemical and biological properties. The declining trend of soil quality coupled with mismanagement of agricultural production is pose a serious threat to sustainability of intensive agriculture. Sustainable intensive agriculture is...

  2. Biological Effects of Short, High-Level Exposure to Gases: Nitrogen Oxides.

    Science.gov (United States)

    1980-07-01

    SUPPLEMENTARY NOT ES3 This project was one of four under the same contract; the others covered ammonia , carbon monoxide, and sulfur dioxide. 3 IS. KEY wOROS...characterize the biological responses to short, high-level exposures to four gases associated with certain Army weapons systems ( ammonia , carbon monoxide...20- i --- 7 (2) Biochemical and Other Effects Buckley and BalchumlO found biochemical changes, principally in enzyme activity of the liver, spleen

  3. Computation of the effective mechanical response of biological networks accounting for large configuration changes.

    Science.gov (United States)

    El Nady, K; Ganghoffer, J F

    2016-05-01

    The asymptotic homogenization technique is involved to derive the effective elastic response of biological membranes viewed as repetitive beam networks. Thereby, a systematic methodology is established, allowing the prediction of the overall mechanical properties of biological membranes in the nonlinear regime, reflecting the influence of the geometrical and mechanical micro-parameters of the network structure on the overall response of the equivalent continuum. Biomembranes networks are classified based on nodal connectivity, so that we analyze in this work 3, 4 and 6-connectivity networks, which are representative of most biological networks. The individual filaments of the network are described as undulated beams prone to entropic elasticity, with tensile moduli determined from their persistence length. The effective micropolar continuum evaluated as a continuum substitute of the biological network has a kinematics reflecting the discrete network deformation modes, involving a nodal displacement and a microrotation. The statics involves the classical Cauchy stress and internal moments encapsulated into couple stresses, which develop internal work in duality to microcurvatures reflecting local network undulations. The relative ratio of the characteristic bending length of the effective micropolar continuum to the unit cell size determines the relevant choice of the equivalent medium. In most cases, the Cauchy continuum is sufficient to model biomembranes. The peptidoglycan network may exhibit a re-entrant hexagonal configuration due to thermal or pressure fluctuations, for which micropolar effects become important. The homogenized responses are in good agreement with FE simulations performed over the whole network. The predictive nature of the employed homogenization technique allows the identification of a strain energy density of a hyperelastic model, for the purpose of performing structural calculations of the shape evolutions of biomembranes.

  4. [Properties and biological effect of dust of various artificial mineral fibers].

    Science.gov (United States)

    Elovskaja, L T; Werner, I; Kupina, L M; Loscilov, J A; Efremov, L D

    1990-09-01

    Developments and use of man-made mineral fibres are important for the progress in some technical fields. In the last years the number of man-made mineral fibres increased extraordinarily. For the medical evaluation it is necessary to determine the physico-chemical characteristics of the man-made mineral fibre dust and its biological effects in animal experiments. The results of the investigations are described.

  5. On the effect of prestrain and residual stress in thin biological membranes.

    Science.gov (United States)

    Rausch, Manuel K; Kuhl, Ellen

    2013-09-01

    Understanding the difference between ex vivo and in vivo measurements is critical to interpret the load carrying mechanisms of living biological systems. For the past four decades, the ex vivo stiffness of thin biological membranes has been characterized using uniaxial and biaxial tests with remarkably consistent stiffness parameters, even across different species. Recently, the in vivo stiffness was characterized using combined imaging techniques and inverse finite element analyses. Surprisingly, ex vivo and in vivo stiffness values differed by up to three orders of magnitude. Here, for the first time, we explain this tremendous discrepancy using the concept of prestrain. We illustrate the mathematical modeling of prestrain in nonlinear continuum mechanics through the multiplicative decomposition of the total elastic deformation into prestrain-induced and load-induced parts. Using in vivo measured membrane kinematics and associated pressure recordings, we perform an inverse finite element analysis for different prestrain levels and show that the resulting membrane stiffness may indeed differ by four orders of magnitude depending on the prestrain level. Our study motivates the hypothesis that prestrain is important to position thin biological membranes in vivo into their optimal operating range, right at the transition point of the stiffening regime. Understanding the effect of prestrain has direct clinical implications in regenerative medicine, medical device design, and and tissue engineering of replacement constructs for thin biological membranes.

  6. Effect of the flavonoid rutin on the biology of Spodoptera frugiperda (Lepidoptera: Noctuidae

    Directory of Open Access Journals (Sweden)

    Talita Roberta Ferreira Borges Silva

    2016-04-01

    Full Text Available The fall armyworm Spodoptera frugiperda (J.E. Smith (Lepidoptera: Noctuidae is a major pest of maize crops in Brazil. The effects of plant metabolites on the biology and behavior of insects is little studied. The aim of the study was to evaluate the activity of rutin on the biology of the S. frugiperda by using artificial diets containing rutin. The study evaluated four treatments: regular diet (control group and diets containing 1.0, 2.0 and 3.0 mg g-1 of rutin. The following biological variables parameters of the larvae were evaluated daily: development time (days, larval and pupal weight (g and viability (%, adult longevity and total life cycle (days. A completely randomized experimental design was used with 25 replication. The rutin flavonoid negatively affected the biology of S. frugiperda by prolonging the larval development time, reducing the weight of larvae and pupae and decreasing the viability of the pupae. The addition of different concentrations of rutin prolonged the S. frugiperda life cycle. The use of plant with insecticidal activity has the potential with strategy in IPM.

  7. Relative biological effectiveness for photons: implication of complex DNA double-strand breaks as critical lesions

    Science.gov (United States)

    Liang, Ying; Fu, Qibin; Wang, Xudong; Liu, Feng; Yang, Gen; Luo, Chunxiong; Ouyang, Qi; Wang, Yugang

    2017-03-01

    Current knowledge in radiobiology ascribes the adverse biological effects of ionizing radiation primarily to the induction of DNA double-strand breaks (DSBs), which is supposed to be potentially lethal and may be converted to lethal damage due to misrepair. Soft and ultrasoft x-rays have been found to bear elevated biological effectiveness for cell killing compared with conventional x-rays or 60Co γ-rays. This phenomenon is qualitatively interpreted as the increased level of DSB induction for low energy photons, however, a thorough quantitative reasoning is lacking. Here, we systematically compared the relative biological effectiveness (RBE) with relative DSB induction for photons from several hundreds of eV up to MeV. Although there is an approximate two-fold increase in the yields of DSB for low energy photons found in our calculation and a large number of experimental measurements, it is far from enough to account for the three- to four-fold increase in RBE. Further theoretical investigations show that DSB complexity (additional single-strand breaks and base damage within 10 base pairs) increases notably for low energy photons, which largely reconciles the discrepancy between RBE and DSB induction. Our theoretical results are in line with accumulating experimental evidence that complex DSBs are refractory to repair machinery and may contribute predominantly to the formation of lethal damage.

  8. Deciphering the biological effects of acupuncture treatment modulating multiple metabolism pathways.

    Science.gov (United States)

    Zhang, Aihua; Yan, Guangli; Sun, Hui; Cheng, Weiping; Meng, Xiangcai; Liu, Li; Xie, Ning; Wang, Xijun

    2016-02-16

    Acupuncture is an alternative therapy that is widely used to treat various diseases. However, detailed biological interpretation of the acupuncture stimulations is limited. We here used metabolomics and proteomics technology, thereby identifying the serum small molecular metabolites into the effect and mechanism pathways of standardized acupuncture treatments at 'Zusanli' acupoint which was the most often used acupoint in previous reports. Comprehensive overview of serum metabolic profiles during acupuncture stimulation was investigated. Thirty-four differential metabolites were identified in serum metabolome and associated with ten metabolism pathways. Importantly, we have found that high impact glycerophospholipid metabolism, fatty acid metabolism, ether lipid metabolism were acutely perturbed by acupuncture stimulation. As such, these alterations may be useful to clarify the biological mechanism of acupuncture stimulation. A series of differentially expressed proteins were identified and such effects of acupuncture stimulation were found to play a role in transport, enzymatic activity, signaling pathway or receptor interaction. Pathway analysis further revealed that most of these proteins were found to play a pivotal role in the regulation of multiple metabolism pathways. It demonstrated that the metabolomics coupled with proteomics as a powerful approach for potential applications in understanding the biological effects of acupuncture stimulation.

  9. Analysis of MIR-18 results for physical and biological dosimetry: radiation shielding effectiveness in LEO

    Science.gov (United States)

    Cucinotta, F. A.; Wilson, J. W.; Williams, J. R.; Dicello, J. F.

    2000-01-01

    We compare models of radiation transport and biological response to physical and biological dosimetry results from astronauts on the Mir space station. Transport models are shown to be in good agreement with physical measurements and indicate that the ratio of equivalent dose from the Galactic Cosmic Rays (GCR) to protons is about 3/2:1 and that this ratio will increase for exposures to internal organs. Two biological response models are used to compare to the Mir biodosimetry for chromosome aberration in lymphocyte cells; a track-structure model and the linear-quadratic model with linear energy transfer (LET) dependent weighting coefficients. These models are fit to in vitro data for aberration formation in human lymphocytes by photons and charged particles. Both models are found to be in reasonable agreement with data for aberrations in lymphocytes of Mir crew members: however there are differences between the use of LET dependent weighting factors and track structure models for assigning radiation quality factors. The major difference in the models is the increased effectiveness predicted by the track model for low charge and energy ions with LET near 10 keV/micrometers. The results of our calculations indicate that aluminum shielding, although providing important mitigation of the effects of trapped radiation, provides no protective effect from the galactic cosmic rays (GCR) in low-earth orbit (LEO) using either equivalent dose or the number of chromosome aberrations as a measure until about 100 g/cm 2 of material is used.

  10. Nanometallomics: an emerging field studying the biological effects of metal-related nanomaterials.

    Science.gov (United States)

    Li, Yu-Feng; Gao, Yuxi; Chai, Zhifang; Chen, Chunying

    2014-02-01

    Metallomics, focusing on the global and systematic understanding of the metal uptake, trafficking, role and excretion in biological systems, has attracted more and more attention. Metal-related nanomaterials, including metallic and metal-containing nanomaterials, have unique properties compared to their micro-scaled counterparts and therefore require special attention. The small size effect, surface effect, and quantum size effect directly influence the physicochemical properties of nanostructured materials and their fate and behavior in biota. However, to our knowledge, the metallomics itself did not touch this special category of materials yet. Therefore, the term "nanometallomics" is proposed and the systematic study on the absorption, distribution, metabolism, excretion (ADME) behavior of metal-related nanomaterials in biological systems and their interactions with genes, proteins and other biomolecules will be reviewed. The ADME behavior of metal-related nanomaterials in the biological systems is influenced by their physicochemical properties, the exposure route, and the microenvironment of the deposition site. Nanomaterials may not only interact directly or indirectly with genes, proteins and other molecules to cause DNA damage, genotoxicity, immunotoxicity, and cytotoxicity, but also stimulate the immune responses, circumvent tumor resistance and inhibit tumor metastasis. Nanometallomics needs to be integrated with other omics sciences, such as genomics, proteomics and metabolomics, to explore the biomedical data and obtain the overall knowledge of underlying mechanisms, and therefore to improve the application performance and to reduce the potential risk of metal-related nanomaterials.

  11. Halothane potentiates the alcohol-adduct induced TNF-alpha release in heart endothelial cells

    Directory of Open Access Journals (Sweden)

    Freeman Thomas L

    2005-04-01

    Full Text Available Abstract Background The possibility exists for major complications to occur when individuals are intoxicated with alcohol prior to anesthetization. Halothane is an anesthetic that can be metabolized by the liver into a highly reactive product, trifluoroacetyl chloride, which reacts with endogenous proteins to form a trifluoroacetyl-adduct (TFA-adduct. The MAA-adduct which is formed by acetaldehyde (AA and malondialdehyde reacting with endogenous proteins, has been found in both patients and animals chronically consuming alcohol. These TFA and MAA-adducts have been shown to cause the release of inflammatory products by various cell types. If both adducts share a similar mechanism of cell activation, receiving halothane anesthesia while intoxicated with alcohol could exacerbate the inflammatory response and lead to cardiovascular injury. Methods We have recently demonstrated that the MAA-adduct induces tumor necrosis factor-α (TNF-α release by heart endothelial cells (HECs. In this study, pair and alcohol-fed rats were randomized to receive halothane pretreatments intra peritoneal. Following the pretreatments, the intact heart was removed, HECs were isolated and stimulated with unmodified bovine serum albumin (Alb, MAA-modified Alb (MAA-Alb, Hexyl-MAA, or lipopolysaccharide (LPS, and supernatant concentrations of TNF-α were measured by ELISA. Results Halothane pre-treated rat HECs released significantly greater TNF-α concentration following MAA-adduct and LPS stimulation than the non-halothane pre-treated in both pair and alcohol-fed rats, but was significantly greater in the alcohol-fed rats. Conclusion These results demonstrate that halothane and MAA-adduct pre-treatment increases the inflammatory response (TNF-α release. Also, these results suggest that halothane exposure may increase the risk of alcohol-induced heart injury, since halothane pre-treatment potentiates the HEC TNF-α release measured following both MAA-Alb and LPS

  12. Translesion synthesis past acrolein-derived DNA adducts by human mitochondrial DNA polymerase γ.

    Science.gov (United States)

    Kasiviswanathan, Rajesh; Minko, Irina G; Lloyd, R Stephen; Copeland, William C

    2013-05-17

    Acrolein, a mutagenic aldehyde, is produced endogenously by lipid peroxidation and exogenously by combustion of organic materials, including tobacco products. Acrolein reacts with DNA bases forming exocyclic DNA adducts, such as γ-hydroxy-1,N(2)-propano-2'-deoxyguanosine (γ-HOPdG) and γ-hydroxy-1,N(6)-propano-2'-deoxyadenosine (γ-HOPdA). The bulky γ-HOPdG adduct blocks DNA synthesis by replicative polymerases but can be bypassed by translesion synthesis polymerases in the nucleus. Although acrolein-induced adducts are likely to be formed and persist in mitochondrial DNA, animal cell mitochondria lack specialized translesion DNA synthesis polymerases to tolerate these lesions. Thus, it is important to understand how pol γ, the sole mitochondrial DNA polymerase in human cells, acts on acrolein-adducted DNA. To address this question, we investigated the ability of pol γ to bypass the minor groove γ-HOPdG and major groove γ-HOPdA adducts using single nucleotide incorporation and primer extension analyses. The efficiency of pol γ-catalyzed bypass of γ-HOPdG was low, and surprisingly, pol γ preferred to incorporate purine nucleotides opposite the adduct. Pol γ also exhibited ∼2-fold lower rates of excision of the misincorporated purine nucleotides opposite γ-HOPdG compared with the corresponding nucleotides opposite dG. Extension of primers from the termini opposite γ-HOPdG was accomplished only following error-prone purine nucleotide incorporation. However, pol γ preferentially incorporated dT opposite the γ-HOPdA adduct and efficiently extended primers from the correctly paired terminus, indicating that γ-HOPdA is probably nonmutagenic. In summary, our data suggest that acrolein-induced exocyclic DNA lesions can be bypassed by mitochondrial DNA polymerase but, in the case of the minor groove γ-HOPdG adduct, at the cost of unprecedented high mutation rates.

  13. Structural Elucidation of a Carnosine-Acrolein Adduct and its Quantification in Human Urine Samples.

    Science.gov (United States)

    Bispo, Vanderson S; de Arruda Campos, Ivan P; Di Mascio, Paolo; Medeiros, Marisa H G

    2016-01-19

    Aldehydes accumulate in inflammation, during myocardial infarction and have been associated with pain symptoms. One pathway of aldehyde detoxification is the conjugation with carnosine. A 3-methylpyridinium carnosine adduct from the reaction of carnosine and acrolein was characterized using extensive spectroscopic measurements. The adduct with urinary concentrations of 1.82 ± 0.68 nmol/mg of creatinine is one of the most abundant acrolein metabolites in urine and opens promising therapeutic strategies for carnosine.

  14. DNA adducts in human tissues:biomarkers of exposure to carcinogens in tobacco smoke

    OpenAIRE

    Phillips, D.H.

    1996-01-01

    Tobacco smoking causes millions of cancer deaths annually. Tobacco smoke is a complex mixture of thousands of chemicals including many known animal carcinogens. Because many carcinogens from DNA adducts in target animal or human tissues, the detection of the formation of adducts using such methods as postlabeling, immunoassay, fluorescence spectroscopy, and mass spectrometry is a means of monitoring human exposure to tobacco carcinogens. Smokers are at increased risk of cancer in many organs,...

  15. New insight into the molecular mechanisms of the biological effects of DNA minor groove binders.

    Directory of Open Access Journals (Sweden)

    Xinbo Zhang

    Full Text Available BACKGROUND: Bisbenzimides, or Hoechst 33258 (H258, and its derivative Hoechst 33342 (H342 are archetypal molecules for designing minor groove binders, and widely used as tools for staining DNA and analyzing side population cells. They are supravital DNA minor groove binders with AT selectivity. H342 and H258 share similar biological effects based on the similarity of their chemical structures, but also have their unique biological effects. For example, H342, but not H258, is a potent apoptotic inducer and both H342 and H258 can induce transgene overexpression in in vitro studies. However, the molecular mechanisms by which Hoechst dyes induce apoptosis and enhance transgene overexpression are unclear. METHODOLOGY/PRINCIPAL FINDINGS: To determine the molecular mechanisms underlying different biological effects between H342 and H258, microarray technique coupled with bioinformatics analyses and multiple other techniques has been utilized to detect differential global gene expression profiles, Hoechst dye-specific gene expression signatures, and changes in cell morphology and levels of apoptosis-associated proteins in malignant mesothelioma cells. H342-induced apoptosis occurs in a dose-dependent fashion and is associated with morphological changes, caspase-3 activation, cytochrome c mitochondrial translocation, and cleavage of apoptosis-associated proteins. The antagonistic effect of H258 on H342-induced apoptosis indicates a pharmacokinetic basis for the two dyes' different biological effects. Differential global gene expression profiles induced by H258 and H342 are accompanied by unique gene expression signatures determined by DNA microarray and bioinformatics software, indicating a genetic basis for their different biological effects. CONCLUSIONS/SIGNIFICANCE: A unique gene expression signature associated with H342-induced apoptosis provides a new avenue to predict and classify the therapeutic class of minor groove binders in the drug

  16. Novel Biological Approaches for Testing the Contributions of Single DSBs and DSB Clusters to the Biological Effects of High LET Radiation.

    Science.gov (United States)

    Mladenova, Veronika; Mladenov, Emil; Iliakis, George

    2016-01-01

    The adverse biological effects of ionizing radiation (IR) are commonly attributed to the generation of DNA double-strand breaks (DSBs). IR-induced DSBs are generated by clusters of ionizations, bear damaged terminal nucleotides, and frequently comprise base damages and single-strand breaks in the vicinity generating a unique DNA damage-clustering effect that increases DSB "complexity." The number of ionizations in clusters of different radiation modalities increases with increasing linear energy transfer (LET), and is thought to determine the long-known LET-dependence of the relative biological effectiveness (RBE). Multiple ionizations may also lead to the formation of DSB clusters, comprising two or more DSBs that destabilize chromatin further and compromise overall processing. DSB complexity and DSB-cluster formation are increasingly considered in the development of mathematical models of radiation action, which are then "tested" by fitting available experimental data. Despite a plethora of such mathematical models the ultimate goal, i.e., the "a priori" prediction of the radiation effect, has not yet been achieved. The difficulty partly arises from unsurmountable difficulties in testing the fundamental assumptions of such mathematical models in defined biological model systems capable of providing conclusive answers. Recently, revolutionary advances in methods allowing the generation of enzymatic DSBs at random or in well-defined locations in the genome, generate unique testing opportunities for several key assumptions frequently fed into mathematical modeling - including the role of DSB clusters in the overall effect. Here, we review the problematic of DSB-cluster formation in radiation action and present novel biological technologies that promise to revolutionize the way we address the biological consequences of such lesions. We describe new ways of exploiting the I-SceI endonuclease to generate DSB-clusters at random locations in the genome and describe the

  17. How does airway exposure of aflatoxin B1 affect serum albumin adduct concentrations? Evidence based on epidemiological study and animal experimentation.

    Science.gov (United States)

    Mo, Xianwei; Lai, Hao; Yang, Yang; Xiao, Jun; He, Ke; Liu, Chao; Chen, Jiansi; Lin, Yuan

    2014-08-01

    levels of AFB1 in their serum with a minimum effective dose of 0.05 mg/kg/day; while 11 of 17 (64.71%) rabbits had detectable levels of AFB1 albumin adducts in the high exposure group (0.075 mg/kg/day), and only 5 rabbits (26.32%) had detectable levels of AFB1 albumin adducts in the moderate exposure group (0.05 mg/kg/day). No rabbits had detectable levels of AFB1 albumin adducts in the low exposure group (0.025 mg/kg/day). Our results demonstrated that only exposure to a certain level of AFB1 would result in detectable levels of serum AFB1 albumin adducts. Interventional programs aimed at reducing exposure to AFB1 by inhalation are urgently needed in high-risk populations. Additional large-sample, well-designed randomized controlled trials are needed to further confirm our results.

  18. Estimativa da entalpia reticular de adutos (DM Hm o utilizando-se formas modificadas da equação de Kapustinskii Estimating the value of lattice enthalpy (DM Hm o for adducts by using modified forms of Kapustinskii equation

    Directory of Open Access Journals (Sweden)

    Robson Fernandes de Farias

    1999-04-01

    Full Text Available In this work are presented two modified forms of Kapustinskii equation that could be used to estimate the values of the lattice enthalphies for adducts: DM Hm o=(-n.z+ .z- .10(2/D.(1-d*/D .K and DM Hm o=(-n.z+ .z-.10(2/d.(1-d*/d.K.d. Two new parameters related with steric effects and donor power of the ligands, J anddare introduced. The proposed equations were tested for 49 adducts (mainly from the zinc group halides. The difference between experimental (calorimetric and calculated values (using the proposed equations values are less than 5% for 41 of the tested adducts.

  19. Biomonitoring Human Albumin Adducts: The Past, the Present, and the Future

    Science.gov (United States)

    2016-01-01

    Serum albumin (Alb) is the most abundant protein in blood plasma. Alb reacts with many carcinogens and/or their electrophilic metabolites. Studies conducted over 20 years ago showed that Alb forms adducts with the human carcinogens aflatoxin B1 and benzene, which were successfully used as biomarkers in molecular epidemiology studies designed to address the role of these chemicals in cancer risk. Alb forms adducts with many therapeutic drugs or their reactive metabolites such as β-lactam antibiotics, acetylsalicylic acid, acetaminophen, nonsteroidal anti-inflammatory drugs, chemotherapeutic agents, and antiretroviral therapy drugs. The identification and characterization of the adduct structures formed with Alb have served to understand the generation of reactive metabolites and to predict idiosyncratic drug reactions and toxicities. The reaction of candidate drugs with Alb is now exploited as part of the battery of screening tools to assess the potential toxicities of drugs. The use of gas chromatography-mass spectrometry, liquid chromatography, or liquid chromatography-mass spectrometry (LC-MS) enabled the identification and quantification of multiple types of Alb xenobiotic adducts in animals and humans during the past three decades. In this perspective, we highlight the history of Alb as a target protein for adduction to environmental and dietary genotoxicants, pesticides, and herbicides, common classes of medicinal drugs, and endogenous electrophiles, and the emerging analytical mass spectrometry technologies to identify Alb-toxicant adducts in humans. PMID:27989119

  20. Specific incorporation of an artificial nucleotide opposite a mutagenic DNA adduct by a DNA polymerase.

    Science.gov (United States)

    Wyss, Laura A; Nilforoushan, Arman; Eichenseher, Fritz; Suter, Ursina; Blatter, Nina; Marx, Andreas; Sturla, Shana J

    2015-01-14

    The ability to detect DNA modification sites at single base resolution could significantly advance studies regarding DNA adduct levels, which are extremely difficult to determine. Artificial nucleotides that are specifically incorporated opposite a modified DNA site offer a potential strategy for detection of such sites by DNA polymerase-based systems. Here we investigate the action of newly synthesized base-modified benzimidazole-derived 2'-deoxynucleoside-5'-O-triphosphates on DNA polymerases when performing translesion DNA synthesis past the pro-mutagenic DNA adduct O(6)-benzylguanine (O(6)-BnG). We found that a mutated form of KlenTaq DNA polymerase, i.e., KTqM747K, catalyzed O(6)-BnG adduct-specific processing of the artificial BenziTP in favor of the natural dNTPs. Steady-state kinetic parameters revealed that KTqM747K catalysis of BenziTP is 25-fold more efficient for template O(6)-BnG than G, and 5-fold more efficient than natural dTMP misincorporation in adduct bypass. Furthermore, the nucleotide analogue BenziTP is required for full-length product formation in O(6)-BnG bypass, as without BenziTP the polymerase stalls at the adduct site. By combining the KTqM747K polymerase and BenziTP, a first round of DNA synthesis enabled subsequent amplification of Benzi-containing DNA. These results advance the development of technologies for detecting DNA adducts.