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Sample records for ultimate carcinogenic metabolite

  1. Electrophoretic mobility of PM2 DNA treated with ultimate chemical carcinogens or with ultraviolet light

    International Nuclear Information System (INIS)

    Thielmann, H.W.; Hecht, R.

    1980-01-01

    Superhelical DNA of the Pseudomonas phage PM2 was irradiated with UV-light or reacted with covalently binding carcinogens, such as 7-bromomethyl-benz[a]anthracene, (Ac) 2 ONFln, K-region epoxides, and alkylating agents. Migration velocity of the DNA products was determined using agarose gel electrophoresis. In gels of more than 1.3%-1.9% agarose, modified PM2 DNA exhibited a dose-(concentration-)dependent decrease of migration velocity. This phenomenon is probably due to a decrease in superhelix density which caused the compact DNA coil to assume eventually an open-circular conformation. Comparison of the extent of DNA modification with the decrease of migration velocity revealed that the superhelical structure sensitively reflected the chemical DNA alterations. DNA species exhibiting in 1.6% agarose gels, a migration velocity of up to 30% of that of control DNA showed an increase of velocity in 0.4% agarose. Therefore, in 1.3%-1.9% agarose gels, the decrease of superhelix density is accompanied by an increase of the frictional coefficient, whereas in 0.4%-0.9% agarose gels the same decrease of superhelix density apparently led to a higher degree of flexibility of the macromolecule and/or exposure of additional electric charges. (orig.) [de

  2. 7-Glutathione-pyrrole and 7-cysteine-pyrrole are potential carcinogenic metabolites of pyrrolizidine alkaloids.

    Science.gov (United States)

    He, Xiaobo; Xia, Qingsu; Fu, Peter P

    2017-04-03

    Many pyrrolizidine alkaloids (PAs) are hepatotoxic, genotoxic, and carcinogenic phytochemicals. Metabolism of PAs in vivo generates four (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-DNA adducts that have been proposed to be responsible for PA-induced liver tumor formation in rats. In this present study, we determined that the same set of DHP-DNA adducts was formed upon the incubation of 7-glutathione-DHP and 7-cysteine-DHP with cultured human hepatocarcinoma HepG2 cells. These results suggest that 7-glutathione-DHP and 7-cysteine-DHP are reactive metabolites of PAs that can bind to cellular DNA to form DHP-DNA adducts in HepG2 cells, and can potentially initiate liver tumor formation.

  3. Metabolism and excretion of 1-hydroxymethylpyrene, the proximate metabolite of the carcinogen 1-methylpyrene, in rats

    International Nuclear Information System (INIS)

    Bendadani, Carolin; Steinhauser, Lisa; Albert, Klaus; Glatt, Hansruedi; Monien, Bernhard H.

    2016-01-01

    1-Methylpyrene, an alkylated polycyclic aromatic hydrocarbon and environmental carcinogen, is activated by side-chain hydroxylation to 1-hydroxymethylpyrene (1-HMP) and subsequent sulfo conjugation to the DNA-reactive 1-sulfooxymethylpyrene. In addition to the bioactivation, processes of metabolic detoxification and transport greatly influence the genotoxicity of 1-methylpyrene. For a better understanding of 1-HMP detoxification in vivo we studied urinary and fecal metabolites in rats following intraperitoneal doses of 19.3 mg 1-HMP/kg body weight (5 rats) or the same dose containing 200 μCi [ 14 C]1-HMP/kg body weight (2 rats). After 48 h, 48.0% (rat 1) and 29.1% (rat 2) of the radioactivity was recovered as 1-HMP in the feces. Six major metabolites were observed by UV and on-line radioactivity detection in urine samples and feces after HPLC separation. The compounds were characterized by mass spectrometry, 1 H NMR and 1 H- 1 H COSY NMR spectroscopy, which allowed assigning tentative molecular structures. Two prominent metabolites, 1-pyrene carboxylic acid (M-6) and the acyl glucuronide of 1-pyrene carboxylic acid (M-5) accounted for 17.7% (rat 1) and 25.2% (rat 2) of the overall radioactive dose. Further, we detected the acyl glucuronide of 6-hydroxy-1-pyrene carboxylic acid (M-1) and 8-sulfooxy-1-pyrene carboxylic acid (M-3) together with two regioisomers of M-3 (M-2 and M-4) differing in position of the sulfate group at the pyrene ring. In urine samples, the radioactivity of 1-pyrene carboxylic acid and its five derivatives amounted to 32.4% (rat 1) or 45.5% (rat 2) of the total [ 14 C]1-HMP dose.

  4. Collision induced dissociation of protonated N-nitrosodimethylamine by ion trap mass spectrometry: Ultimate carcinogens in gas phase

    Science.gov (United States)

    Kulikova, Natalia; Baker, Michael; Gabryelski, Wojciech

    2009-12-01

    Collision induced dissociation of protonated N-nitrosodimethylamine (NDMA) and isotopically labeled N-nitrosodimethyl-d6-amine (NDMA-d6) was investigated by sequential ion trap mass spectrometry to establish mechanisms of gas phase reactions leading to intriguing products of this potent carcinogen. The fragmentation of (NDMA + H+) occurs via two dissociation pathways. In the alkylation pathway, homolytic cleavage of the N-O bond of N-dimethyl, N'-hydroxydiazenium ion generates N-dimethyldiazenium distonic ion which reacts further by a CH3 radical loss to form methanediazonium ion. Both methanediazonium ion and its precursor are involved in ion/molecule reactions. Methanediazonium ion showed to be capable of methylating water and methanol molecules in the gas phase of the ion trap and N-dimethyldiazenium distonic ion showed to abstract a hydrogen atom from a solvent molecule. In the denitrosation pathway, a tautomerization of N-dimethyl, N'-hydroxydiazenium ion to N-nitrosodimethylammonium intermediate ion results in radical cleavage of the N-N bond of the intermediate ion to form N-dimethylaminium radical cation which reacts further through [alpha]-cleavage to generate N-methylmethylenimmonium ion. Although the reactions of NDMA in the gas phase are different to those for enzymatic conversion of NDMA in biological systems, each activation method generates the same products. We will show that collision induced dissociation of N-nitrosodiethylamine (NDEA) and N-nitrosodipropylamine (NDPA) is also a feasible approach to gain information on formation, stability, and reactivity of alkylating agents originating from NDEA and NDPA. Investigating such biologically relevant, but highly reactive intermediates in the condensed phase is hampered by the short life-times of these transient species.

  5. Structure, function and carcinogenicity of metabolites of methylated and non-methylated polycyclic aromatic hydrocarbons: a comprehensive review.

    Science.gov (United States)

    Flesher, James W; Lehner, Andreas F

    2016-01-01

    The Unified Theory of PAH Carcinogenicity accommodates the activities of methylated and non-methylated polycyclic aromatic hydrocarbons (PAHs) and states that substitution of methyl groups on meso-methyl substituted PAHs with hydroxy, acetoxy, chloride, bromide or sulfuric acid ester groups imparts potent cancer producing properties. It incorporates specific predictions from past researchers on the mechanism of carcinogenesis by methyl-substituted hydrocarbons, including (1) requirement for metabolism to an ArCH2X type structure where X is a good leaving group and (2) biological substitution of a meso-methyl group at the most reactive center in non-methylated hydrocarbons. The Theory incorporates strong inferences of Fieser: (1) The mechanism of carcinogenesis involves a specific metabolic substitution of a hydrocarbon at its most reactive center and (2) Metabolic elimination of a carcinogen is a detoxifying process competitive with that of carcinogenesis and occurring by a different mechanism. According to this outlook, chemical or biochemical substitution of a methyl group at the reactive meso-position of non-methylated hydrocarbons is the first step in the mechanism of carcinogenesis for most, if not all, PAHs and the most potent metabolites of PAHs are to be found among the meso methyl-substituted hydrocarbons. Some PAHs and their known or potential metabolites and closely related compounds have been tested in rats for production of sarcomas at the site of subcutaneous injection and the results strongly support the specific predictions of the Unified Theory.

  6. A hydroxylated flavonol, fisetin inhibits the formation of a carcinogenic estrogen metabolite.

    Science.gov (United States)

    Meng, Xin; Sun, Hui; Yang, Lianrong; Yin, Rui; Qi, Lehui

    2017-03-01

    Fisetin can be found in a wide variety of plants and possesses strong efficacy against many cancers. 17β-Estradiol (E2) is hydrolyzed to 4-hydroxy-E2 (4-OHE2) via cytochrome P450 (CYP) 1B1 in vivo. In estrogen target tissues including the mammary gland, ovaries, and uterus, CYP1B1 is highly expressed, and 4-OHE2 is predominantly formed in cancerous tissues. Herein, we investigated the inhibitory activity of fisetin and flavone against CYP1B1 using estrogen E2 as substrate in vitro to reveal structure-activity relationship between structure of flavonoids and inhibition. The results showed that fisetin possessed inhibitory effect on CYP1B1 activity. Compared with flavone, the inhibition of fisetin was stronger. The V max and K i values were 1.950±0.157pmol/μgprotein/min and 4.925±0.689nM for fisetin and 2.277±0.231pmol/μgprotein/min and 9.148±2.150nM for flavone, respectively. By kinetic analyses, both fisetin and flavone displayed mixed inhibition. Taken together the data suggested that fisetin is able to inhibit the formation of carcinogenic 4-OHE2 from E2, which reveals one of its anti-cancer mechanisms and helps to reveal the relationship between the structure of flavonoids and the inhibition CYP1B1 for discovering new drugs in cancer therapy and prevention. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Identification of hepatic metabolites of two highly carcinogenic polycyclic aza-aromatic compounds, 7,9-dimethylbenz[c]acridine and 7,10-dimethylbenz[c]acridine.

    Science.gov (United States)

    Ye, Y; Duke, C C; Holder, G M

    1995-03-01

    The hepatic microsomal metabolites of the highly carcinogenic dimethylbenzacridines, 7,9-dimethylbenz[c]acridine (7,9-DMBAC), and 7,10-dimethylbenz[c]acridine (7,10-DMBAC) were obtained with preparations from 3-methylcholanthrene-pretreated rats. Metabolites were separated by reversed-phase HPLC and characterized using UV spectral data and chemical ionization-mass spectrometry after trimethylsilylation and GC. Comparisons with products formed in the presence of the epoxide hydrolase inhibitor, 1,1,1-trichloropropane 2,3-oxide and with those formed from the three synthetic alcohol derivatives of each parent compound, aided the assignment of firm or tentative structures to 16 products from 7,9-DMBAC found in 22 reversed-phase chromatographic peaks, and for 17 products of 7,10-DMBAC found in 19 chromatographic peaks. The more abundant metabolites were derived from oxidation of the methyl groups. Other metabolites were dihydrodiols, epoxides, phenols and secondary metabolites. The 9-methyl group prevented dihydrodiol formation at the 8,9-position from 7,9-DMBAC, and for each carcinogen, the 3,4-dihydrodiol was formed. As well, 3,4-dihydrodiols of methyl oxidized compounds were found.

  8. The hepatic metabolism of two carcinogenic dimethylbenz[c]acridines in control and induced rats: the distribution and the mutagenicity of metabolites.

    Science.gov (United States)

    Ye, Y; Scharping, C E; Holder, G M

    1995-04-01

    The major and minor metabolites of the potent polycyclic aza-aromatic carcinogens 7,9-dimethylbenz[c]acridine and 7,10-dimethylbenz[c]acridine, and the stereochemistry of the dihydrodiol metabolites have been previously described. The metabolite distributions produced in incubations of the aza-aromatic compounds with liver microsomes from phenobarbital- and 3-methylcholanthrene-pretreated and untreated rats, and the mutagenicity in the Ames test are described in this paper. The major metabolites of each were the alcohols produced by oxidation of the methyl group on the 8,9,10,11-ring for control and phenobarbital-induced preparations, while with 3-methylcholanthrene-induced preparations both the 7- and 9- (or 10-) monoalcohols were formed. Total monofunctionalized dihydrodiol metabolites, the 5,6- and 3,4-isomers for 7,9-dimethylbenz[c]acridine, and the 3,4-, 5,6- and 8,9-isomers for 7,10-dimethylbenz[c]acridine, constituted approximately 10% of total metabolites. As well, the K-region arene oxide was formed in substantial amounts with both compounds, accompanied in the case of 7,10-dimethylbenz[c]acridine with some 8,9-oxide. When incubations were carried out in the presence of the epoxide hydrase inhibitor 3,3,3-trichloropropane-1,2-oxide, dihydrodiol formation was almost completely inhibited and relative amounts of both phenols and oxides increased. Secondary metabolites were also formed to approximately 10% of the total products. The mutagenicity of synthetic alcohols and isolated purified metabolites was determined in the Salmonella mammalian microsome plate assay (Ames test) with strain TA100. Limited amounts of metabolites isolated precluded extensive testing, but high mutagenicities were noted for all 3,4-dihydrodiol derivatives isolated. These exceeded those of the parent aza-aromatic hydrocarbons. Alcohols were also active but less so than the parent compounds. The activation of these two dimethylbenz[c]acridines to mutagens appears to be through bay

  9. Ultimate pH values and bacteriological condition of meat and stress metabolites in blood of transported reindeer bulls

    Directory of Open Access Journals (Sweden)

    E. Wiklund

    2001-03-01

    Full Text Available Twenty-three reindeer bulls, aged 2-3 years, fed during two winter months at the Vuolda reindeer research station in Arjeplog, Sweden, were used in the study. The first group of eight reindeer was moved from their feeding corral to a selection corral, captured by lasso and stunned with a captive bolt outside the selection corral. The second group of seven reindeer was moved to the selection corral, captured by lasso and restrained, after which they were loaded onto a lorry- and transported for 1 hour and then slaughtered. The third group of eight reindeer was moved to the selection corral and herded directly onto the lorry, without any manual handling. They were transported for 5 h and then slaughtered. In both transport groups, four reindeer were fitted with pre-programmed automatic blood sampling equipment (ABSE. ABSE sampled blood at predetermined times via a jugular vein catheter. Ultimate pH-values in three muscles (Mm. longissimus, triceps brachii and biceps femoris were significantly lower in the group carefully handled and transported for 5 h compared with the other two groups. The physiological mechanisms behind these results are discussed. Samples from M. semimembranosus were collected at slaughter and after 2, 6 and 10 days of refrigerated storage (+4 °C. The samples were analysed for total counts of aerobic bacteria (pour-plated in Tryptone Glucose Extract Agar, Difco, incubated at 20 °C and 30 °C, respectively for 72 h, coliform bacteria 37 °C (pour-plated in Violet Red Bile Agar, Oxoid, incubated at 37 °C for 24 h, Enterococci (surface-plated onto Slantez and Bartley Agar, Oxoid, incubated at 44 °C for 48 h and Bacillus cereus (surface-plated onto Blood Agar Plates (Blood Agar Base, Difco, supplemented with 5% defibrinated horse blood 30 °C for 24 h. All samples fell in the range 'fit for consumption'. At slaughter, there was no difference in ASAT activity, urea and Cortisol concentrations between the two transported groups

  10. Sensory meat quality, ultimate pH values, blood metabolites and carcass parametersin reindeer (Rangifer tarandus tarandus L. fed various diets

    Directory of Open Access Journals (Sweden)

    Eva Wiklund

    2000-03-01

    Full Text Available This investigation was made to study and compare the effects of different diets on sensory meat quality and ultimate pH values in reindeer muscles and to relate stress-induced blood metabolites and carcass parameters to the meat quality traits measured. Altogether 23 female reindeer calves were included in the study. During an adaptation period, all reindeer were allowed free access to a mimicked natural diet containing 80% lichens (lichen diet. On January 28, 8 reindeer (group Cjan were slaughtered. Five reindeer (group C.Mar were allowed continuous free access to the lichen diet throughout the experiment. During 8 days, the other reindeer (groups PL and PS were given the lichen diet, half of the amount offered to the control group, and were then starved for one day. Thereafter, these reindeer were fed 80% commercial reindeer feed (pellets and either 20% lichens (group PL, or 20% silage (group PS for 5 weeks. After this, all animals were slaughtered. The average carcass weight and dressing percentage in the group fed commercial reindeer feed and lichens (PL were higher than in group CMar- Fat registrations were generally higher in groups PL and PS than in the groups Cj2n and CMar- Ultimate pH values in M. triceps brachii and M. longissimus were significantly lower in the group CMST than in PL. The levels of all blood metabolites (urea, ASAT and Cortisol were generally higher in groups PL and PS than in groups Cja„ and CMEF- NO significant differences were found in any of sensory attributes of the meat (monitored according to ISO standards. The present study shows that muscle and fat depots in reindeer can be improved by feeding a diet based on reindeer pellets but suggests that a feeding period of 35 days might be too short to affect the sensory properties of reindeer meat.

  11. Reproduction impact of mancozeb on rainbow trout (Oncorhynchus mykiss W. and accumulation of its carcinogen metabolite, ethylene thiourea in fish products

    Directory of Open Access Journals (Sweden)

    Milena TZANOVA

    2017-06-01

    Full Text Available Pesticides can be taken up from the water and accumulated in tissues of hydrobionts, often becoming multiplied thousands of times higher in the organism than in the surrounding water. The dithiocarbamate mancozeb is applied in plant protection as fungicide. In recent years the amount of mancozeb used in Europe significantly increased. It is carcinogen due to its metabolite - ethylene thiourea (ETU, which causes thyroid and pituitary tumors. The purpose of this study is to determinate the quantity of ethylene thiourea in products of rainbow trout (Oncorhynchus mykiss W., reared in environment containing permissible, according to the European law, amount of mancozeb. Seeking an answer to the question: is this concentration limit really safe for the reproduction of rainbow trout and can the more toxic metabolite - ETU, be accumulated in the fish eggs and fillet and afterwards make them harmful to the consumers? The study included 3 stages: feeding, analysis of ethylene thiourea in fish eggs and fillet by a new developed and validated HPLC (high performance liquid chromatography method and study of the reproductive indicators. The assays of ETU in all analyzed samples (fish and water were below the limit of quantification of the method, 0.05 mg*l-1, so fish do not accumulate the carcinogen degradation product of mancozeb and the maximum residue level of mancozeb is really safe for the humans as consumers. But these environmental conditions caused reproductive disorders. They can be partly compensated by using sperm activation medium for artificial insemination of trout eggs, but successful fertilization does not guarantee successful hatching, especially of eggs in trout farms with presence of mancozeb in water, even in allowable concentration. The presented results confirm previous investigation, that Salmonidae are very sensitive fish species, react to the lowest deviations in concentration levels of xenobiotics and are used for indicator of non

  12. Deconjugation of N-glucuronide conjugated metabolites with hydrazine hydrate - Biomarkers for exposure to the food-borne carcinogen 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)

    DEFF Research Database (Denmark)

    Frandsen, Henrik Lauritz

    2007-01-01

    The metabolism of the carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) has been investigated in rabbit liver S9. Two phase I metabolites, N-2-OH-PhIP and 4'-OH-PhIP were identified based on UV and mass spectra and co-elution with reference standards. Fortification of the incubation...

  13. Human cytochrome-P450 enzymes metabolize N-(2-methoxyphenyl)hydroxylamine, a metabolite of the carcinogens o-anisidine and o-nitroanisole, thereby dictating its genotoxicity.

    Science.gov (United States)

    Naiman, Karel; Martínková, Markéta; Schmeiser, Heinz H; Frei, Eva; Stiborová, Marie

    2011-12-24

    N-(2-Methoxyphenyl)hydroxylamine is a component in the human metabolism of two industrial and environmental pollutants and bladder carcinogens, viz. 2-methoxyaniline (o-anisidine) and 2-methoxynitrobenzene (o-nitroanisole), and it is responsible for their genotoxicity. Besides its capability to form three deoxyguanosine adducts in DNA, N-(2-methoxyphenyl)-hydroxylamine is also further metabolized by hepatic microsomal enzymes. To investigate its metabolism by human hepatic microsomes and to identify the major microsomal enzymes involved in this process are the aims of this study. N-(2-Methoxyphenyl)hydroxylamine is metabolized by human hepatic microsomes predominantly to o-anisidine, one of the parent carcinogens from which N-(2-methoxyphenyl)hydroxylamine is formed, while o-aminophenol and two N-(2-methoxyphenyl)hydroxylamine metabolites, whose exact structures have not been identified as yet, are minor products. Selective inhibitors of microsomal CYPs, NADPH:CYP reductase and NADH:cytochrome-b(5) reductase were used to characterize human liver microsomal enzymes reducing N-(2-methoxyphenyl)hydroxylamine to o-anisidine. Based on these studies, we attribute the main activity for this metabolic step in human liver to CYP3A4, 2E1 and 2C (more than 90%). The enzymes CYP2D6 and 2A6 also partake in this N-(2-methoxyphenyl)hydroxylamine metabolism in human liver, but only to ∼6%. Among the human recombinant CYP enzymes tested in this study, human CYP2E1, followed by CYP3A4, 1A2, 2B6 and 2D6, were the most efficient enzymes metabolizing N-(2-methoxyphenyl)hydroxylamine to o-anisidine. The results found in this study indicate that genotoxicity of N-(2-methoxyphenyl)hydroxylamine is dictated by its spontaneous decomposition to nitrenium/carbenium ions generating DNA adducts, and by its susceptibility to metabolism by CYP enzymes. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Expression profile of human cells in culture exposed to glycidamide, a reactive metabolite of the heat-induced food carcinogen acrylamide

    International Nuclear Information System (INIS)

    Clement, Flurina C.; Dip, Ramiro; Naegeli, Hanspeter

    2007-01-01

    Recent findings of acrylamide in many common foods have sparked renewed interest in assessing human health hazards and the long-term risk associated with exposure to vinyl compounds. Acrylamide is tumorigenic at high doses in rodents and has been classified as a probable human carcinogen. However, cancer risk projections in the population remain problematic because the molecular pathogenesis of acrylamide at the low level of dietary uptake is not understood. In particular, the question of whether specific transcriptional responses may amplify or mitigate the known genotoxicity of acrylamide has never been examined. Here, we used high-density DNA microarrays and PCR validations to assess genome-wide messenger profiles induced by glycidamide, the more reactive metabolite of acrylamide. The expression changes resulting from glycidamide treatment of human epithelial cells are characterized by the induction of detoxification enzymes, several members of the glutathione system and antioxidant factors. Low-dose experiments indicate that the up-regulation of epoxide hydrolase 1 represents the most sensitive transcriptional biomarker of glycidamide exposure. At higher concentrations, glycidamide induces typical markers of tumor progression such as steroid hormone activators, positive regulators of nuclear factor-κB, growth stimulators and apoptosis inhibitors. Concomitantly, growth suppressors and cell adhesion molecules are down-regulated. The main implication of these findings for risk assessment is that low concentrations of glycidamide elicit cytoprotective reactions whereas transcriptional signatures associated with tumor progression may be expected only at doses that exceed the range of ordinary dietary exposures

  15. The environmental carcinogen 3-nitrobenzanthrone and its main metabolite 3-aminobenzanthrone enhance formation of reactive oxygen intermediates in human A549 lung epithelial cells

    International Nuclear Information System (INIS)

    Hansen, Tanja; Seidel, Albrecht; Borlak, Juergen

    2007-01-01

    The environmental contaminant 3-nitrobenzanthrone (3-NBA) is highly mutagenic and a suspected human carcinogen. We aimed to evaluate whether 3-NBA is able to deregulate critical steps in cell cycle control and apoptosis in human lung epithelial A549 cells. Increased intracellular Ca 2+ and caspase activities were detected upon 3-NBA exposure. As shown by cell cycle analysis, an increased number of S-phase cells was observed after 24 h of treatment with 3-NBA. Furthermore, 3-NBA was shown to inhibit cell proliferation when added to subconfluent cell cultures. The main metabolite of 3-NBA, 3-ABA, induced statistically significant increases in tail moment as judged by alkaline comet assay. The potential of 3-NBA and 3-ABA to enhance the production of reactive oxygen species (ROS) was demonstrated by flow cytometry using 2',7'-dichlorofluorescein-diacetate (DCFH-DA). The enzyme inhibitors allopurinol, dicumarol, resveratrol and SKF525A were used to assess the impact of metabolic conversion on 3-NBA-mediated ROS production. Resveratrol decreased dichlorofluorescein (DCF) fluorescence by 50%, suggesting a role for CYP1A1 in 3-NBA-mediated ROS production. Mitochondrial ROS production was significantly attenuated (20% reduction) by addition of rotenone (complex I inhibition) and thenoyltrifluoroacetone (TTFA, complex II inhibition). Taken together, the results of the present study provide evidence for a genotoxic potential of 3-ABA in human epithelial lung cells. Moreover, both compounds lead to increased intracellular ROS and create an environment favorable to DNA damage and the promotion of cancer

  16. Human Microdosing with Carcinogenic Polycyclic Aromatic Hydrocarbons: In Vivo Pharmacokinetics of Dibenzo[ def,p ]chrysene and Metabolites by UPLC Accelerator Mass Spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Madeen, Erin P.; Ognibene, Ted J.; Corley, Richard A.; McQuistan, Tammie J.; Henderson, Marilyn C.; Baird, William M.; Bench, Graham; Turteltaub, Ken W.; Williams, David E.

    2016-10-17

    Metabolism is a key health risk factor following exposures to pro-carcinogenic polycyclic aromatic hydrocarbons (PAHs) such as dibenzo[def,p]chrysene (DBC), an IARC classified 2A probable human carcinogen. Human exposure to PAHs occurs primarily from the diet in non-smokers. However, little data is available on the metabolism and pharmacokinetics in humans of high molecular weight PAHs (≥4 aromatic rings), including DBC. We previously determined the pharmacokinetics of DBC in human volunteers orally administered a micro-dose (29 ng; 5 nCi) of [14C]-DBC by accelerator mass spectrometry (AMS) analysis of total [14C] in plasma and urine. In the current study, we utilized a novel “moving wire” interface between ultra-performance liquid chromatography (UPLC) and AMS to detect and quantify parent DBC and its major metabolites. The major [14C] product identified in plasma was unmetabolized [14C]-DBC itself, (Cmax= 18.5 ± 15.9 fg/mL, Tmax= 2.1 ± 1.0 h), whereas the major metabolite was identified as [14C]-(+/-)-DBC-11,12-diol (Cmax= 2.5 ± 1.3 fg/mL, Tmax= 1.8 h). Several minor species of [14C]-DBC metabolites were also detected for which no reference standards were available. Free and conjugated metabolites were detected in urine with [14C]-(+/-)-DBC-11,12,13,14-tetraol isomers identified as the major metabolites, 56.3% of which were conjugated (Cmax= 35.8 ± 23.0 pg/pool, Tmax= 6-12 h pool). [14C]-DBC-11,12-diol, of which 97.5% was conjugated, was also identified in urine (Cmax= 29.4 ± 11.6 pg/pool, Tmax= 6-12 h pool). Parent [14C]-DBC was not detected in urine. This is the first dataset to assess metabolite profiles and associated pharmacokinetics of a carcinogenic PAH in human volunteers at an environmentally relevant dose, providing the data necessary for translation of high dose animal models to humans for translation of environmental health risk assessment.

  17. The metabolic activation and nucleic acid adducts of naturally-occurring carcinogens: recent results with ethyl carbamate and the spice flavors safrole and estragole

    Energy Technology Data Exchange (ETDEWEB)

    Miller, J A; Miller, E C

    1983-07-01

    A small (approximately 30) but varied group of organic and inorganic compounds appear to be carcinogenic in both humans and experimental animals. A much larger number and wider variety of chemical carcinogens, primarily synthetic organic compounds, are known for experimental animals. These agents include a small (approximately 30) and varied group of metabolites of green plants and fungi. Many more of these carcinogens must exist in the living world. As with the synthetic carcinogens, the majority of these naturally occurring carcinogens are procarcinogens that require metabolic conversion into reactive electrophilic and mutagenic ultimate carcinogens. These strong electrophiles combine covalently and non-enzymatically with nucleophilic sites in DNAs, RNAs, proteins, and small molecules in target tissues. One or more of the DNA adducts appear to initiate carcinogenesis in an irreversible manner. The subsequent promotion step leading to gross tumours may be completed by further administration of carcinogen or by treatment with non-carcinogenic promoters. Roles for the RNA and protein adducts in the carcinogenic process have not been excluded. Recent data on the metabolic activation and reactivity in vivo of the naturally occurring carcinogens ethyl carbamate and certain of the alkenylbenzene spice flavours are illustrative of these principles. These agents can initiate the carcinogenic process in male mouse liver with small doses given prior to weaning. Subsequent growth of the liver and male hormonal factors appear to function as promoters leading to gross hepatic tumors after one year. Reactive electrophilic metabolites of ethyl carbamate and of safrole and estragole and their nucleic acid adducts formed during initiation in mouse liver have been characterized.

  18. Blood proteins as carcinogen dosimeters

    International Nuclear Information System (INIS)

    Tannenbaum, S.R.; Skipper, P.L.

    1986-01-01

    The problem of quantifying exposure to genotoxins in a given individual represents a formidable challenge. In this paper methods which rely on the covalent binding of carcinogens and their metabolites to blood proteins are described. That carcinogens interact with proteins as well as with DNA has been established, although whether protein-carcinogen adducts can result in genetic damage has not been established. It has been shown, however, that the amount of a protein carcinogen adduct formed may be used as a quantitative measure of exposure to a carcinogen. Such a measure presumably is reflective of the absorption, metabolism, and excretion of the compound in an exposed individual. Protein adduction may reflect exposure in a time-frame of weeks to months. Thus, protein adduct measurement is a form of human chemical dosimetry. Hemoglobin and albumin are promising candidates for such dosimeters. Hemoglobin has a lifetime of about 120 days in humans; thus, circulating levels of carcinogen-modified hemoglobin will reflect the level of carcinogen exposure during a period of nearly four months. It also possesses some metabolic competence, particularly, the ability to oxidize aromatic hydroxylamines to nitroso compounds which react quite efficiently with sulfhydryl groups. Albumin has a half-life of 20 to 25 days in man. This protein does not possess metabolic capacity other than, perhaps, some esterase activity. In contrast to hemoglobin, though, it is not protected by the erythrocyte membrane and might be the target for a greater number of carcinogens. It is present and is synthesized in the same cells in which the reactive metabolic intermediates of carcinogens are mostly formed - the hepatocytes. Also, albumin has a number of high-affinity binding sites for a broad spectrum of xenobiotics and endobiotics. 25 refs., 1 tab

  19. Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

    International Nuclear Information System (INIS)

    Kakehashi, Anna; Wei, Min; Fukushima, Shoji; Wanibuchi, Hideki

    2013-01-01

    This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P 450 inducers, such as phenobarbital, α-benzene hexachloride and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate

  20. Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Kakehashi, Anna; Wei, Min [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-Ku, Osaka 545-8585 (Japan); Fukushima, Shoji [Japan Bioassay Research Center, Japan Industrial Safety and Health Association, 2445 Hirasawa, Hadano, Kanagawa 257-0015 (Japan); Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-Ku, Osaka 545-8585 (Japan)

    2013-10-28

    This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P{sub 450} inducers, such as phenobarbital, α-benzene hexachloride and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate.

  1. Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

    Directory of Open Access Journals (Sweden)

    Hideki Wanibuchi

    2013-10-01

    Full Text Available This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P450 inducers, such as phenobarbital, a-benzene hexachloride and 1,1-bis(p-chlorophenyl-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate.

  2. Carcinogen derived biomarkers: applications in studies of human exposure to secondhand tobacco smoke

    OpenAIRE

    Hecht, S

    2004-01-01

    Objective: To review the literature on carcinogen derived biomarkers of exposure to secondhand tobacco smoke (SHS). These biomarkers are specifically related to known carcinogens in tobacco smoke and include urinary metabolites, DNA adducts, and blood protein adducts.

  3. Flux scaling: Ultimate regime

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Flux scaling: Ultimate regime. With the Nusselt number and the mixing length scales, we get the Nusselt number and Reynolds number (w'd/ν) scalings: and or. and. scaling expected to occur at extremely high Ra Rayleigh-Benard convection. Get the ultimate regime ...

  4. Stalking the ultimate particle

    CERN Multimedia

    2003-01-01

    If you missed the ARTE programme entitled "L'Ultime Particule" broadcast in February, you have another chance to catch it in CERN's Main Auditorium on 13 March. "L'Ultime Particule" is a documentary by the French director Michel Andrieu that seeks to explain particle physics through a contemplative quest for the research physicists of matter of today and yesteryear. Invariably kitted out in a red parka and a soft hat, the programme's investigator scours the planet and the archives in search of the research physicists who are stalking the ultimate particle, the Higgs boson, in their quest to understand the structure of matter. Naturally enough, CERN is an important stage of his journey where Michel Andrieu and his team spent several days last year. Both from the physics and metaphysical points of view, "L'Ultime Particule" is worth seeing. The film's director, Michel Andrieu, will introduce his documentary and answer questions from the audience after the documentary has been shown. L'Ultime Particule by Mic...

  5. The ultimate quotable Einstein

    CERN Document Server

    2011-01-01

    Here is the definitive new edition of the hugely popular collection of Einstein quotations that has sold tens of thousands of copies worldwide and been translated into twenty-five languages. The Ultimate Quotable Einstein features 400 additional quotes, bringing the total to roughly 1,600 in all. This ultimate edition includes new sections--"On and to Children," "On Race and Prejudice," and "Einstein's Verses: A Small Selection"--as well as a chronology of Einstein's life and accomplishments, Freeman Dyson's authoritative foreword, and new commentary by Alice Calaprice.

  6. Carcinogenicity and mutagenicity of chromium.

    Science.gov (United States)

    Léonard, A; Lauwerys, R R

    1980-11-01

    Occupational exposure represents the main source of human contamination by chromium. For non-occupationally exposed people the major environmental exposure to chromium occurs as a consequence of its presence in food. Chromium must be considered as an essential element. Its deficiency impairs glucose metabolism. Trivalent chromium salts are poorly absorbed through the gastro-intestinal and respiratory tracts because they do not cross membranes easily. Hexavalent chromium can be absorbed by the oral and pulmonary routes and probably also through the skin. After its absorption, hexavalent chromium is rapidly reduced to the trivalent form which is probably the only form to be found in biological material. Epidemiological studies have shown that some chromium salts (mainly the slightly soluble hexavalent salts) are carcinogens. Lung cancers have, indeed, often been reported among workers in chromate-producing industry and, to a lesser extent, in workers from the chrome-pigment industry. The first attempts to produce cancers in experimental animals by inhalation or parenteral introduction gave negative or equivocal results but, from 1960, positive results have been obtained with various chromium compounds. As for the carcinogenic activity, the mutagenicity of chromium has mainly been found with hexavalent salts. In the majority of assay systems used, trivalent chromium appears inactive. It can be considered as evident, however, that the ultimate mutagen which binds to the genetic material is the trivalent form produced intracellularly from hexavalent chromium, the apparent lack of activity of the trivalent form being due to its poor cellular uptake.

  7. The Ultimate Technology

    DEFF Research Database (Denmark)

    Riis, Søren

    2013-01-01

    One of the most influential philosophers of the 20th century, Martin Heidegger (1889-1976), died prior to the remarkable cloning of the sheep Dolly and before Dr. Venter started his experiments on creating synthetic life, and he never explicitly discussed living technologies. However, by reinterp......One of the most influential philosophers of the 20th century, Martin Heidegger (1889-1976), died prior to the remarkable cloning of the sheep Dolly and before Dr. Venter started his experiments on creating synthetic life, and he never explicitly discussed living technologies. However......, by reinterpreting his notion of "modern technology," this article shows how it is possible to philosophically assess living technologies and to recognize ways in which Heidegger anticipated this phenomenon with his notion of cybernetics. The interpretation elucidates the fundamental process of technology becoming...... living and simultaneously presents living technology as the ultimate technology. The thesis of this article is that living technology is not just one more technology; rather, it is the perfection of technology as understood by Aristotle. Aristotle's thinking is in this way a key example of a profound...

  8. Carcinogenic compounds in alcoholic beverages: an update.

    Science.gov (United States)

    Pflaum, Tabea; Hausler, Thomas; Baumung, Claudia; Ackermann, Svenja; Kuballa, Thomas; Rehm, Jürgen; Lachenmeier, Dirk W

    2016-10-01

    The consumption of alcoholic beverages has been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC) since 1988. More recently, in 2010, ethanol as the major constituent of alcoholic beverages and its metabolite acetaldehyde were also classified as carcinogenic to humans. Alcoholic beverages as multi-component mixtures may additionally contain further known or suspected human carcinogens as constituent or contaminant. This review will discuss the occurrence and toxicology of eighteen carcinogenic compounds (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, glyphosate, lead, 3-MCPD, 4-methylimidazole, N-nitrosodimethylamine, pulegone, ochratoxin A, safrole) occurring in alcoholic beverages as identified based on monograph reviews by the IARC. For most of the compounds of alcoholic beverages, quantitative risk assessment provided evidence for only a very low risk (such as margins of exposure above 10,000). The highest risk was found for ethanol, which may reach exposures in ranges known to increase the cancer risk even at moderate drinking (margin of exposure around 1). Other constituents that could pose a risk to the drinker were inorganic lead, arsenic, acetaldehyde, cadmium and ethyl carbamate, for most of which mitigation by good manufacturing practices is possible. Nevertheless, due to the major effect of ethanol, the cancer burden due to alcohol consumption can only be reduced by reducing alcohol consumption in general or by lowering the alcoholic strength of beverages.

  9. Dietary Carcinogens and Anticarcinogens.

    Science.gov (United States)

    Ames, Bruce N.

    1983-01-01

    Describes 16 mutagens/carcinogens found in plant food and coffee as well as several anticarcinogens also found in such food. Speculates on relevant biochemical mechanisms, particularly the role of oxygen radicals and their inhibitors in the fat/cancer relationship, promotion, anticarcinogenesis, and aging. (JN)

  10. MARINE: THE ULTIMATE SOURCE OF BIOACTIVES AND DRUG METABOLITES

    OpenAIRE

    Jirge Supriya S; Chaudhari Yogesh S

    2010-01-01

    Bioactive compounds from marine flora and fauna have extensive past and present use in the treatment of many diseases and serve as compounds of interest both in their natural form and as templates for synthetic modification. Several molecules isolated from various marine organisms (microorganisms, algae, fungi, invertebrates, and vertebrates) are currently under study at an advanced stage of clinical trials, some of them have already been marketed as drugs. This article gives an overview of c...

  11. Carcinogen risk assessment

    International Nuclear Information System (INIS)

    Hazelwoold, R.N.

    1987-01-01

    This article describes the methods by which risk factors for carcinogenic hazards are determined and the limitations inherent in the process. From statistical and epidemiological studies, the major identifiable factors related to cancer in the United States were determined to be cigarette smoking, diet, reproductive and sexual behavior, infections, ultraviolet and ionizing radiation, and alcohol consumption. The incidence of lung cancer due to air pollutants was estimated to be less than 2%. Research needs were discussed

  12. Smoking out carcinogens

    OpenAIRE

    Baines, David; Griffiths, Huw; Parker, Jane

    2016-01-01

    Smoked foods are becoming increasingly popular and are being produced by large and small food operations, artisan producers, chefs and consumers themselves. Epidemiological studies conducted over a number of decades have linked the consumption of smoked foods with various cancers and these findings have been supported by animal testing. Smoke contains a group of dangerous carcinogens that are responsible for lung cancer in cigarette smokers and implicated as causative agents for colorectal an...

  13. Food derived carcinogenic amnoimidazoazaarenes

    DEFF Research Database (Denmark)

    Frandsen, Henrik

    Carcinogenic aminoimidazoazaarenes are formed during cooking of meat and fish. Important factors for the formation of these compounds are meat type, cooking temperature and time. The compounds are genotoxic in bacterial and mammalian cells. In animal feeding studies the compounds tested so far were...... of the exocyclic amino group. Estimations of human cancer risk have indicated that ingestion of food containing aminoimidazoazaarenes are of importance....

  14. Chromium carcinogenicity: California strategies.

    Science.gov (United States)

    Alexeeff, G V; Satin, K; Painter, P; Zeise, L; Popejoy, C; Murchison, G

    1989-10-01

    Hexavalent chromium was identified by California as a toxic air contaminant (TAC) in January 1986. The California Department of Health Services (CDHS) concurred with the findings of the International Agency for Research on Cancer that there is sufficient evidence to demonstrate the carcinogenicity of chromium in both animals and humans. CDHS did not find any compelling evidence demonstrating the existence of a threshold with respect to chromium carcinogenesis. Experimental data was judged inadequate to assess potential human reproductive risks from ambient exposures. Other health effects were not expected to occur at ambient levels. The theoretically increased lifetime carcinogenic risk from a continuous lifetime exposure to hexavalent chromium fell within the range 12-146 cancer cases per nanogram hexavalent chromium per cubic meter of air per million people exposed, depending on the potency estimate used. The primary sources found to contribute significantly to the risk of exposure were chrome platers, chromic acid anodizing facilities and cooling towers utilizing hexavalent chromium as a corrosion inhibitor. Evaluation of genotoxicity data, animal studies and epidemiological studies indicates that further consideration should be given to the potential carcinogenicity of hexavalent chromium via the oral route.

  15. METABOLISM, GENOTOXICITY, AND CARCINOGENICITY OF COMFREY

    Science.gov (United States)

    Mei, Nan; Guo, Lei; Fu, Peter P.; Fuscoe, James C.; Luan, Yang; Chen, Tao

    2018-01-01

    Comfrey has been consumed by humans as a vegetable and a tea and used as an herbal medicine for more than 2000 years. Comfrey, however, produces hepatotoxicity in livestock and humans and carcinogenicity in experimental animals. Comfrey contains as many as 14 pyrrolizidine alkaloids (PA), including 7-acetylintermedine, 7-acetyllycopsamine, echimidine, intermedine, lasiocarpine, lycopsamine, myoscorpine, symlandine, symphytine, and symviridine. The mechanisms underlying comfrey-induced genotoxicity and carcinogenicity are still not fully understood. The available evidence suggests that the active metabolites of PA in comfrey interact with DNA in liver endothelial cells and hepatocytes, resulting in DNA damage, mutation induction, and cancer development. Genotoxicities attributed to comfrey and riddelliine (a representative genotoxic PA and a proven rodent mutagen and carcinogen) are discussed in this review. Both of these compounds induced similar profiles of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts and similar mutation spectra. Further, the two agents share common mechanisms of drug metabolism and carcinogenesis. Overall, comfrey is mutagenic in liver, and PA contained in comfrey appear to be responsible for comfrey-induced toxicity and tumor induction. PMID:21170807

  16. Metabolism, genotoxicity, and carcinogenicity of comfrey.

    Science.gov (United States)

    Mei, Nan; Guo, Lei; Fu, Peter P; Fuscoe, James C; Luan, Yang; Chen, Tao

    2010-10-01

    Comfrey has been consumed by humans as a vegetable and a tea and used as an herbal medicine for more than 2000 years. Comfrey, however, produces hepatotoxicity in livestock and humans and carcinogenicity in experimental animals. Comfrey contains as many as 14 pyrrolizidine alkaloids (PA), including 7-acetylintermedine, 7-acetyllycopsamine, echimidine, intermedine, lasiocarpine, lycopsamine, myoscorpine, symlandine, symphytine, and symviridine. The mechanisms underlying comfrey-induced genotoxicity and carcinogenicity are still not fully understood. The available evidence suggests that the active metabolites of PA in comfrey interact with DNA in liver endothelial cells and hepatocytes, resulting in DNA damage, mutation induction, and cancer development. Genotoxicities attributed to comfrey and riddelliine (a representative genotoxic PA and a proven rodent mutagen and carcinogen) are discussed in this review. Both of these compounds induced similar profiles of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts and similar mutation spectra. Further, the two agents share common mechanisms of drug metabolism and carcinogenesis. Overall, comfrey is mutagenic in liver, and PA contained in comfrey appear to be responsible for comfrey-induced toxicity and tumor induction.

  17. Report on carcinogens monograph on 1-bromopropane.

    Science.gov (United States)

    2013-09-01

    The National Toxicology Program conducted a cancer evaluation on 1 bromopropane for possible listing in the Report on Carcinogens (RoC). The cancer evaluation is captured in the RoC monograph, which was peer reviewed in a public forum. The monograph consists of two components: (Part 1) the cancer evaluation, which reviews the relevant scientific information, assesses its quality, applies the RoC listing criteria to the scientific information, and provides the NTP recommendation for listing status for 1 bromopropane in the RoC, and (Part 2) the substance profile proposed for the RoC, containing the NTP's listing status recommendation, a summary of the scientific evidence considered key to reaching that decision, and data on properties, use, production, exposure, and Federal regulations and guidelines to reduce exposure to 1-bromopropane. This monograph provides an assessment of the available scientific information on 1 bromopropane, including human exposure and properties, disposition and toxicokinetics, cancer studies in experimental animals, and studies of mechanisms and other related effects, including relevant toxicological effects, genetic toxicology, and mechanisms of carcinogenicity. From this assessment, the NTP recommended that 1 bromopropane be listed as reasonably anticipated to be a human carcinogen in the RoC based on sufficient evidence from studies in experimental animals, which found inhalation exposure to 1-bromopropane caused skin tumors in male rats, large intestine tumors in female and male rats, and lung tumors in female mice. Also noted was that 1 bromopropane, either directly or via reactive metabolites, caused molecular alterations that typically are associated with carcinogenesis, including genotoxicity, oxidative stress, and glutathione depletion. These alterations, observed in mainly in vitro and toxicity studies in rodents, are relevant to possible mechanisms of human carcinogenicity and support the relevance of the cancer studies in

  18. Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard.

    Science.gov (United States)

    Rusyn, Ivan; Chiu, Weihsueh A; Lash, Lawrence H; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z

    2014-01-01

    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. The strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE. © 2013.

  19. Understanding arsenic carcinogenicity by the use of animal models

    International Nuclear Information System (INIS)

    Wanibuchi, Hideki; Salim, Elsayed I.; Kinoshita, Anna; Shen Jun; Wei Min; Morimura, Keiichirou; Yoshida, Kaoru; Kuroda, Koichi; Endo, Ginji; Fukushima, Shoji

    2004-01-01

    Although numerous epidemiological studies have indicated that human arsenic exposure is associated with increased incidences of bladder, liver, skin, and lung cancers, limited attempts have been made to understand mechanisms of carcinogenicity using animal models. Dimethylarsinic acid (DMA), an organic arsenic compound, is a major metabolite of ingested inorganic arsenics in mammals. Recent in vitro studies have proven DMA to be a potent clastogenic agent, capable of inducing DNA damage including double strand breaks and cross-link formation. In our attempts to clarify DMA carcinogenicity, we have recently shown carcinogenic effects of DMA and its related metabolites using various experimental protocols in rats and mice: (1) a multi-organ promotion bioassay in rats; (2) a two-stage promotion bioassay by DMA of rat urinary bladder and liver carcinogenesis; (3) a 2-year carcinogenicity test of DMA in rats; (4) studies on the effects of DMA on lung carcinogenesis in rats; (5) promotion of skin carcinogenesis by DMA in keratin (K6)/ornithine decarboxylase (ODC) transgenic mice; (6) carcinogenicity of DMA in p53(+/-) knockout and Mmh/8-OXOG-DNA glycolase (OGG1) mutant mice; (7) promoting effects of DMA and related organic arsenicals in rat liver; (8) promoting effects of DMA and related organic arsenicals in a rat multi-organ carcinogenesis test; and (9) 2-year carcinogenicity tests of monomethylarsonic acid (MMA) and trimethylarsine oxide (TMAO) in rats. The results revealed that the adverse effects of arsenic occurred either by promoting and initiating carcinogenesis. These data, as covered in the present review, suggest that several mechanisms may be involved in arsenic carcinogenesis

  20. Shear wall ultimate drift limits

    International Nuclear Information System (INIS)

    Duffey, T.A.; Goldman, A.; Farrar, C.R.

    1994-04-01

    Drift limits for reinforced-concrete shear walls are investigated by reviewing the open literature for appropriate experimental data. Drift values at ultimate are determined for walls with aspect ratios ranging up to a maximum of 3.53 and undergoing different types of lateral loading (cyclic static, monotonic static, and dynamic). Based on the geometry of actual nuclear power plant structures exclusive of containments and concerns regarding their response during seismic (i.e.,cyclic) loading, data are obtained from pertinent references for which the wall aspect ratio is less than or equal to approximately 1, and for which testing is cyclic in nature (typically displacement controlled). In particular, lateral deflections at ultimate load, and at points in the softening region beyond ultimate for which the load has dropped to 90, 80, 70, 60, and 50 percent of its ultimate value, are obtained and converted to drift information. The statistical nature of the data is also investigated. These data are shown to be lognormally distributed, and an analysis of variance is performed. The use of statistics to estimate Probability of Failure for a shear wall structure is illustrated

  1. Risk assessment of DNA-reactive carcinogens in food.

    Science.gov (United States)

    Jeffrey, A M; Williams, G M

    2005-09-01

    Risk assessment of DNA-reactive carcinogens in food requires knowledge of the extent of DNA damage in the target organ which results from the competition between DNA adduct formation and repair. Estimates of DNA adduct levels can be made by direct measurement or indirectly as a consequence of their presence, for example, by tumor formation in animal models or exposed populations epidemiologically. Food-borne DNA-reactive carcinogens are present from a variety of sources. They are generally not intrinsically DNA-reactive but require bioactivation to DNA-reactive metabolites a process which may be modulated by the compound itself or the presence of other xenobiotics. A single DNA reactant may form several distinct DNA adducts each undergoing different rates of repair. Some DNA reactants may be photochemically activated or produce reactive oxygen species and thus indirect oxidative DNA damage. The levels of DNA adducts arising from exposures influenced by variations in the doses, the frequency with which an individual is exposed, and rates of DNA repair for specific adducts. Each adduct has a characteristic efficiency with which it induces mutations. Based on experience with the well-studied DNA-reactive food carcinogen aflatoxin B(1) (AFB(1)), a limit of 20 ppb or approximately 30 microg/day has been set and is considered a tolerable daily intake (TDI). Since AFB(1) is considered a potent carcinogen, doses of carcinogens is made.

  2. Carcinogenicity of soil extracts

    Energy Technology Data Exchange (ETDEWEB)

    Shcherbak, N P

    1970-01-01

    A total of 270 3-mo-old mice, hybrids of the C57BL and CBA strains which are highly susceptible to carcinogens, were painted on the skin (2-3 admin./week) with 3-4 drops of (1) a concentrated benzene extract of soil taken near a petroleum refinery with a 3,4 benzpyrene (BP) content of 0.22%; (2) a 0.22% soln of pure BP in benzene; (3) a concentrated benzene extract of soil taken from an old residential area of Moscow (BP content 0.0004%); (4) a 0.0004% BP soln in benzene; and (5) pure benzene. Only mice in the first 2 groups developed tumors. In group (1), 8 mice had papillomas, 46 had skin cancer, 1 had a sarcoma and 2 had plasmocytomas. In group (2) all 60 animals had skin cancer. Lung metastases were present at autopsy in 5 mice in group (1) and in 10 mice in group (2); in some cases, these tumors were multiple. Lymph node metastases were found in 6 mice in group (1) and in 10 mice in group (2). Tumors developed more slowly in group (1) than in group (2).

  3. Ultimate disposal of radioactive wastes

    International Nuclear Information System (INIS)

    Roethemeyer, H.

    1991-01-01

    The activities developed by the Federal Institution of Physical Engineering PTB and by the Federal Office for Radiation Protection (BfS) concentrated, among others, on work to implement ultimate storage facilities for radioactive wastes. The book illuminates this development from site designation to the preliminary evaluation of the Gorleben salt dome, to the preparation of planning documents proving that the Konrad ore mine is suitable for a repository. The paper shows the legal provisions involved; research and development tasks; collection of radioactive wastes ready for ultimate disposal; safety analysis in the commissioning and post-operational stages, and product control. The historical development of waste management in the Federal Republic of Germany and international cooperation in this area are outlined. (DG) [de

  4. Ultimate fate of constrained voters

    International Nuclear Information System (INIS)

    Vazquez, F; Redner, S

    2004-01-01

    We examine the ultimate fate of individual opinions in a socially interacting population of leftists, centrists and rightists. In an elemental interaction between agents, a centrist and a leftist can both become centrists or both become leftists with equal rates (and similarly for a centrist and a rightist). However leftists and rightists do not interact. This interaction step between pairs of agents is applied repeatedly until the system can no longer evolve. In the mean-field limit, we determine the exact probability that the system reaches consensus (either leftist, rightist or centrist) or a frozen mixture of leftists and rightists as a function of the initial composition of the population. We also determine the mean time until the final state is reached. Some implications of our results for the ultimate fate in a limit of the Axelrod model are discussed

  5. Ultimate fate of constrained voters

    Energy Technology Data Exchange (ETDEWEB)

    Vazquez, F [Department of Physics, Center for BioDynamics, Boston University, Boston, MA 02215 (United States); Redner, S [Department of Physics, Center for Polymer Studies, Boston University, Boston, MA 02215 (United States)

    2004-09-03

    We examine the ultimate fate of individual opinions in a socially interacting population of leftists, centrists and rightists. In an elemental interaction between agents, a centrist and a leftist can both become centrists or both become leftists with equal rates (and similarly for a centrist and a rightist). However leftists and rightists do not interact. This interaction step between pairs of agents is applied repeatedly until the system can no longer evolve. In the mean-field limit, we determine the exact probability that the system reaches consensus (either leftist, rightist or centrist) or a frozen mixture of leftists and rightists as a function of the initial composition of the population. We also determine the mean time until the final state is reached. Some implications of our results for the ultimate fate in a limit of the Axelrod model are discussed.

  6. Aspergillus flavus secondary metabolites: more than just aflatoxins

    Science.gov (United States)

    Aspergillus flavus is best known for producing the family of potent carcinogenic secondary metabolites known as aflatoxins. However, this opportunistic plant and animal pathogen also produces numerous other secondary metabolites, many of which have also been shown to be toxic. While about forty of t...

  7. Experimental investigation of ultimate loads

    Energy Technology Data Exchange (ETDEWEB)

    Petersen, S M; Larsen, G C; Antoniou, I; Lind, S O; Courtney, M [Risoe National Lab., Wind Energy and Atmospheric Physics, Roskilde (Denmark)

    1999-03-01

    Verification of the structural integrity of a wind turbine involves analysis of fatigue loading as well as ultimate loading. With the trend of persistently growing turbines, the ultimate loading seems to become relatively more important. For wind turbines designed according to the wind conditions prescribed in the IEC-61400 code, the ultimate load is often identified as the leading load parameter. Exemplified by the use of an extensive measurement campaign a procedure for evaluation of the extreme flap-wise bending moments, occurring during normal operating of a wind turbine, is presented. The structural measurements are made on a NEG Micon 650 kW wind turbine erected at a complex high wind site in Oak Creek, California. The turbine is located on the top of a ridge. The prevailing wind direction is perpendicular to the ridge, and the annual mean wind speed is 9.5 m/s. The associated wind field measurement, are taken from two instrumented masts erected less than one rotor diameter in front of the turbine in direction of the prevailing wind direction. Both masts are instrumented at different heights in order to gain insight of the 3D-wind speed structure over the entire rotor plane. Extreme distributions, associated with a recurrence period of 10 minutes, conditioned on the mean wind speed and the turbulence intensity are derived. Combined with the wind climate model proposed in the IEC standard, these distributions are used to predict extreme distributions with recurrence periods equal to one and fifty years, respectively. The synthesis of the conditioned PDF`s and the wind climate model is performed by means of Monte Carlo simulation. (au)

  8. Ultimate Explanations of the Universe

    CERN Document Server

    Heller, Michael

    2009-01-01

    We humans are collectively driven by a powerful - yet not fully explained - instinct to understand. We would like to see everything established, proven, laid bare. The more important an issue, the more we desire to see it clarified, stripped of all secrets, all shades of gray. What could be more important than to understand the Universe and ourselves as a part of it? To find a window onto our origin and our destiny? This book examines how far our modern cosmological theories - with their sometimes audacious models, such as inflation, cyclic histories, quantum creation, parallel universes - can take us towards answering these questions. Can such theories lead us to ultimate truths, leaving nothing unexplained? Last, but not least, Heller addresses the thorny problem of why and whether we should expect to find theories with all-encompassing explicative power.

  9. Ultimate loading of wind turbines

    DEFF Research Database (Denmark)

    Larsen, Gunner Chr.; Ronold, K.; Ejsing Jørgensen, Hans

    1999-01-01

    An extreme loading study has been conducted comprising a general wind climate analysis as well as a wind turbine reliability study. In the wind climate analysis, the distribution of the (horizontal) turbulence standard deviation, conditioned on the meanwind speed, has been approximated by fitting......, a design turbulence intensity for off-shore application is proposed which, in the IEC code framework, is applicable for extreme as well as for fatigue loaddetermination. In order to establish a rational method to analyse wind turbine components with respect to failure in ultimate loading, and in addition...... a three parameter Weibull distribution to the measured on-shore and off-shore data for wind speed variations. Specific recommendations on off-shore design turbulence intensities are lacking in the presentIEC-code. Based on the present analysis of the off-shore wind climate on two shallow water sites...

  10. Ultimate explanations and suboptimal choice.

    Science.gov (United States)

    Vasconcelos, Marco; Machado, Armando; Pandeirada, Josefa N S

    2018-07-01

    Researchers have unraveled multiple cases in which behavior deviates from rationality principles. We propose that such deviations are valuable tools to understand the adaptive significance of the underpinning mechanisms. To illustrate, we discuss in detail an experimental protocol in which animals systematically incur substantial foraging losses by preferring a lean but informative option over a rich but non-informative one. To understand how adaptive mechanisms may fail to maximize food intake, we review a model inspired by optimal foraging principles that reconciles sub-optimal choice with the view that current behavioral mechanisms were pruned by the optimizing action of natural selection. To move beyond retrospective speculation, we then review critical tests of the model, regarding both its assumptions and its (sometimes counterintuitive) predictions, all of which have been upheld. The overall contention is that (a) known mechanisms can be used to develop better ultimate accounts and that (b) to understand why mechanisms that generate suboptimal behavior evolved, we need to consider their adaptive value in the animal's characteristic ecology. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Cell-mediated mutagenesis and cell transformation of mammalian cells by chemical carcinogens

    International Nuclear Information System (INIS)

    Huberman, E.; Langenbach, R.

    1977-01-01

    We have developed a cell-mediated mutagenesis assay in which cells with the appropriate markers for mutagenesis are co-cultivated with either lethally irradiated rodent embryonic cells that can metabolize carcinogenic hydrocarbons or with primary rat liver cells that can metabolize chemicals carcinogenic to the liver. During co-cultivation, the reactive metabolites of the procarcinogen appear to be transmitted to the mutable cells and induce mutations in them. Assays of this type make it possible to demonstrate a relationship between carcinogenic potency of the chemicals and their ability to induce mutations in mammalian cells. In addition, by simultaneously comparing the frequencies of transformation and mutation induced in normal diploid hamster cells by benzo(a)pyrene (BP) and one of its metabolites, it is possible to estimate the genetic target size for cell transformation in vitro

  12. Risk assessment of DNA-reactive carcinogens in food

    International Nuclear Information System (INIS)

    Jeffrey, A.M.; Williams, G.M.

    2005-01-01

    Risk assessment of DNA-reactive carcinogens in food requires knowledge of the extent of DNA damage in the target organ which results from the competition between DNA adduct formation and repair. Estimates of DNA adduct levels can be made by direct measurement or indirectly as a consequence of their presence, for example, by tumor formation in animal models or exposed populations epidemiologically. Food-borne DNA-reactive carcinogens are present from a variety of sources. They are generally not intrinsically DNA-reactive but require bioactivation to DNA-reactive metabolites a process which may be modulated by the compound itself or the presence of other xenobiotics. A single DNA reactant may form several distinct DNA adducts each undergoing different rates of repair. Some DNA reactants may be photochemically activated or produce reactive oxygen species and thus indirect oxidative DNA damage. The levels of DNA adducts arising from exposures influenced by variations in the doses, the frequency with which an individual is exposed, and rates of DNA repair for specific adducts. Each adduct has a characteristic efficiency with which it induces mutations. Based on experience with the well-studied DNA-reactive food carcinogen aflatoxin B 1 (AFB 1 ), a limit of 20 ppb or ∼30 μg/day has been set and is considered a tolerable daily intake (TDI). Since AFB 1 is considered a potent carcinogen, doses of 32 P-postlabeling or the use of surrogates such as hemoglobin adducts, together with approaches to evaluate the results. A discussion of approaches to estimating possible threshold effects for DNA-reactive carcinogens is made

  13. Effects of aspartame metabolites on astrocytes and neurons.

    Science.gov (United States)

    Rycerz, Karol; Jaworska-Adamu, Jadwiga Elżbieta

    2013-01-01

    Aspartame, a widespread sweetener used in many food products, is considered as a highly hazardous compound. Aspartame was discovered in 1965 and raises a lot of controversy up to date. Astrocytes are glial cells, the presence and functions of which are closely connected with the central nervous system (CNS). The aim of this article is to demonstrate the direct and indirect role of astrocytes participating in the harmful effects of aspartame metabolites on neurons. The artificial sweetener is broken down into phenylalanine (50%), aspartic acid (40%) and methanol (10%) during metabolism in the body. The excess of phenylalanine blocks the transport of important amino acids to the brain contributing to reduced levels of dopamine and serotonin. Astrocytes directly affect the transport of this amino acid and also indirectly by modulation of carriers in the endothelium. Aspartic acid at high concentrations is a toxin that causes hyperexcitability of neurons and is also a precursor of other excitatory amino acid - glutamates. Their excess in quantity and lack of astrocytic uptake induces excitotoxicity and leads to the degeneration of astrocytes and neurons. The methanol metabolites cause CNS depression, vision disorders and other symptoms leading ultimately to metabolic acidosis and coma. Astrocytes do not play a significant role in methanol poisoning due to a permanent consumption of large amounts of aspartame. Despite intense speculations about the carcinogenicity of aspartame, the latest studies show that its metabolite - diketopiperazine - is cancirogenic in the CNS. It contributes to the formation of tumors in the CNS such as gliomas, medulloblastomas and meningiomas. Glial cells are the main source of tumors, which can be caused inter alia by the sweetener in the brain. On the one hand the action of astrocytes during aspartame poisoning may be advantageous for neuro-protection while on the other it may intensify the destruction of neurons. The role of the glia in

  14. The dream of an ultimate theory

    International Nuclear Information System (INIS)

    Weinberg, S.

    1997-10-01

    Steven Weinberg describes how the dream of an ultimate theory began when one tried to unify the fundamental laws governing the stars constellations as elementary particles: electromagnetism, weak-electro theory then standard model which gives only one quantity out of its fields, the gravitation. He tries to explain to what an ultimate theory could look like. but the dream of an ultimate theory is not yet realized, there are some elementary particles to find before and then to build superconducting super colliders. The europe made it. the dream of an ultimate theory became an european dream. (N.C.)

  15. In vitro screening of inhibition of PPAR-γ activity as a first step in identification of potential breast carcinogens

    DEFF Research Database (Denmark)

    Kopp, Tine Iskov; Lundqvist, J.; Petersen, R. K.

    2015-01-01

    and estrogen biosynthesis ultimately leading to breast cancer. If other organic solvents inhibit PPAR-γ activity, they should also lead to increased oestrogen biosynthesis and thus be potential breast carcinogens. Ten commonly used hydrophilic organic solvents were first tested in a cell-based screening assay...... followed by a well-established steroidogenesis assay for production of sex hormones in exposed H295 R cells may provide a screening tool for potential breast carcinogens. This initial screening thus identified ethylene glycol and possibly ethyl acetate as potential breast carcinogens....

  16. Risk Assessment Approaches for Carcinogenic Food Contaminants

    OpenAIRE

    Gillespie, Zoe; Pulido, Olga; Vavasour, Elizabeth

    2011-01-01

    Health Canada has identified the need for a standardized department-wide approach for the risk assessment of carcinogens in foods (e.g., pesticides, food chemical contaminants, veterinary therapeutics). A standardized approach would better facilitate and inform risk management strategies for the control of human exposure to food sources of carcinogens. Within the post- market regulatory context, directly DNA-reactive carcinogens are of most concern because any exposure is theoretically assume...

  17. Concussion Prevalence in Competitive Ultimate Frisbee Players

    Science.gov (United States)

    Lazar, Damien J.; Lichtenstein, Jonathan D.; Tybor, David J.

    2018-01-01

    Background: Ultimate Frisbee (ultimate) is a fast-growing, popular sport played nationally by over 4 million athletes. While several studies have examined injury rates in ultimate, no work has investigated the prevalence of concussions specifically or players’ knowledge and management of those injuries. Purpose: To estimate the lifetime prevalence of concussions in ultimate and to assess players’ knowledge of concussions as well as their concussion management behaviors. Study Design: Descriptive epidemiology study. Methods: From June to November 2015, we collected ultimate-related concussion data via an anonymous web-based survey, the Concussion in Ultimate Frisbee Survey, from a convenience sample of 787 male and female ultimate players across the United States. Results: There were 553 male and 234 female respondents included in the analysis; 26.58% of men and 24.79% of women reported that they had sustained at least 1 concussion while playing ultimate, with 45.58% and 43.10% of those men and women, respectively, reporting multiple concussions. A total of 67.81% of men and 78.21% of women stated that they would remove themselves from play after sustaining a given concussion, although 45.99% of men and 37.62% of women indicated that they had returned to play in the same game or practice. Conclusion: Our preliminary data suggest that concussions do commonly occur in competitive ultimate and that better education and management of concussions in ultimate athletes are needed. This study is an important first step in deepening our understanding of these issues. PMID:29552572

  18. Carcinogenicity assessments of biotechnology-derived pharmaceuticals: a review of approved molecules and best practice recommendations.

    Science.gov (United States)

    Vahle, John L; Finch, Gregory L; Heidel, Shawn M; Hovland, David N; Ivens, Inge; Parker, Suezanne; Ponce, Rafael A; Sachs, Clifford; Steigerwalt, Ronald; Short, Brian; Todd, Marque D

    2010-06-01

    An important safety consideration for developing new therapeutics is assessing the potential that the therapy will increase the risk of cancer. For biotherapeutics, traditional two-year rodent bioassays are often not scientifically applicable or feasible. This paper is a collaborative effort of industry toxicologists to review past and current practice regarding carcinogenicity assessments of biotherapeutics and to provide recommendations. Publicly available information on eighty marketed protein biotherapeutics was reviewed. In this review, no assessments related to carcinogenicity or tumor growth promotion were identified for fifty-one of the eighty molecules. For the twenty-nine biotherapeutics in which assessments related to carcinogenicity were identified, various experimental approaches were employed. This review also discusses several key principles to aid in the assessment of carcinogenic potential, including (1) careful consideration of mechanism of action to identify theoretical risks, (2) careful investigation of existing data for indications of proliferative or immunosuppressive potential, and (3) characterization of any proliferative or immunosuppressive signals detected. Traditional two-year carcinogenicity assays should not be considered as the default method for assessing the carcinogenicity potential of biotherapeutics. If experimentation is considered warranted, it should be hypothesis driven and may include a variety of experimental models. Ultimately, it is important that preclinical data provide useful guidance in product labeling.

  19. Morphine metabolites

    DEFF Research Database (Denmark)

    Christrup, Lona Louring

    1997-01-01

    , morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) are the major metabolites of morphine. The metabolism of morphine occurs not only in the liver, but may also take place in the brain and the kidneys. The glucuronides are mainly eliminated via bile and urine. Glucuronides as a rule...... are considered as highly polar metabolites unable to cross the blood-brain barrier. Although morphine glucuronidation has been demonstrated in human brain tissue, the capacity is very low compared to that of the liver, indicating that the M3G and M6G concentrations observed in the cerebrospinal fluid (CSF) after...... systemic administration reflect hepatic metabolism of morphine and that the morphine glucuronides, despite their high polarity, can penetrate into the brain. Like morphine, M6G has been shown to be relatively more selective for mu-receptors than for delta- and kappa-receptors while M3G does not appear...

  20. Physical demands in competitive ultimate frisbee

    DEFF Research Database (Denmark)

    Krustrup, Peter; Mohr, Magni

    2015-01-01

    The objective was to study game demands in competitive ultimate Frisbee by performing match analysis during a game. Thirteen moderately trained (Yo-Yo intermittent recovery test levels 1 and 2 [Yo-Yo IR1 and IR2] performance: 1790 ± 382 m and 657 ± 225 m, respectively) competitive male ultimate...... = 0.74, p ≤ 0.05). Ultimate Frisbee is an intense intermittent team sport with high cardiovascular loading and clear indications of fatigue toward the end of each half. Yo-Yo IR test performances correlate with physical match performance....

  1. Environmental exposure to carcinogens in northwestern Cameroon

    African Journals Online (AJOL)

    EB

    2013-09-03

    Sep 3, 2013 ... Twenty-nine (69.0%) [95% CI: 47.0 – 75.0] participants could smell the carcinogenic chemicals they use. Thirty. (71.4%) [95% CI: 65.0 – 77.0] participants had been instructed in the use of protective equipment against carcinogens. Participants used preventive devices like hand gloves, laboratory coats, ...

  2. Risk assessment of carcinogens in food

    International Nuclear Information System (INIS)

    Barlow, Susan; Schlatter, Josef

    2010-01-01

    Approaches for the risk assessment of carcinogens in food have evolved as scientific knowledge has advanced. Early methods allowed little more than hazard identification and an indication of carcinogenic potency. Evaluation of the modes of action of carcinogens and their broad division into genotoxic and epigenetic (non-genotoxic, non-DNA reactive) carcinogens have played an increasing role in determining the approach followed and provide possibilities for more detailed risk characterisation, including provision of quantitative estimates of risk. Reliance on experimental animal data for the majority of risk assessments and the fact that human exposures to dietary carcinogens are often orders of magnitude below doses used in experimental studies has provided a fertile ground for discussion and diverging views on the most appropriate way to offer risk assessment advice. Approaches used by national and international bodies differ, with some offering numerical estimates of potential risks to human health, while others express considerable reservations about the validity of quantitative approaches requiring extrapolation of dose-response data below the observed range and instead offer qualitative advice. Recognising that qualitative advice alone does not provide risk managers with information on which to prioritise the need for risk management actions, a 'margin of exposure' approach for substances that are both genotoxic and carcinogenic has been developed, which is now being used by the World Health Organization and the European Food Safety Authority. This review describes the evolution of risk assessment advice on carcinogens and discusses examples of ways in which carcinogens in food have been assessed in Europe.

  3. Risk assessment of carcinogens in food.

    Science.gov (United States)

    Barlow, Susan; Schlatter, Josef

    2010-03-01

    Approaches for the risk assessment of carcinogens in food have evolved as scientific knowledge has advanced. Early methods allowed little more than hazard identification and an indication of carcinogenic potency. Evaluation of the modes of action of carcinogens and their broad division into genotoxic and epigenetic (non-genotoxic, non-DNA reactive) carcinogens have played an increasing role in determining the approach followed and provide possibilities for more detailed risk characterisation, including provision of quantitative estimates of risk. Reliance on experimental animal data for the majority of risk assessments and the fact that human exposures to dietary carcinogens are often orders of magnitude below doses used in experimental studies has provided a fertile ground for discussion and diverging views on the most appropriate way to offer risk assessment advice. Approaches used by national and international bodies differ, with some offering numerical estimates of potential risks to human health, while others express considerable reservations about the validity of quantitative approaches requiring extrapolation of dose-response data below the observed range and instead offer qualitative advice. Recognising that qualitative advice alone does not provide risk managers with information on which to prioritise the need for risk management actions, a "margin of exposure" approach for substances that are both genotoxic and carcinogenic has been developed, which is now being used by the World Health Organization and the European Food Safety Authority. This review describes the evolution of risk assessment advice on carcinogens and discusses examples of ways in which carcinogens in food have been assessed in Europe.

  4. Environmental exposure to carcinogens in northwestern Cameroon ...

    African Journals Online (AJOL)

    African Health Sciences ... Humans can prevent themselves from a number of workplace and environmental carcinogens. ... Methods: A structured questionnaire was used to collect information on carcinogen exposure in the workplace and environment through trained field staff from volunteers after gaining informed ...

  5. Ultimate and proximate explanations of strong reciprocity.

    Science.gov (United States)

    Vromen, Jack

    2017-08-23

    Strong reciprocity (SR) has recently been subject to heated debate. In this debate, the "West camp" (West et al. in Evol Hum Behav 32(4):231-262, 2011), which is critical of the case for SR, and the "Laland camp" (Laland et al. in Science, 334(6062):1512-1516, 2011, Biol Philos 28(5):719-745, 2013), which is sympathetic to the case of SR, seem to take diametrically opposed positions. The West camp criticizes advocates of SR for conflating proximate and ultimate causation. SR is said to be a proximate mechanism that is put forward by its advocates as an ultimate explanation of human cooperation. The West camp thus accuses advocates of SR for not heeding Mayr's original distinction between ultimate and proximate causation. The Laland camp praises advocates of SR for revising Mayr's distinction. Advocates of SR are said to replace Mayr's uni-directional view on the relation between ultimate and proximate causes by the bi-directional one of reciprocal causation. The paper argues that both the West camp and the Laland camp misrepresent what advocates of SR are up to. The West camp is right that SR is a proximate cause of human cooperation. But rather than putting forward SR as an ultimate explanation, as the West camp argues, advocates of SR believe that SR itself is in need of ultimate explanation. Advocates of SR tend to take gene-culture co-evolutionary theory as the correct meta-theoretical framework for advancing ultimate explanations of SR. Appearances notwithstanding, gene-culture coevolutionary theory does not imply Laland et al.'s notion of reciprocal causation. "Reciprocal causation" suggests that proximate and ultimate causes interact simultaneously, while advocates of SR assume that they interact sequentially. I end by arguing that the best way to understand the debate is by disambiguating Mayr's ultimate-proximate distinction. I propose to reserve "ultimate" and "proximate" for different sorts of explanations, and to use other terms for distinguishing

  6. It is time to regulate carcinogenic tobacco-specific nitrosamines in cigarette tobacco

    Science.gov (United States)

    Hecht, Stephen S.

    2014-01-01

    The Family Smoking Prevention and Tobacco Control Act gives the Food and Drug Administration power to regulate tobacco products. This commentary calls for immediate regulation of the carcinogenic tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N’-nitrosonornicotine (NNN) in cigarette tobacco as a logical path to cancer prevention. NNK and NNN, powerful carcinogens in laboratory animals, have been evaluated as “carcinogenic to humans” by the International Agency for Research on Cancer. NNK and NNN are present in the tobacco of virtually all marketed cigarettes; levels in cigarette smoke are directly proportional to the amounts in tobacco. The NNK metabolite NNAL, itself a strong carcinogen, is present in the urine of smokers and non-smokers exposed to secondhand smoke. Some of the highest levels of NNK and NNN are found in U.S. products. It is well established that factors such as choice of tobacco blend, agricultural conditions, and processing methods influence levels of NNK and NNN in cigarette tobacco and cigarette smoke. Therefore, it is time to control these factors and produce cigarettes with 100 ppb or less each of NNK and NNN in tobacco, which would result in an approximate 15-20 fold reduction of these carcinogens in the mainstream smoke of popular cigarettes sold in the United States. PMID:24806664

  7. Capturing Labile Sulfenamide and Sulfinamide Serum Albumin Adducts of Carcinogenic Arylamines by Chemical Oxidation

    Science.gov (United States)

    Peng, Lijuan; Turesky, Robert J.

    2013-01-01

    Aromatic amines and heterocyclic aromatic amines (HAAs) are a class of structurally related carcinogens that are formed during the combustion of tobacco or during the high temperature cooking of meats. These procarcinogens undergo metabolic activation by N-oxidation of the exocyclic amine group to produce N-hydroxylated metabolites, which are critical intermediates implicated in toxicity and DNA damage. The arylhydroxylamines and their oxidized arylnitroso derivatives can also react with cysteine (Cys) residues of glutathione or proteins to form, respectively, sulfenamide and sulfinamide adducts. However, sulfur-nitrogen linked adducted proteins are often difficult to detect because they are unstable and undergo hydrolysis during proteolytic digestion. Synthetic N-oxidized intermediates of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a carcinogenic HAA produced in cooked meats, and 4-aminobiphenyl, a carcinogenic aromatic amine present in tobacco smoke were reacted with human serum albumin (SA) and formed labile sulfenamide or sulfinamide adducts at the Cys34 residue. Oxidation of the carcinogen-modified SA with m-chloroperoxybenzoic acid (m-CPBA) produced the arylsulfonamide adducts, which were stable to heat and the chemical reduction conditions employed to denature SA. The sulfonamide adducts of PhIP and 4-ABP were identified, by liquid chromatography/mass spectrometry, in proteolytic digests of denatured SA. Thus, selective oxidation of arylamine-modified SA produces stable arylsulfonamide-SA adducts, which may serve as biomarkers of these tobacco and dietary carcinogens. PMID:23240913

  8. Dose-response relationships for carcinogens: a review

    International Nuclear Information System (INIS)

    Zeise, L.; Wilson, R.; Crouch, E.A.C.

    1987-01-01

    The authors review the experimental evidence for various shapes of dose-response relationships for carcinogens and summarize those experiments that give the most information on relatively low doses. A brief review of some models is given to illustrate the shapes of dose-response curve expected from them. Their major interest is in the use of dose-response relationships to estimate risks to humans at low doses, and so they pay special attention to experimentally observed and theoretically expected nonlinearities. There are few experimental examples of nonlinear dose-response relations in humans, but this may simply be due to the limitations in the data. The several examples in rodents, even though for high dose data, suggest that nonlinearity is common. In some cases such nonlinearities may be rationalized on the basis of the pharmacokinetics of the test compound or its metabolites

  9. Metabolic activation of the bladder carcinogen 4-nitrobiphenyl (NBP)

    International Nuclear Information System (INIS)

    Swaminathan, S.

    1986-01-01

    The metabolism of NBP, a dog bladder carcinogen, was examined in vitro using rat liver tissues. NBP was metabolized by enzymes localized both in the microsomes and cytosol. The microsomal enzyme activity was inducible by Aroclor 1254 and phenobarbital. High pressure liquid chromatography analysis of the ethyl acetate extract of the reaction mixture, following incubation of [ 3 H]NBP with NADPH and microsomes, revealed four radioactive and UV absorbing peaks with retention times of 5, 8, 14 and 28 min. The peaks at 8, 14 and 28 min corresponded with 4-aminobiphenyl (ABP), NBP and azoxy biphenyl, respectively. The early eluting component with a retention time of 5 min has been tentatively identified as a ring hydroxylated derivative. In contrast to microsomal metabolism, cytosol-mediated metabolism yielded only one major metabolite identified as ABP. Cytosol-mediate reduction was inhibited by the xanthine oxidase inhibitor allopurinol. In vitro incubation of NBP with NADH and commercial preparations of xanthine oxidase also yielded ABP and the formation of the latter was blocked by allopurinol. Xanthine oxidase catalyzed also the binding of [ 3 H]NBP to DNA and proteins; the binding was inhibited by allopurinol. These data support the hypothesis that the nitro reduction step is involved in the activation of the bladder carcinogen NBP, and that the nitroreductases occur in both the microsomes and cytosol. The cytosolic activity is primarily due to xanthine oxidase

  10. Ultimate justification: Wittgenstein and medical ethics.

    Science.gov (United States)

    Hughes, J

    1995-02-01

    Decisions must be justified. In medical ethics various grounds are given to justify decisions, but ultimate justification seems illusory and little considered. The philosopher Wittgenstein discusses the problem of ultimate justification in the context of general philosophy. His comments, nevertheless, are pertinent to ethics. From a discussion of Wittgensteinian notions, such as 'bedrock', the idea that 'ultimate' justification is grounded in human nature as such is derived. This discussion is relevant to medical ethics in at least five ways: it shows generally what type of certainty there is in practical ethics; it seems to imply some objective foundation to our ethical judgements; it squares with our experience of making ethical decisions; it shows something of the nature of moral arguments; and, finally, it has implications for teaching medicine and ethics.

  11. Librarians Are the Ultimate Knowledge Managers?

    Science.gov (United States)

    Koina, Cathie

    2003-01-01

    Librarians are the ultimate knowledge managers. Everyone knows that. After all, haven't they been the custodians of documented knowledge for centuries? Who could possibly do it better than them? Well, then why aren't people knocking down their doors, begging them to be the knowledge managers of the organisation? Are they just ignorant of how…

  12. Biomarkers of carcinogen exposure and early effects.

    OpenAIRE

    2006-01-01

    The purpose of this review is to summarise the current situation regarding the types and uses of biomarkers of exposure and effect for the main classes of food-derived genotoxic carcinogens, and to consider some aspects of the intercomparison between these biomarkers. The biomarkers of exposure and early effects of carcinogens that have been most extensively developed are those for genotoxic agents and for compounds that generate hydroxyl radicals and other reactive radical species, and it is...

  13. Mutagenic and carcinogenic properties of drinking water

    International Nuclear Information System (INIS)

    Kool, H.J.; van Kreijl, C.F.; Hrubec, J.

    1985-01-01

    In this chapter results of oxidation treatments with chlorine, ozone, chlorine dioxide, and ultraviolet (UV), with respect to their effects on activity (Ames test) in drinking water supplies are reviewed. In addition, the authors present the preliminary results of a pilot plant study on the effects of chlorine and chlorine dioxide on mutagenicity. Furthermore, results of several carcinogenicity studies performed with organic drinking water concentrates are discussed in relation to the results of a Dutch carcinogenicity study with mutagenic drinking water concentrates

  14. Predictive Models for Carcinogenicity and Mutagenicity ...

    Science.gov (United States)

    Mutagenicity and carcinogenicity are endpoints of major environmental and regulatory concern. These endpoints are also important targets for development of alternative methods for screening and prediction due to the large number of chemicals of potential concern and the tremendous cost (in time, money, animals) of rodent carcinogenicity bioassays. Both mutagenicity and carcinogenicity involve complex, cellular processes that are only partially understood. Advances in technologies and generation of new data will permit a much deeper understanding. In silico methods for predicting mutagenicity and rodent carcinogenicity based on chemical structural features, along with current mutagenicity and carcinogenicity data sets, have performed well for local prediction (i.e., within specific chemical classes), but are less successful for global prediction (i.e., for a broad range of chemicals). The predictivity of in silico methods can be improved by improving the quality of the data base and endpoints used for modelling. In particular, in vitro assays for clastogenicity need to be improved to reduce false positives (relative to rodent carcinogenicity) and to detect compounds that do not interact directly with DNA or have epigenetic activities. New assays emerging to complement or replace some of the standard assays include VitotoxTM, GreenScreenGC, and RadarScreen. The needs of industry and regulators to assess thousands of compounds necessitate the development of high-t

  15. Ultimate gradient in solid-state accelerators

    International Nuclear Information System (INIS)

    Whittum, D.H.

    1998-08-01

    The authors recall the motivation for research in high-gradient acceleration and the problems posed by a compact collider. They summarize the phenomena known to appear in operation of a solid-state structure with large fields, and research relevant to the question of the ultimate gradient. They take note of new concepts, and examine one in detail, a miniature particle accelerator based on an active millimeter-wave circuit and parallel particle beams

  16. The ultimate disposition of depleted uranium

    Energy Technology Data Exchange (ETDEWEB)

    Lemons, T.R. [Uranium Enrichment Organization, Oak Ridge, TN (United States)

    1991-12-31

    Depleted uranium (DU) is produced as a by-product of the uranium enrichment process. Over 340,000 MTU of DU in the form of UF{sub 6} have been accumulated at the US government gaseous diffusion plants and the stockpile continues to grow. An overview of issues and objectives associated with the inventory management and the ultimate disposition of this material is presented.

  17. Ultimate Strength of Ship Hulls under Torsion

    DEFF Research Database (Denmark)

    Paik, Jeom Kee; Thayamballi, Anil K.; Pedersen, Preben Terndrup

    2001-01-01

    For a ship hull with large deck openings such as container vessels and some large bulk carriers, the analysis of warping stresses and hatch opening deformations is an essential part of ship structural analyses. It is thus of importance to better understand the ultimate torsional strength characte......For a ship hull with large deck openings such as container vessels and some large bulk carriers, the analysis of warping stresses and hatch opening deformations is an essential part of ship structural analyses. It is thus of importance to better understand the ultimate torsional strength...... characteristics of ships with large hatch openings. The primary aim of the present study is to investigate the ultimate strength characteristics of ship hulls with large hatch openings under torsion. Axial (warping) as well as shear stresses are normally developed for thin-walled beams with open cross sections...... subjected to torsion. A procedure for calculating these stresses is briefly described. As an illustrative example, the distribution and magnitude of warping and shear stresses for a typical container vessel hull cross section under unit torsion is calculated by the procedure. By theoretical and numerical...

  18. Environmental exposure to human carcinogens in teenagers and the association with DNA damage

    International Nuclear Information System (INIS)

    Franken, Carmen; Koppen, Gudrun; Lambrechts, Nathalie; Govarts, Eva; Bruckers, Liesbeth; Den Hond, Elly; Loots, Ilse; Nelen, Vera; Sioen, Isabelle; Nawrot, Tim S.; Baeyens, Willy; Van Larebeke, Nicolas; Boonen, Francis; Ooms, Daniëlla; Wevers, Mai; Jacobs, Griet; Covaci, Adrian; Schettgen, Thomas; Schoeters, Greet

    2017-01-01

    Background: We investigated whether human environmental exposure to chemicals that are labeled as (potential) carcinogens leads to increased (oxidative) damage to DNA in adolescents. Material and methods: Six hundred 14–15-year-old youngsters were recruited all over Flanders (Belgium) and in two areas with important industrial activities. DNA damage was assessed by alkaline and formamidopyrimidine DNA glycosylase (Fpg) modified comet assays in peripheral blood cells and analysis of urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. Personal exposure to potentially carcinogenic compounds was measured in urine, namely: chromium, cadmium, nickel, 1-hydroxypyrene as a proxy for exposure to other carcinogenic polycyclic aromatic hydrocarbons (PAHs), t,t-muconic acid as a metabolite of benzene, 2,5-dichlorophenol (2,5-DCP), organophosphate pesticide metabolites, and di(2-ethylhexyl) phthalate (DEHP) metabolites. In blood, arsenic, polychlorinated biphenyl (PCB) congeners 118 and 156, hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT) and perfluorooctanoic acid (PFOA) were analyzed. Levels of methylmercury (MeHg) were measured in hair. Multiple linear regression models were used to establish exposure-response relationships. Results: Biomarkers of exposure to PAHs and urinary chromium were associated with higher levels of both 8-OHdG in urine and DNA damage detected by the alkaline comet assay. Concentrations of 8-OHdG in urine increased in relation with increasing concentrations of urinary t,t-muconic acid, cadmium, nickel, 2,5-DCP, and DEHP metabolites. Increased concentrations of PFOA in blood were associated with higher levels of DNA damage measured by the alkaline comet assay, whereas DDT was associated in the same direction with the Fpg-modified comet assay. Inverse associations were observed between blood arsenic, hair MeHg, PCB 156 and HCB, and urinary 8-OHdG. The latter exposure biomarkers were also associated with higher fish intake. Urinary nickel

  19. Environmental exposure to human carcinogens in teenagers and the association with DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Franken, Carmen, E-mail: carmen.franken@vito.be [Flemish Institute for Technological Research (VITO), Mol (Belgium); Department of Biomedical Sciences, University of Antwerp, Antwerp (Belgium); Koppen, Gudrun; Lambrechts, Nathalie; Govarts, Eva [Flemish Institute for Technological Research (VITO), Mol (Belgium); Bruckers, Liesbeth [Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt University, Hasselt (Belgium); Den Hond, Elly [Flemish Institute for Technological Research (VITO), Mol (Belgium); Loots, Ilse [Political and Social Sciences, University of Antwerp, Antwerp (Belgium); Nelen, Vera [Provincial Institute for Hygiene, Antwerp (Belgium); Sioen, Isabelle [Department of Public Health, Ghent University, Ghent (Belgium); Department of Food Safety and Food Quality, Ghent University, Ghent (Belgium); Nawrot, Tim S. [Centre for Environmental Sciences, Hasselt University, Diepenbeek (Belgium); Department of Public Health & Primary Care, Leuven University, Leuven (Belgium); Baeyens, Willy [Department of Analytical and Environmental Chemistry, Vrije Universiteit Brussel, Brussels (Belgium); Van Larebeke, Nicolas [Department of Analytical and Environmental Chemistry, Vrije Universiteit Brussel, Brussels (Belgium); Department of Radiotherapy and Experimental Cancerology, Ghent University, Ghent (Belgium); Boonen, Francis; Ooms, Daniëlla; Wevers, Mai; Jacobs, Griet [Flemish Institute for Technological Research (VITO), Mol (Belgium); Covaci, Adrian [Toxicological Centre, Department of Pharmaceutical Sciences, University of Antwerp, Antwerp (Belgium); Schettgen, Thomas [Department of Occupational and Social Medicine, RWTH Aachen University, Aachen (Germany); Schoeters, Greet [Flemish Institute for Technological Research (VITO), Mol (Belgium); Department of Biomedical Sciences, University of Antwerp, Antwerp (Belgium); University of Southern Denmark, Institute of Public Health, Department of Environmental Medicine, Odense (Denmark)

    2017-01-15

    Background: We investigated whether human environmental exposure to chemicals that are labeled as (potential) carcinogens leads to increased (oxidative) damage to DNA in adolescents. Material and methods: Six hundred 14–15-year-old youngsters were recruited all over Flanders (Belgium) and in two areas with important industrial activities. DNA damage was assessed by alkaline and formamidopyrimidine DNA glycosylase (Fpg) modified comet assays in peripheral blood cells and analysis of urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. Personal exposure to potentially carcinogenic compounds was measured in urine, namely: chromium, cadmium, nickel, 1-hydroxypyrene as a proxy for exposure to other carcinogenic polycyclic aromatic hydrocarbons (PAHs), t,t-muconic acid as a metabolite of benzene, 2,5-dichlorophenol (2,5-DCP), organophosphate pesticide metabolites, and di(2-ethylhexyl) phthalate (DEHP) metabolites. In blood, arsenic, polychlorinated biphenyl (PCB) congeners 118 and 156, hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT) and perfluorooctanoic acid (PFOA) were analyzed. Levels of methylmercury (MeHg) were measured in hair. Multiple linear regression models were used to establish exposure-response relationships. Results: Biomarkers of exposure to PAHs and urinary chromium were associated with higher levels of both 8-OHdG in urine and DNA damage detected by the alkaline comet assay. Concentrations of 8-OHdG in urine increased in relation with increasing concentrations of urinary t,t-muconic acid, cadmium, nickel, 2,5-DCP, and DEHP metabolites. Increased concentrations of PFOA in blood were associated with higher levels of DNA damage measured by the alkaline comet assay, whereas DDT was associated in the same direction with the Fpg-modified comet assay. Inverse associations were observed between blood arsenic, hair MeHg, PCB 156 and HCB, and urinary 8-OHdG. The latter exposure biomarkers were also associated with higher fish intake. Urinary nickel

  20. How many food additives are rodent carcinogens?

    Science.gov (United States)

    Johnson, F M

    2002-01-01

    One generally assumes that chemical agents added to foods are reasonably free of risks to human health, and practically everyone consumes some additives in his or her food daily throughout life. In the United States, the 1958 Food Additives Amendment to the Federal Food, Drug and Cosmetic Act of 1938 requires food manufacturers to demonstrate the safety of food additives to the Food and Drug Administration (FDA). The Amendment contains a provision that prohibits approval of an additive if it is found to cause cancer in humans or animals. In the present study, data from the National Toxicology Program rodent bioassay (NTPRB) were used to identify a sample of approximately 50 rodent-tested additives and other chemicals added to food that had been evaluated independently of the FDA/food industry. Surprisingly, the sample shows more than 40% of these food chemicals to be carcinogenic in one or more rodent groups. If this percentage is extrapolated to all substances added to food in the United States, it would imply that more than 1000 of such substances are potential rodent carcinogens. The NTP and FDA test guidelines use similar, though not necessarily identical, rodent test procedures, including near lifetime exposures to the maximum tolerated dose. The FDA specifies that test chemicals should be administered by the oral route. However, the oral route includes three methods of delivering chemicals, that is, mixed in the food or water or delivered by stomach tube (gavage). The NTP data show only 1 of 18 food chemicals mixed in the food are rodent carcinogens, but 16 of 23 gavage-administered food chemicals are carcinogenic to rodents. The distribution suggests that among orally delivered chemicals, those administered in the feed will more likely prove to be noncarcinogens than chemicals given by gavage. The rodent data also reveal that effects may vary according to dose and genotype, as well as by route of administration, to further complicate extrapolation to humans

  1. The multitude and diversity of environmental carcinogens

    International Nuclear Information System (INIS)

    Belpomme, D.; Irigaray, P.; Hardell, L.; Clapp, R.; Montagnier, L.; Epstein, S.; Sasco, A.J.

    2007-01-01

    We have recently proposed that lifestyle-related factors, screening and aging cannot fully account for the present overall growing incidence of cancer. In order to propose the concept that in addition to lifestyle related factors, exogenous environmental factors may play a more important role in carcinogenesis than it is expected, and may therefore account for the growing incidence of cancer, we overview herein environmental factors, rated as certainly or potentially carcinogenic by the International Agency for Research on Cancer (IARC). We thus analyze the carcinogenic effect of microorganisms (including viruses), radiations (including radioactivity, UV and pulsed electromagnetic fields) and xenochemicals. Chemicals related to environmental pollution appear to be of critical importance, since they can induce occupational cancers as well as other cancers. Of major concerns are: outdoor air pollution by carbon particles associated with polycyclic aromatic hydrocarbons; indoor air pollution by environmental tobacco smoke, formaldehyde and volatile organic compounds such as benzene and 1,3 butadiene, which may particularly affect children, and food pollution by food additives and by carcinogenic contaminants such as nitrates, pesticides, dioxins and other organochlorines. In addition, carcinogenic metals and metalloids, pharmaceutical medicines and cosmetics may be involved. Although the risk fraction attributable to environmental factors is still unknown, this long list of carcinogenic and especially mutagenic factors supports our working hypothesis according to which numerous cancers may in fact be caused by the recent modification of our environment

  2. Reaction of a chemotherapeutic agent, 6-mercaptopurine, with a direct-acting, electrophilic carcinogen, benzo[a]pyrene-7,8-diol 9,10-epoxide.

    Science.gov (United States)

    MacLeod, M C; Stewart, E; Daylong, A; Lew, L K; Evans, F E

    1991-01-01

    The chemotherapeutic agent 6-mercaptopurine (6-MP) has been shown to react covalently with the ultimate carcinogenic metabolite of benzo[a]pyrene, 7-r,8-t-dihydroxy-9-t,10-t-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE), in aqueous solution, forming a single adduct. NMR studies of the HPLC-purified product were consistent with its identification as 10(S)-(6'-mercaptopurinyl)-7,8,9-trihydroxy-7,8,9,10- tetrahydrobenzo[a]pyrene. Reaction kinetics were analyzed by using both HPLC separation of the products formed and a spectrophotometric assay for adduct formation. A simple model in which direct reaction between 6-MP and BPDE takes place without formation of a physical complex was found to adequately predict the dependence of product ratios on 6-MP concentration. Variations in the observed rate constant for this reaction with changes in temperature, pH, and buffer concentration were determined and compared to the effects of these variables on the observed rate constant for BPDE hydrolysis. In each case, the processes were affected quite differently, suggesting that different rate-determining steps are involved. The data suggest that the reaction mechanism involves SN2 attack of the anion of 6-MP, formed by ionization of the sulfhydryl group, on carbon 10 of BPDE, resulting in a trans-9,10 reaction product.

  3. The ultimate disposition of depleted uranium

    Energy Technology Data Exchange (ETDEWEB)

    1990-12-01

    Significant amounts of the depleted uranium (DU) created by past uranium enrichment activities have been sold, disposed of commercially, or utilized by defense programs. In recent years, however, the demand for DU has become quite small compared to quantities available, and within the US Department of Energy (DOE) there is concern for any risks and/or cost liabilities that might be associated with the ever-growing inventory of this material. As a result, Martin Marietta Energy Systems, Inc. (Energy Systems), was asked to review options and to develop a comprehensive plan for inventory management and the ultimate disposition of DU accumulated at the gaseous diffusion plants (GDPs). An Energy Systems task team, under the chairmanship of T. R. Lemons, was formed in late 1989 to provide advice and guidance for this task. This report reviews options and recommends actions and objectives in the management of working inventories of partially depleted feed (PDF) materials and for the ultimate disposition of fully depleted uranium (FDU). Actions that should be considered are as follows. (1) Inspect UF{sub 6} cylinders on a semiannual basis. (2) Upgrade cylinder maintenance and storage yards. (3) Convert FDU to U{sub 3}O{sub 8} for long-term storage or disposal. This will include provisions for partial recovery of costs to offset those associated with DU inventory management and the ultimate disposal of FDU. Another recommendation is to drop the term tails'' in favor of depleted uranium'' or DU'' because the tails'' label implies that it is waste.'' 13 refs.

  4. Carcinogenicity of the environmental pollutants cyclopenteno-(cd)pyrene and cyclopentano(cd)pyrene in mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Cavalieri, E.; Rogan, E.; Toth, B.; Munhall, A.

    1981-01-01

    Cyclopenteno(cd)pyrene (CPEP) is a widespread environmental pollutant. This hydrocarbon and its 3,4-dihydro derivative, cyclopentano(cd)pyrene (CPAP), were tested on skin in a two-stage initiation-promotion experiment in CD-1 mice and by repeated application in Swiss mice. The biological effect of CPEP and CPAP was compared to that of benzo(a)-pyrene (BP). Nine-week-old female CD-1 mice in groups of 30 were treated every other day over a 20-day period at mini-dose levels of 0.18, 0.06 and 0.02 mumol of CPEP or CPAP in acetone. One group was treated with BP at the low mini-dose level. Initiation was followed by twice weekly application of tetradecanoyl phorbol acetate for 40 weeks. In the second experiments, nine-week-old female Swiss mice in groups of 30 were treated at dose levels of 1.8, 0.6 and 0.2 mumol CPEP or CPAP in acetone twice weekly for 30 weeks. One group was treated with BP at the low dose. CPAP was virtually inactive in both studies. In the initiation-promotion experiment CPEP was inactive at the low dose level, whereas BP exhibited significant tumorigenicity. At the medium and high doses CPEP showed weak, but statistically insignificant, tumorigenic activity. Repeated application of CPEP at the high, medium and low doses resulted in tumor incidences of 23, 37 and 57%, respectively. This reverse dose-response may be due to the relatively high cytotoxicity of CPEP, BP, which was compared to CPEP at the low dose, elicited tumors in 100% of the mice. Most of the CPEP-induced neoplasms were malignant and some metastasized to lungs and lymph nodes. The inactivity of CPAP suggests the carcinogenicity of CPEP is probably due to formation of the ultimate metabolite CPEP 3,4-oxide. In view of the abundance of CPEP in environmental and occupational pollutants, its moderately potent carcinogenicity may represent a potential health hazard.

  5. Respiratory carcinogenicity assessment of soluble nickel compounds.

    Science.gov (United States)

    Oller, Adriana R

    2002-10-01

    The many chemical forms of nickel differ in physicochemical properties and biological effects. Health assessments for each main category of nickel species are needed. The carcinogenicity assessment of water-soluble nickel compounds has proven particularly difficult. Epidemiologic evidence indicates an association between inhalation exposures to nickel refinery dust containing soluble nickel compounds and increased risk of respiratory cancers. However, the nature of this association is unclear because of limitations of the exposure data, inconsistent results across cohorts, and the presence of mixed exposures to water-insoluble nickel compounds and other confounders that are known or suspected carcinogens. Moreover, well-conducted animal inhalation studies, where exposures were solely to soluble nickel, failed to demonstrate a carcinogenic potential. Similar negative results were seen in animal oral studies. A model exists that relates respiratory carcinogenic potential to the bioavailability of nickel ion at nuclear sites within respiratory target cells. This model helps reconcile human, animal, and mechanistic data for soluble nickel compounds. For inhalation exposures, the predicted lack of bioavailability of nickel ion at target sites suggests that water-soluble nickel compounds, by themselves, will not be complete human carcinogens. However, if inhaled at concentrations high enough to induce chronic lung inflammation, these compounds may enhance carcinogenic risks associated with inhalation exposure to other substances. Overall, the weight of evidence indicates that inhalation exposure to soluble nickel alone will not cause cancer; moreover, if exposures are kept below levels that cause chronic respiratory toxicity, any possible tumor-enhancing effects (particularly in smokers) would be avoided.

  6. Ultimately short ballistic vertical graphene Josephson junctions

    Science.gov (United States)

    Lee, Gil-Ho; Kim, Sol; Jhi, Seung-Hoon; Lee, Hu-Jong

    2015-01-01

    Much efforts have been made for the realization of hybrid Josephson junctions incorporating various materials for the fundamental studies of exotic physical phenomena as well as the applications to superconducting quantum devices. Nonetheless, the efforts have been hindered by the diffusive nature of the conducting channels and interfaces. To overcome the obstacles, we vertically sandwiched a cleaved graphene monoatomic layer as the normal-conducting spacer between superconducting electrodes. The atomically thin single-crystalline graphene layer serves as an ultimately short conducting channel, with highly transparent interfaces with superconductors. In particular, we show the strong Josephson coupling reaching the theoretical limit, the convex-shaped temperature dependence of the Josephson critical current and the exceptionally skewed phase dependence of the Josephson current; all demonstrate the bona fide short and ballistic Josephson nature. This vertical stacking scheme for extremely thin transparent spacers would open a new pathway for exploring the exotic coherence phenomena occurring on an atomic scale. PMID:25635386

  7. Ultimate-gradient accelerators physics and prospects

    CERN Document Server

    Skrinsky, Aleksander Nikolayevich

    1995-01-01

    As introduction, the needs and ways for ultimate acceleration gradients are discussed briefly. The Plasma Wake Field Acceleration is analized in the most important details. The structure of specific plasma oscillations and "high energy driver beam SP-plasma" interaction is presented, including computer simulation of the process. Some pratical ways to introduce the necessary mm-scale bunching in driver beam and to arrange sequential energy multiplication are dicussed. The influence of accelerating beam particle - plasma binary collisions is considered, also. As applications of PWFA, the use of proton super-colliders beams (LHC and Future SC) to drive the "multi particle types" accelerator, and the arrangements for the electron-positron TeV range collider are discussed.

  8. Ultimate load capacities of expansion anchor bolts

    International Nuclear Information System (INIS)

    Czarnecki, R.M.; Manrique, M.A.; Samaddar, S.K.

    1993-01-01

    A summary of available experimental expansion anchor bolt test data is presented. These data were collected as part of programs by the nuclear industry to address generic issues related to verification of seismic adequacy of equipment in nuclear power plants. Some of the data presented are suitable for use in seismic probabilistic risk assessments. For example, mean values of ultimate strength, along with their standard deviation and coefficients of variation, for a range of most typical expansion anchor bolt sizes are presented. Effects of interaction between shear and tension, edge distance, spacing, and cracking of the concrete are presented in a manner that is more suitable for use in deterministic evaluations. Related industry programs to derive anchor bolt capacities are briefly discussed. Recommendations for areas of further investigation are also presented

  9. Focused ion beam technology and ultimate applications

    International Nuclear Information System (INIS)

    Gierak, Jacques

    2009-01-01

    In this topical review, the potential of the focused ion beam (FIB) technology and ultimate applications are reviewed. After an introduction to the technology and to the operating principles of liquid metal ion sources (LMIS), of ion optics and instrument architectures, several applications are described and discussed. First, the application of FIB for microcircuit inspection, metrology and failure analysis is presented. Then, we introduce and illustrate some advanced patterning schemes we propose as next generation FIB processing examples. These patterning schemes are (i) local defect injection or smoothing in magnetic thin film direct patterning, (ii) functionalization of graphite substrates to guide organization of clusters, (iii) local and selective epitaxy of III–V semiconductor quantum dots and (iv) FIB patterned solid-state nanopores for biological molecules manipulation and analysis. We conclude this work by giving our vision of the future developments for FIB technology. (topical review)

  10. Transcending matter: physics and ultimate meaning.

    Science.gov (United States)

    Paulson, Steve; Frank, Adam; Kaiser, David; Maudlin, Tim; Natarajan, Priyamvada

    2015-12-01

    From the discovery of new galaxies and nearly undetectable dark energy to the quantum entanglement of particles across the universe, new findings in physics naturally elicit a sense of awe and wonder. For the founders of modern physics-from Einstein and Bohr to Heisenberg, Pauli, and Bohm-a fascination with deeper questions of meaning and ultimate reality led some of them to explore esoteric traditions and metaphysics. More recently, however, physicists have largely shunned such philosophical and spiritual associations. What can contemporary physics offer us in the quest to understand our place in the universe? Has physics in some ways become a religion unto itself that rejects the search for existential meaning? Discussion of these and related questions is presented in this paper. © 2015 New York Academy of Sciences.

  11. UHS, Ultimate Heat Sink Cooling Pond Analysis

    International Nuclear Information System (INIS)

    Codell, R.; Nuttle, W.K.

    1998-01-01

    1 - Description of program or function: Three programs model performance of an ultimate heat sink cooling pond. National Weather Service data is read and analyzed to predict periods of lowest cooling performance and highest evaporative loss. The data is compared to local site data for significant differences. Then the maximum pond temperature is predicted. Five programs model performance of an ultimate heat sink spray pond. The cooling performance, evaporative water loss, and drift water loss as a function of wind speed are estimated for a spray field. These estimates are used in conjunction with National Weather Service data to predict periods of lowest cooling performance and highest evaporative loss. This data is compared to local site data for significant differences. Then the maximum pond temperature is predicted. 2 - Method of solution: The transfer of heat and water vapor is modeled using an equilibrium temperature procedure for an UHS cooling pond. The UHS spray pond model considers heat, mass, and momentum transfer from a single water drop with the surrounding air, and modification of the surrounding air resulting from the heat, mass, and momentum transfer from many drops in different parts of a spray field. 3 - Restrictions on the complexity of the problem: The program SPRCO uses RANF, a uniform random number generator which is an intrinsic function on the CDC. All programs except COMET use the NAMELIST statement, which is non standard. Otherwise these programs conform to the ANSI Fortran 77 standard. The meteorological data scanning procedure requires tens of years of recorded data to be effective. The models and methods, provided as useful tool for UHS analyses of cooling ponds and spray ponds, are intended as guidelines only. Use of these methods does not automatically assure NRC approval, nor are they required procedures for nuclear-power-plant licensing

  12. Toxic Potential of Carcinogenic Polycyclic Aromatic Hydrocarbons ...

    African Journals Online (AJOL)

    Toxic Potential of Carcinogenic Polycyclic Aromatic Hydrocarbons (cPAHs) and Heavy Metal in Crude Oil from Gokana Area, Rivers State, Nigeria. ... Considerable caution should be applied in exploration, exposure and distribution of the crude oil through protected and well maintained pipelines to avoid the possible ...

  13. Mutagens and carcinogens in foods. Epidemiologic review.

    OpenAIRE

    Hislop, T. G.

    1993-01-01

    Evidence that diet contributes to the development of cancer is strengthening. This paper examines mutagens and carcinogens, such as naturally occurring substances, products of cooking and food processing, intentional and unintentional additives, and contaminants, found in foods. Such substances are present in minute quantities in the diets of average Canadians. Indication of health risk is largely limited to experimental laboratory evidence.

  14. Mutagens and carcinogens in foods. Epidemiologic review.

    Science.gov (United States)

    Hislop, T. G.

    1993-01-01

    Evidence that diet contributes to the development of cancer is strengthening. This paper examines mutagens and carcinogens, such as naturally occurring substances, products of cooking and food processing, intentional and unintentional additives, and contaminants, found in foods. Such substances are present in minute quantities in the diets of average Canadians. Indication of health risk is largely limited to experimental laboratory evidence. PMID:8499796

  15. Determination of carcinogenic polycyclic aromatic hydrocarbons in ...

    African Journals Online (AJOL)

    Determination of carcinogenic polycyclic aromatic hydrocarbons in air samples in Irbid, north Jordan. A Al-Gawadreh Sat, M.B. Gasim, A.R. Hassan, A Azid. Abstract. Air samples were collected at an urban site and a rural (BERQESH) site during February (2017) until March (2017) to determine concentrations of polycyclic ...

  16. Biomonitoring human exposure to environmental carcinogenic chemicals

    DEFF Research Database (Denmark)

    Farmer, P.B.; Sepai, O.; Lawrence, R.

    1996-01-01

    for detecting carcinogen-induced damage to DNA and proteins, and subsequent biological effects. These methods were validated with the occupational exposures, which showed evidence of DNA and/or protein and/or chromosome damage in workers in a coke oven plant, garage workers exposed to diesel exhaust and workers...

  17. Immunologic methods for monitoring carcinogen exposure

    Science.gov (United States)

    Santella, Regina M.; Perera, Frederica P.; Zhang, Yu J.; Chen, Chen J.; Young, Tie L.

    1993-03-01

    Immunologic methods have been developed for monitoring human exposure to environmental and occupational carcinogens. These methods involve the development of monoclonal and polyclonal antisera which specifically recognize the carcinogens themselves or their DNA or protein adducts. Antisera recognizing the DNA adducts of several polycyclic aromatic hydrocarbon diol epoxides have been used in competitive enzyme-linked immunosorbent assays to monitor adducts in tissue or blood samples. Elevated levels of DNA adducts have been seen in mononuclear cells of smokers and in total white blood cells of foundry and coke oven workers. Environmental exposure to PAH has been measured in individuals living in a highly polluted region of Poland. Antisera recognizing PAH-DNA adducts have also been used in immunohistochemical studies to monitor adducts in specific cells of biopsy samples. The DNA adducts of aflatoxin B1 have been monitored in liver tissue of hepatocellular carcinoma patients in Taiwan. Detectable adducts were seen in 50 - 70% of the patients suggesting that dietary exposure to this carcinogen may be a risk factor for cancer induction. Thus, immunoassays for monitoring exposure to carcinogens are an important tool in epidemiologic studies.

  18. Carcinogenic effects of radiation-introduction

    International Nuclear Information System (INIS)

    Setlow, R.B.

    1976-01-01

    The weight of experimental evidence reviewed indicates that UV damage to DNA, probably pyrimidine dimers, is the best molecular candidate for the initiating damage that leads to skin cancer. It is postulated that the carcinogenic action spectrum should be similar to the DNA action spectrum filtered through the upper layer of skin

  19. EPA's evaluation of the carcinogenic potential of glyphosate

    Science.gov (United States)

    Recently, several international agencies have evaluated the carcinogenic potential of glyphosate. In March 2015, the International Agency for Research on Cancer (IARC), a subdivision of the World Health Organization (WHO), determined that glyphosate was a probable carcinogen (gro...

  20. [Risk assessment of carcinogenic and non-carcinogenic effects in the use of food].

    Science.gov (United States)

    Frolova, O A; Karpova, M V

    2012-01-01

    Application of methodology for assessing the risk of diseases associated with consumption of contaminated foods, is aimed at predicting possible changes in the future and helps to create a framework for the prevention of negative effects on public health. The purpose of the study is assessment of health risks formed under the influence of chemical contaminants that pollute the food. Exponential average daily dose of receipt of chemicals in the body, non-carcinogenic and carcinogenic risks were calculated.

  1. Enhancements of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism and carcinogenic risk via NNK/arsenic interaction

    International Nuclear Information System (INIS)

    Lee, H.-L.; Chang, Louis W.; Wu, J.-P.; Ueng, Y.-F.; Tsai, M.-H.; Hsieh, Dennis Paul Hsientang; Lin Pinpin

    2008-01-01

    Epidemiological studies indicated an enhancement of cigarette smoke-induced carcinogenicity, including hepatocellular carcinoma, by arsenic. We believe that arsenic will enhance the expression of hepatic CYP2A enzyme and NNK metabolism (a cigarette smoke component), thus its metabolites, and carcinogenic DNA adducts. Male ICR mice were exposed to NNK (0.5 mg/mouse) and sodium arsenite (0, 10, or 20 mg/kg) daily via gavaging for 10 days and their urine was collected at day 10 for NNK metabolite analysis. Liver samples were also obtained for CYP2A enzyme and DNA adducts evaluations. Both the cyp2a4/5 mRNA levels and the CYP2A enzyme activity were significantly elevated in arsenic-treated mice liver. Furthermore, urinary NNK metabolites in NNK/arsenic co-treated mice also increased compared to those treated with NNK alone. Concomitantly, DNA adducts (N 7 -methylguanine and O 6 -methylguanine) were significantly elevated in the livers of mice co-treated with NNK and arsenic. Our findings provide clear evidence that arsenic increased NNK metabolism by up-regulation of CYP2A expression and activity leading to an increased NNK metabolism and DNA adducts (N 7 -methylguanine and O 6 -methylguanine). These findings suggest that in the presence of arsenic, NNK could induce greater DNA adducts formation in hepatic tissues resulting in higher carcinogenic potential

  2. Detection of carcinogen-DNA adducts by radioimmunoassay

    International Nuclear Information System (INIS)

    Poirier, M.C.; Yuspa, S.H.; Weinstein, I.B.; Blobstein, S.

    1977-01-01

    Covalent binding of carcinogen to nucleic acids is believed to be an essential component of the carcinogenic process, so it is desirable to have highly sensitive and specific methods for detecting such adducts in cells and tissues exposed to known and suspected carcinogens. A radioimmunoassay is here described capable of detecting nanogram amounts of DNA adducts resulting from the covalent binding of the carcinogen N-2-acetylaminofluorene and its activated N-acetoxy derivative. (author)

  3. Wall roughness induces asymptotic ultimate turbulence

    Science.gov (United States)

    Zhu, Xiaojue; Verschoof, Ruben A.; Bakhuis, Dennis; Huisman, Sander G.; Verzicco, Roberto; Sun, Chao; Lohse, Detlef

    2018-04-01

    Turbulence governs the transport of heat, mass and momentum on multiple scales. In real-world applications, wall-bounded turbulence typically involves surfaces that are rough; however, characterizing and understanding the effects of wall roughness on turbulence remains a challenge. Here, by combining extensive experiments and numerical simulations, we examine the paradigmatic Taylor-Couette system, which describes the closed flow between two independently rotating coaxial cylinders. We show how wall roughness greatly enhances the overall transport properties and the corresponding scaling exponents associated with wall-bounded turbulence. We reveal that if only one of the walls is rough, the bulk velocity is slaved to the rough side, due to the much stronger coupling to that wall by the detaching flow structures. If both walls are rough, the viscosity dependence is eliminated, giving rise to asymptotic ultimate turbulence—the upper limit of transport—the existence of which was predicted more than 50 years ago. In this limit, the scaling laws can be extrapolated to arbitrarily large Reynolds numbers.

  4. The ultimate challenge of cloacal exstrophy.

    Science.gov (United States)

    Schober, Justine M; Carmichael, Polly A; Hines, Melissa; Ransley, Philip G

    2002-01-01

    Our review addresses the various system abnormalities associated with cloacal exstrophy and revisits the question of gender assignment. Gender assignment decisions and psychological aspects of gender issues have become the "ultimate challenge." Exploration of gender identity, gender role behavior and sexual orientation has just begun. A comprehensive literature review was performed with all world literature regarding the current management of cloacal exstrophy. Research focused on management principles, outcomes and documentation of concurrent anomalies. We also describe original research evaluating gender identity in our own series of patients raised as girls to illustrate the challenge of treatment and augment the available literature, which is scant. Abnormalities of the vertebral column ranged from hemivertebra to myelomeningocele. With magnetic resonance imaging, the incidence of spinal dysraphism approached 100% and cord tethering was also more frequently recognized. For children with the short bowel syndrome, advances in antibiotic usage, and parenteral and enteral nutrition have increased the survival rate and reduced morbidity. A neurological component has been recognized for bladder function, bladder neck continence, lower extremity function and erectile capacity. Mitrofanoff-type reconstruction with bladder neck closure and continent catheterizable stoma dramatically increased continence. Diminutive or absent penis has been documented in 30% of males, and no documentation of paternity exists. The majority of females have bicornuate uterus. However, ovaries and tubes were generally normal. No reports of proven fertility exist. The strategy and timing of surgery relating to gender assignment remain controversial. A desperate need exists for research focusing on gender development and quality of life. Until that time, a cautious watchful approach may be most appropriate as our patients with cloacal exstrophy mature into adulthood.

  5. Developments in assessing carcinogenic risks from radiation

    International Nuclear Information System (INIS)

    Beebe, G.W.

    1984-01-01

    The papers in this volume have ranged widely over theoretical, experimental, and epidemiologic topics relating to radiation carcinogenesis. The multistage character of carcinogenesis, emphasis on the ease with which the initial event occurs in contrast to the infrequency of carcinogenic expression, the role of cell repair, and factors that may influence expression were major themes of the theoretical and experimental papers. The elegance of the cell transformation tool was illustrated in reviews of experimental work dealing with the exposure and environmental variables that influence radiation-induced transformation, among them the intracellular environment. Arguments were advanced for the view that more than one cell must be affected by radiation if a critical event is to occur. The relative congruence of carcinogens and clastogens was noted, and the suggestion made that the rules governing the induction of chromosomal aberrations by ionizing may apply to radiation carcinogenesis as well

  6. RADON AND CARCINOGENIC RISK IN MOSCOW

    Directory of Open Access Journals (Sweden)

    S. M. Golovanev

    2015-01-01

    Full Text Available Objective: comparative evaluation of carcinogenic risk inMoscowfrom radon in indoor and atmospheric pollutants.Materials and methods: the lung cancer incidence in Moscow; radiation-hygienic passport of the territory; .U.S. EPA estimated average age at all and radon induced deaths, years of life lost; Report of UNSCEAR 2006 and WHO handbook on indoor radon, 2009. Trend analysis of incidence; evaluation of the excess relative risk; assessment of ratio radon-induced population risk and published values оf total population carcinogenic risk from chemical carcinogens.Results: it is shown that the 304 cases of lung cancer per year (1. 85 10-3 on average from 2006 to 2011 (21280diseases for 70 years in addition to background level induced by radon; the differences in average trends of all lungcancer incidence in the districts can exceed 25%.Conclusion. The potential of risk reduction by measures of mitigation radon concentration exceeds 5 times the cost efficiency to reduce emissions from vehicles and can reduce cancer incidence, on average 236 cases per year; population risk 16520 cases over 70 years or save not less than 2832 person-years of life per year. The annual effect of reducing losses from not-survival of 12 years as a result of radon-induced lung cancer deaths exceeds 14160000 dollars. The evaluating of the carcinogenic risk from radon in accordance with the definition of population risk increases the predictive evaluation of the effectiveness of preventive measures more than twice.

  7. Respiratory carcinogenicity assessment of soluble nickel compounds.

    OpenAIRE

    Oller, Adriana R

    2002-01-01

    The many chemical forms of nickel differ in physicochemical properties and biological effects. Health assessments for each main category of nickel species are needed. The carcinogenicity assessment of water-soluble nickel compounds has proven particularly difficult. Epidemiologic evidence indicates an association between inhalation exposures to nickel refinery dust containing soluble nickel compounds and increased risk of respiratory cancers. However, the nature of this association is unclear...

  8. Recent developments in carcinogenic risk assessment

    International Nuclear Information System (INIS)

    Krewski, D.; Murdoch, D.; Withey, J.R.

    1989-01-01

    In this paper, recent developments in the quantitative assessment of carcinogenic risks based on toxicological and epidemiological data are reviewed. In particular, model-free approaches to low-dose risk assessment which involve only the assumption of low-dose linearity are considered. Measures of carcinogenic potency which avoid the need to extrapolate to low doses are also described. The allometric bases for converting risk estimates between species are then discussed. Pharmacokinetic models for determining the dose delivered to the target tissue are examined, and the implications of using such models in extrapolating between doses, of exposure, and species are examined. The application of these concepts in chemical and radiation carcinogenesis is illustrated by means of brief case studies of methylene chloride and Rn. Biologically motivated cancer models based on the initiation-promotion-progression theory of carcinogenesis are discussed and compared with the classical multistage model. The estimation of risks with time-dependent exposure patterns is considered, and conditions under which the use of a time-weighted average dose is appropriate are identified. Finally, the estimation of carcinogenic risks posed by exposure to complex mixtures is explored. 92 references

  9. Cytotoxic and mutagenic effects of specific carcinogen-DNA adducts in diploid human fibroblasts

    International Nuclear Information System (INIS)

    McCormick, J.J.; Maher, V.M.

    1985-01-01

    A comparison of the cytotoxicity and mutagenicity of a series of carcinogens in normal diploid human fibroblasts and in cells deficient in one or more DNA repair processes has provided insight into the specific DNA adduct(s) responsible for these biological effects. The carcinogens tested include ultraviolet radiation; reactive derivatives of structurally related aromatic amides; metabolites of benzo(a)pyrene; the simple alkylating agents N-methyl-N'-nitro-N-nitrosoguanidine and N-ethyl-N-nitrosourea; and aflatoxin B 1 dichloride, a model for the reactive 2,3-epoxide of aflatoxin B 1 . Exponentially growing cells were exposed to agents and assayed for mutations and cell killing. Cells deficient in repair of particular DNA adducts or lesions proved more sensitive to the agent causing those lesions than did normally repairing cells. Many of the carcinogens were compared for their mutagenic and/or cytotoxic effect, not only as a function of dose administered, but also as a function of the initial number of adducts or photoproducts induced in DNA and the number remaining at critical times posttreatment. The results demonstrated a high correlation between the number of DNA lesions remaining unexcised at the time the DNA was replicated and frequency of mutations induced. Comparative studies of the frequency of UV-induced transformation of normal and repair-deficient cells showed this also to be true for transformation

  10. Report on carcinogens monograph on cumene.

    Science.gov (United States)

    2013-09-01

    The National Toxicology Program conducted a cancer evaluation on cumene for possible listing in the Report on Carcinogens (RoC). The cancer evaluation is captured in the RoC monograph, which was peer reviewed in a public forum. The monograph consists of two components: (Part 1) the cancer evaluation, which reviews the relevant scientific information, assesses its quality, applies the RoC listing criteria to the scientific information, and provides the NTP recommendation for listing status for cumene in the RoC, and (Part 2) the substance profile proposed for the RoC, containing the NTP's listing status recommendation, a summary of the scientific evidence considered key to reaching that decision, and data on properties, use, production, exposure, and Federal regulations and guidelines to reduce exposure to cumene. This monograph provides an assessment of the available scientific information on cumene, including human exposure and properties, disposition and toxicokinetics, cancer studies in experimental animals, and studies of mechanisms and other related effects, including relevant toxicological effects, genetic toxicology, and mechanisms of carcinogenicity. From this assessment, the NTP recommended that cumene be listed as reasonably anticipated to be a human carcinogen in the RoC based on sufficient evidence from studies in experimental animals, which found that cumene exposure caused lung tumors in male and female mice and liver tumors in female mice. Several proposed mechanisms of carcinogenesis support the relevance to humans of the lung and liver tumors observed in experimental animals. Specifically, there is evidence that humans and experimental animals metabolize cumene through similar metabolic pathways. In addition, mutations of the K-ras oncogene and p53 tumor-suppressor gene observed in cumene-induced lung tumors in mice, along with altered expression of many other genes, resemble molecular alterations found in human lung and other cancers.

  11. Mequindox Induced Genotoxicity and Carcinogenicity in Mice

    Directory of Open Access Journals (Sweden)

    Qianying Liu

    2018-04-01

    Full Text Available Mequindox (MEQ, acting as an inhibitor of deoxyribonucleic acid (DNA synthesis, is a synthetic heterocyclic N-oxides. To investigate the potential carcinogenicity of MEQ, four groups of Kun-Ming (KM mice (50 mice/sex/group were fed with diets containing MEQ (0, 25, 55, and 110 mg/kg for one and a half years. The result showed adverse effects on body weights, feed consumption, hematology, serum chemistry, organ weights, relative organ weights, and incidence of tumors during most of the study period. Treatment-related changes in hematology, serum chemistry, relative weights and histopathological examinations revealed that the hematological system, liver, kidneys, and adrenal glands, as well as the developmental and reproductive system, were the main targets after MEQ administration. Additionally, MEQ significantly increased the frequency of micronucleated normochromatic erythrocytes in bone marrow cells of mice. Furthermore, MEQ increased the incidence of tumors, including mammary fibroadenoma, breast cancer, corticosuprarenaloma, haemangiomas, hepatocarcinoma, and pulmonary adenoma. Interestingly, the higher incidence of tumors was noted in M25 mg/kg group, the lowest dietary concentration tested, which was equivalent to approximately 2.25 and 1.72 mg/kg b.w./day in females and males, respectively. It was assumed that the lower toxicity might be a reason for its higher tumor incidence in M25 mg/kg group. This finding suggests a potential relationships among the dose, general toxicity and carcinogenicity in vivo, and further study is required to reveal this relationship. In conclusion, the present study demonstrates that MEQ is a genotoxic carcinogen in KM mice.

  12. Glyphosate rodent carcinogenicity bioassay expert panel review.

    Science.gov (United States)

    Williams, Gary M; Berry, Colin; Burns, Michele; de Camargo, Joao Lauro Viana; Greim, Helmut

    2016-09-01

    Glyphosate has been rigorously and extensively tested for carcinogenicity by administration to mice (five studies) and to rats (nine studies). Most authorities have concluded that the evidence does not indicate a cancer risk to humans. The International Agency for Research on Cancer (IARC), however, evaluated some of the available data and concluded that glyphosate probably is carcinogenic to humans. The expert panel convened by Intertek assessed the findings used by IARC, as well as the full body of evidence and found the following: (1) the renal neoplastic effects in males of one mouse study are not associated with glyphosate exposure, because they lack statistical significance, strength, consistency, specificity, lack a dose-response pattern, plausibility, and coherence; (2) the strength of association of liver hemangiosarcomas in a different mouse study is absent, lacking consistency, and a dose-response effect and having in high dose males only a significant incidence increase which is within the historical control range; (3) pancreatic islet-cell adenomas (non-significant incidence increase), in two studies of male SD rats did not progress to carcinomas and lacked a dose-response pattern (the highest incidence is in the low dose followed by the high dose); (4) in one of two studies, a non-significant positive trend in the incidence of hepatocellular adenomas in male rats did not lead to progression to carcinomas; (5) in one of two studies, the non-significant positive trend in the incidence of thyroid C-cell adenomas in female rats was not present and there was no progression of adenomas to carcinomas at the end of the study. Application of criteria for causality considerations to the above mentioned tumor types and given the overall weight-of-evidence (WoE), the expert panel concluded that glyphosate is not a carcinogen in laboratory animals.

  13. Carcinogen-induced damage to DNA

    International Nuclear Information System (INIS)

    Strauss, B.; Altamirano, M.; Bose, K.; Sklar, R.; Tatsumi, K.

    1979-01-01

    Human cells respond to carcinogen-induced damage in their DNA in at least two ways. The first response, excision repair, proceeds by at least three variations, depending on the nature of the damage. Nucleotide excision results in relatively large repair patches but few free DNA breaks, since the endonuclease step is limiting. Apurinic repair is characterized by the appearance of numerous breaks in the DNA and by short repair patches. The pathways behave as though they function independently. Lymphoic cells derived from a xeroderma pigmentosum complementation group C patient are deficient in their ability to perform nucleotide excision and also to excise 6 methoxyguanine adducts, but they are apurinic repair competent. Organisms may bypass damage in their DNA. Lymphoblastoid cells, including those derived from xeroderma pigmentosum treated with 3 H-anti-BPDE, can replicate their DNA at low doses of carcinogen. Unexcised 3 H is found in the light or parental strand of the resulting hybrid DNA when replication occurs in medium with BrdUrd. This observation indicates a bypass reaction occurring by a mechanism involving branch migration at DNA growing points. Branch migration in DNA preparations have been observed, but the evidence is that most occurs in BrdUrd-containing DNA during cell lysis. The measurement of the bifilarly substituted DNA resulting from branch migration is a convenient method of estimating the proportion of new synthesis remaining in the vicinity of the DNA growing point. Treatment with carcinogens or caffeine results in accumulation of DNA growing points accompanied by the synthesis of shortened pieces of daughter DNA

  14. Electrochemical methods for monitoring of environmental carcinogens.

    Science.gov (United States)

    Barek, J; Cvacka, J; Muck, A; Quaiserová, V; Zima, J

    2001-04-01

    The use of modern electroanalytical techniques, namely differential pulse polarography, differential pulse voltammetry on hanging mercury drop electrode or carbon paste electrode, adsorptive stripping voltammetry and high performance liquid chromatography with electrochemical detection for the determination of trace amounts of carcinogenic N-nitroso compounds, azo compounds, heterocyclic compounds, nitrated polycyclic aromatic hydrocarbons and aromatic and heterocyclic amines is discussed. Scope and limitations of these methods are described and some practical applications based on their combination with liquid-liquid or solid phase extraction are given.

  15. Indoor air-assessment: Indoor concentrations of environmental carcinogens

    International Nuclear Information System (INIS)

    Gold, K.W.; Naugle, D.F.; Berry, M.A.

    1991-01-01

    In the report, indoor concentration data are presented for the following general categories of air pollutants: radon-222, environmental tobacco smoke (ETS), asbestos, gas phase organic compounds, formaldehyde, polycyclic aromatic hydrocarbons (PAH), pesticides, and inorganic compounds. These pollutants are either known or suspect carcinogens (i.e., radon-222, asbestos) or more complex mixtures or classes of compounds which contain known or suspect carcinogens. Concentration data for individual carcinogenic compounds in complex mixtures are usually far from complete. The data presented for complex mixtures often include compounds which are not carcinogenic or for which data are insufficient to evaluate carcinogenicity. Their inclusion is justified, however, by the possibility that further work may show them to be carcinogens, cocarcinogens, initiators or promotors, or that they may be employed as markers (e.g., nicotine, acrolein) for the estimation of exposure to complex mixtures

  16. Carcinogenic 3-nitrobenzanthrone but not 2-nitrobenzanthrone is metabolised to an unusual mercapturic acid in rats.

    Science.gov (United States)

    Linhart, Igor; Mráz, Jaroslav; Hanzlíková, Iveta; Silhánková, Alexandra; Frantík, Emil; Himl, Michal

    2012-02-05

    3-Nitrobenzanthrone (3-NBA) is an extremely potent mutagen and suspect human carcinogen found in diesel exhaust. Its isomer 2-nitrobenzanthrone (2-NBA) has also been found in ambient air. These isomers differ in mutagenicity in Salmonella by 2-3 orders of magnitude. To identify their urinary metabolites and also to assess the assumed differences in their excretion, rats were dosed orally with 2mg/kg b.w. of either 2-NBA or 3-NBA. Their urine was collected for two consecutive days after dosage. Both LC-ESI-MS and GC-MS confirmed formation of the corresponding aminobenzanthrones (ABA). Excretion of these metabolites within the first day after dosing with 2- and 3-ABA amounted to 0.32±0.06 and 0.83±0.40% of the doses, respectively, while the excretion within the second day was by one order of magnitude lower. A novel mercapturic acid metabolite of 3-NBA was identified in urine by LC-ESI-MS as N-acetyl-S-(3-aminobenzanthron-2-yl)cysteine (3-ABA-MA) by comparison with the authentic standard. Its excretion amounted to 0.49±0.15 and 0.02±0.01% of dose within the first and second day after dosing, respectively. In contrast, no mercapturic acid was detected in the urine of rats dosed with 2-NBA. Observed difference in the mercapturic acid formation between 2- and 3-NBA is a new distinctive feature reflecting differences in the critical step of their metabolism, i.e., benzanthronylnitrenium ion formation that is intrinsically associated with biological activities of these two isomers. Moreover, 3-ABA-MA is a promising candidate biomarker of exposure to the carcinogenic 3-NBA. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  17. Direct ultimate disposal of spent fuel DEAB. Systems analysis. Ultimate disposal concepts. Final report. Main volume

    International Nuclear Information System (INIS)

    Wahl, A.

    1995-10-01

    The results elaborated under the project, systems analysis of mixed radwaste disposal concepts and systems analysis of ultimate disposal concepts, provide a comprehensive description and assessment of a radwaste repository, for heat generating wastes and for wastes with negligible heat generation, and thus represent the knowledge basis for forthcoming planning work for a repository in an abandoned salt mine. A fact to be considered is that temperature field calculations have shown that there is room for further optimization with regard to the mine layout. The following aspects have been analysed: (1) safety of operation; (2) technical feasibility and realisation and licensability of the concepts; (3) operational aspects; (4) varieties of utilization of the salt dome for the intended purpose (boreholes for waste emplacement, emplacement in galleries, multi-horizon systems); (5) long-term structural stability of the mine; (6) economic efficiency; (7) nuclear materials safeguards. (orig./HP) [de

  18. Carcinogenicity/tumour promotion by NDL PCB

    Energy Technology Data Exchange (ETDEWEB)

    Schrenk, D. [Kaiserslautern Univ. (Germany). Food Chemistry and Environmental Toxicology

    2004-09-15

    Polychlorinated biphenyls (PCBs) belong to the group of persistent environmental pollutants exhibiting neurotoxic, teratogenic and tumour-promoting effects in experimental animal models. PCB congeners can be divided into 'dioxinlike' and 'non-dioxinlike' congeners on the basis of their ability to act as aryl hydrocarbon receptor (AhR) agonists. Like the most toxic dioxin congener 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 'dioxinlike' PCBs bind to the AhR and show characteristic effects on the expression of AhR-regulated genes including the induction of cytochrome P450 (CYP) 1A1. On the other hand, 'non-dioxinlike' PCB congeners have a lower or no binding affinity to the AhR, but exhibit a 'phenobarbital-type' induction of CYP 2B1/2 activity. A carcinogenic potential of PCBs has been demonstrated with technical mixtures such as Aroclors or Clophens. In these studies the liver and the thyroid gland were found to be the principal target organs of PCB-mediated carcinogenesis in rodents. No studies have been published, however, on the carcinogenicity of individual congeners. In two-stage initiation-promotion protocols in rats, both technical mixtures and individual 'dioxinlike' and 'non-dioxinlike' congeners were reported to act as liver tumour promoters.

  19. Specificity of interaction between carcinogenic polynuclear aromatic hydrocarbons and nuclear proteins: widespread occurrence of a restricted pattern of histone-binding in intact cells

    International Nuclear Information System (INIS)

    MacLeod, M.C.; Pelling, J.C.; Slaga, T.J.; Nikbakht-Noghrei, P.A.; Mansfield, B.K.; Selkirk, J.K.

    1982-01-01

    Metabolic activation of benzo(a)pyrene [B(a)P] produces a number of potentially reactive metabolites. The endproducts of one metabolic pathway, 7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydro-B(a)P (BPDE) are responsible for essentially all DNA adduct formation in animal cells treated with B(a)P, and a particular stereoisomer, designated (+)-anti-BPDE is thought to be the ultimate carcinogenic derivative of B(a)P. In hamster embryo cell nuclei treated with (+)-anti-BPDE, two of the histones of the nucleosomal core, H3 and H2A, are covalently modified, while the remaining core histones, H4 and H2B, are essentially unmodified. All four purified core histones, however, serve as targets. 7,12-dimethylbenz(a)anthracene and 3-methylcholanthrene show the same pattern of histone binding in hamster embryo cells. Treatment of mouse embryo cells with [ 3 H]-BPDE results in covalent binding of the hydrocarbon to histones H3 and H2A among the many cellular targets, while histones H2B and H4 are not bound. Similar binding patterns are seen in mouse embryo cells, a permanent murine, fibroblastic cell line, and a human mammary epithelial cell line, T47D, treated with [ 3 H]B(a)P. Again, the histones are unevenly labeled, displaying the H3 and H2A pattern. Histone-binding in the human cells may also be mediated by BPDE. Similar BPDE binding patterns were observed in other murine and human cell lines and in primary cultures of murine epidermal epithelial cells. The restriction of histone H2B and H4 binding appears to be general when intact cultured cells are studied. This specificity was not observed in a mixed reconstituted system in which rat liver microsomes were used to activate B(a)P. This finding reinforces reservations concerning the use of microsomal systems to probe the interactions of carcinogens with macromolecules and the relationships of adduct formation with the processes of carcinogenesis

  20. Increased formation of carcinogenic PAH metabolites in fish promoted by nitrite

    Digital Repository Service at National Institute of Oceanography (India)

    Shailaja, M.S.; Rajamanickam, R.; Wahidullah, S.

    Nitrite (NO2−), a highly reactive chemical species, accumulates in coastal waters as a result of pollution with nitrogenous waste and/or an imbalance in the bacterial processes of nitrification and denitrification. The present study probed...

  1. Synthetic risks, risk potency, and carcinogen regulation.

    Science.gov (United States)

    Viscusi, W K; Hakes, J K

    1998-01-01

    This article analyzes a comprehensive sample of over 350 chemicals tested for carcinogenicity to assess the determinants of the probability of regulation. Controlling for differences in the risk potency and noncancer risks, synthetic chemicals have a significantly higher probability of regulation overall: this is due to the greater likelihood of U.S. Food and Drug Administration (FDA) regulation. Measures of risk potency increase the probability of regulation by the U.S. Environmental Protection Agency (EPA), have a somewhat weaker positive effect on regulation by the U.S. Occupational Safety and Health Administration (OSHA), and decrease the likelihood of regulation by the FDA. The overall regulatory pattern is one in which the FDA targets synthetic chemicals and chemicals that pose relatively minor cancer risk. The EPA particularly performed more sensibly than many critics have suggested.

  2. The mechanism of formation of (deoxy)guanosine adducts derived from peroxidase-catalyzed oxidation of the carcinogenic non-aminoazo dye 1-phenylazo-2-hydroxynaphthalene (SudanI)

    Czech Academy of Sciences Publication Activity Database

    Martínek, V.; Dračínský, Martin; Cvačka, Josef; Semanská, M.; Frei, E.; Stiborová, M.

    2009-01-01

    Roč. 276, Suppl. 1 (2009), s. 20-20 ISSN 1742-464X. [FEBS Congress /34/. 04.07.2009-09.07.2009, Praha] R&D Projects: GA AV ČR KJB400550903 Institutional research plan: CEZ:AV0Z40550506 Keywords : carcinogen * Sudan I metabolites * adducts Subject RIV: CC - Organic Chemistry

  3. Genotoxicity of Swimming Pool Water and Carcinogenicity of Drinking Water

    Science.gov (United States)

    Among the 11 disinfection by-products (DBPs) in drinking water that are regulated by the U.S. EPA, (a) 2 DBPs (chloroaceticacid and chlorite) are not carcinogenic-in either of2 species; (b) chlorite is not carcinogenic in 3 rodent assays and has never been tested for genotoxicity...

  4. Genotoxicity of Swimming Pool Water and Carcinogenicity of Drinking Water**

    Science.gov (United States)

    Among the 11 disinfection by-products (DBPs) in drinking water that are regulated by the U.S. EPA, (a) 2 DBPs (chloroaceticacid and chlorite) are not carcinogenic-in either of2 species; (b) chlorite is not carcinogenic in 3 rodent assays and has never been tested for genotoxicity...

  5. QSAR ligand dataset for modelling mutagenicity, genotoxicity, and rodent carcinogenicity

    Directory of Open Access Journals (Sweden)

    Davy Guan

    2018-04-01

    Full Text Available Five datasets were constructed from ligand and bioassay result data from the literature. These datasets include bioassay results from the Ames mutagenicity assay, Greenscreen GADD-45a-GFP assay, Syrian Hamster Embryo (SHE assay, and 2 year rat carcinogenicity assay results. These datasets provide information about chemical mutagenicity, genotoxicity and carcinogenicity.

  6. Workshop on problem areas associated with developing carcinogen guidelines

    Energy Technology Data Exchange (ETDEWEB)

    1984-06-01

    A workshop was conducted to discuss problem areas associated with developing carcinogen guidelines. Session topics included (1) definition of a carcinogen for regulatory purposes; (2) potency; (3) risk assessment; (4) uncertainties; (5) de minimis quantity; and (6) legal and regulatory issues. Separate abstracts have been prepared for individual papers. (ACR)

  7. Environmental carcinogenic agents and cancer prevention. Risk assessment and management

    International Nuclear Information System (INIS)

    Tsugane, Shoichiro

    2013-01-01

    Many agents in our environment have been established as being carcinogenic, and in most cases, the carcinogenic properties of these agents were identified because of high-dose occupational or accidental exposure. Risk characterization, taking into account the dose-response relationship, and exposure assessment are essential for risk assessment and subsequent cancer prevention. Based on scientific risk assessment, risk management should be conducted practically by considering the economic, social, political, and other technical issues and by balancing the risks and benefits. Asbestos and environmental tobacco smoke are typical examples of established carcinogenic agents in the general environment, contributing to low-dose exposure. Further epidemiological studies are required to investigate the carcinogenicity of low-dose exposure to known carcinogenic agents such as arsenic and cadmium through dietary intake, radiation via medical and natural exposure, and air pollution due to diesel exhaust. In contrast, occupational chemical exposure to 1,2-dichloropropane and/or dichloromethane, whose carcinogenicity had not been established, was suggested to cause cholangiocarcinoma among workers involved in offset color proof-printing only after a rare situation of high-dose exposure was unveiled. Continuous monitoring of unusual cancer occurrences in target populations such as workers in occupational and regional settings as well as exposure reduction to suspected carcinogenic agents to levels as low as reasonably achievable is essential for reducing the risk of cancer due to environmental carcinogens. (author)

  8. Ultimate Educational Aims, Overridingness, and Personal Well-Being

    Science.gov (United States)

    Haji, Ishtiyaque; Cuypers, Stefaan E.

    2011-01-01

    Discussion regarding education's aims, especially its ultimate aims, is a key topic in the philosophy of education. These aims or values play a pivotal role in regulating and structuring moral and other types of normative education. We outline two plausible strategies to identify and justify education's ultimate aims. The first associates these…

  9. Sensitivity analysis on ultimate strength of aluminium stiffened panels

    DEFF Research Database (Denmark)

    Rigo, P.; Sarghiuta, R.; Estefen, S.

    2003-01-01

    This paper presents the results of an extensive sensitivity analysis carried out by the Committee III.1 "Ultimate Strength" of ISSC?2003 in the framework of a benchmark on the ultimate strength of aluminium stiffened panels. Previously, different benchmarks were presented by ISSC committees on ul...

  10. Ultimate Lateral Capacity of Rigid Pile in c- φ Soil

    Science.gov (United States)

    Zhang, Wei-min

    2018-03-01

    To date no analytical solution of the pile ultimate lateral capacity for the general c- φ soil has been obtained. In the present study, a new dimensionless embedded ratio was proposed and the analytical solutions of ultimate lateral capacity and rotation center of rigid pile in c- φ soils were obtained. The results showed that both the dimensionless ultimate lateral capacity and dimensionless rotation center were the univariate functions of the embedded ratio. Also, the ultimate lateral capacity in the c- φ soil was the combination of the ultimate lateral capacity ( f c ) in the clay, and the ultimate lateral capacity ( f φ ) in the sand. Therefore, the Broms chart for clay, solution for clay ( φ=0) put forward by Poulos and Davis, solution for sand ( c=0) obtained by Petrasovits and Awad, and Kondner's ultimate bending moment were all proven to be the special cases of the general solution in the present study. A comparison of the field and laboratory tests in 93 cases showed that the average ratios of the theoretical values to the experimental value ranged from 0.85 to 1.15. Also, the theoretical values displayed a good agreement with the test values.

  11. An estimation of the carcinogenic risk associated with the intake of multiple relevant carcinogens found in meat and charcuterie products.

    Science.gov (United States)

    Hernández, Ángel Rodríguez; Boada, Luis D; Almeida-González, Maira; Mendoza, Zenaida; Ruiz-Suárez, Norberto; Valeron, Pilar F; Camacho, María; Zumbado, Manuel; Henríquez-Hernández, Luis A; Luzardo, Octavio P

    2015-05-01

    Numerous epidemiological studies have demonstrated a link between excessive meat consumption and the incidence of various cancers, especially colorectal cancer, and it has been suggested that environmental carcinogens present in meat might be related to the increased risk of cancer associated with this food. However, there are no studies evaluating the carcinogenic potential of meat in relation to its content of carcinogens. Our purpose was to emphasize the relevance of environmental carcinogens existing in meat as a determinant of the association between cancer and meat consumption. Because within Europe, Spain shows high consumption of meat and charcuterie, we performed this study focusing on Spanish population. Based on the preferences of consumers we acquired 100 samples of meat and charcuterie that reflect the variety available in the European market. We quantified in these samples the concentration of 33 chemicals with calculated carcinogenic potential (PAHs, organochlorine pesticides, and dioxin-like PCBs). The carcinogenic risk of these contaminants was assessed for each food using a risk ratio based on the current consumption of meat and charcuterie and the maximum tolerable intake of these foods depending on the level of contamination by the carcinogens they contain. Our results indicate that the current consumption of beef, pork, lamb, chicken, and "chorizo", represents a relevant carcinogenic risk for consumers (carcinogenic risk quotient between 1.33 and 13.98). In order to reduce carcinogenic risk, the study population should halve the monthly consumption of these foods, and also not to surpass the number of 5 servings of beef/pork/chicken (considered together). Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2015-01-01

    Algal blooms cause great damage to water quality and aquaculture. However, this study showed that dead algal cells and chlorophyll could accelerate the photo-transformation of benzo[a]pyrene (BaP), a ubiquitous and persistent pollutant with potently mutagenic and carcinogenic toxicities, under visible light irradiation. Chlorophyll was found to be the major active substance in dead algal cells, and generated a high level of singlet oxygen to catalyse the photo-transformation of BaP. According to various BaP metabolites formed, the degradation mechanism was proposed as that chlorophyll in dead algal cells photo-oxidized BaP to quinones via photocatalytic generation of singlet oxygen. The results provided a good insight into the role of chlorophyll in the photo-transformation of organic contaminants and could be a possible remediation strategy of organic pollutants in natural environment. PMID:26239357

  13. The tobacco carcinogen NNK is stereoselectively reduced by human pancreatic microsomes and cytosols.

    Science.gov (United States)

    Trushin, Neil; Leder, Gerhard; El-Bayoumy, Karam; Hoffmann, Dietrich; Beger, Hans G; Henne-Bruns, Doris; Ramadani, Marco; Prokopczyk, Bogdan

    2008-07-01

    Cigarette smoking increases the risk of cancer of the pancreas. The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is the only known environmental compound that induces pancreatic cancer in laboratory animals. Concentrations of NNK are significantly higher in the pancreatic juice of smokers than in that of nonsmokers. The chiral NNK metabolite, (R,S)-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is itself a potent pancreatic carcinogen in rats. The carcinogenicity of NNAL is related to its stereochemistry; (S)-NNAL is a more potent lung tumorigen in the A/J mouse than is (R)-NNAL. In this study, we determined the potential of the human pancreas to convert NNK into NNAL. Human pancreatic microsomes and cytosols were incubated with [5-(3)H]NNK, and the metabolic products were determined by high-performance liquid chromatography (HPLC). (S)-NNAL was the predominant isomer formed in all cytosolic incubations. In ten microsomal samples, NNAL was formed at an average rate of 3.8 +/- 1.6 pmol/mg/min; (R)-NNAL was the predominant isomer in this group. The average rate of NNAL formation in 18 other microsomal samples was significantly lower, 0.13 +/- 0.12 pmol/mg/min (p < 0.001); (S)-NNAL was the predominant isomer formed in this group. In human pancreatic tissues, there is intraindividual variability regarding the capacity for, and stereoselectivity of, carbonyl reduction of NNK.

  14. Impact of environmental exposures on the mutagenicity/carcinogenicity of heterocyclic amines

    Energy Technology Data Exchange (ETDEWEB)

    Felton, James S; Knize, Mark G; Bennett, L Michelle; Malfatti, Michael A; Colvin, Michael E; Kulp, Kristen S

    2004-05-20

    Carcinogenic heterocyclic amines are produced from overcooked foods and are highly mutagenic in most short-term test systems. One of the most abundant of these amines, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), induces breast, colon and prostate tumors in rats. Human dietary epidemiology studies suggest a strong correlation between either meat consumption or well-done muscle meat consumption and cancers of the colon, breast, stomach, lung and esophagus. For over 20 years our laboratory has helped define the human exposure to these dietary carcinogens. In this report we describe how various environmental exposures may modulate the risk from exposure to heterocyclic amines, especially PhIP. To assess the impact of foods on PhIP metabolism in humans, we developed an LC/MS/MS method to analyze the four major PhIP urinary metabolites following the consumption of a single portion of grilled chicken. Adding broccoli to the volunteers' diet altered the kinetics of PhIP metabolism. At the cellular level we have found that PhIP itself stimulates a significant estrogenic response in MCF-7 cells, but even more interestingly, co-incubation of the cells with herbal teas appear to enhance the response. Numerous environmental chemicals found in food or the atmosphere can impact the exposure, metabolism, and cell proliferation response of heterocyclic amines.

  15. Impact of environmental exposures on the mutagenicity/carcinogenicity of heterocyclic amines

    International Nuclear Information System (INIS)

    Felton, James S.; Knize, Mark G.; Bennett, L. Michelle; Malfatti, Michael A.; Colvin, Michael E.; Kulp, Kristen S.

    2004-01-01

    Carcinogenic heterocyclic amines are produced from overcooked foods and are highly mutagenic in most short-term test systems. One of the most abundant of these amines, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), induces breast, colon and prostate tumors in rats. Human dietary epidemiology studies suggest a strong correlation between either meat consumption or well-done muscle meat consumption and cancers of the colon, breast, stomach, lung and esophagus. For over 20 years our laboratory has helped define the human exposure to these dietary carcinogens. In this report we describe how various environmental exposures may modulate the risk from exposure to heterocyclic amines, especially PhIP. To assess the impact of foods on PhIP metabolism in humans, we developed an LC/MS/MS method to analyze the four major PhIP urinary metabolites following the consumption of a single portion of grilled chicken. Adding broccoli to the volunteers' diet altered the kinetics of PhIP metabolism. At the cellular level we have found that PhIP itself stimulates a significant estrogenic response in MCF-7 cells, but even more interestingly, co-incubation of the cells with herbal teas appear to enhance the response. Numerous environmental chemicals found in food or the atmosphere can impact the exposure, metabolism, and cell proliferation response of heterocyclic amines

  16. Carcinogen biomonitoring in human exposures and laboratory research: validation and application to human occupational exposures.

    Science.gov (United States)

    Talaska, Glenn; Maier, Andrew; Henn, Scott; Booth-Jones, Angela; Tsuneoka, Yutaka; Vermeulen, Roel; Schumann, Brenda L

    2002-08-05

    A multiple biomarker approach is required to integrate for metabolism, temporal response and exposure-response kinetics, biological relevance, and positive predictive value. Carcinogen DNA adduct analysis can be used in animal and in vitro studies to detect absorption permutations caused by mixture interactions, and to control metabolic variation when specific CYP450 genes (1A1 or 1A2) are knocked out. These enzymes are not critical to the metabolic activation of model Polycyclic Aromatic Compounds (PAC) and aromatic amines, respectively, as suggested by in vitro analysis. Several human studies have been carried out where multiple biomarkers have been measured. In a study of benzidine workers, the similarities in elimination kinetics between urinary metabolites and mutagenicity is likely responsible for a better correlation between these markers than to BZ-DNA adducts in exfoliated cells. In a study of rubber workers, the relationship between specific departments, urinary 1 HP and DNA adducts in exfoliated cells coincided with the historical urinary bladder cancer risk in these departments; the same relationship did not hold for urinary mutagenicity. In a study of automotive mechanics, biomarkers were used to monitor the effectiveness of exposure interventions. These data reinforce the notion that carcinogen biomarkers are useful to monitor exposure, but that a complementary approaches involving effect and perhaps susceptibility biomarkers is necessary to obtain the necessary information.

  17. Identifying occupational carcinogens: an update from the IARC Monographs.

    Science.gov (United States)

    Loomis, Dana; Guha, Neela; Hall, Amy L; Straif, Kurt

    2018-05-16

    The recognition of occupational carcinogens is important for primary prevention, compensation and surveillance of exposed workers, as well as identifying causes of cancer in the general population. This study updates previously published lists of known occupational carcinogens while providing additional information on cancer type, exposure scenarios and routes, and discussing trends in the identification of carcinogens over time. Data were extracted from International Agency for Research on Cancer (IARC) Monographs covering the years 1971-2017, using specific criteria to ensure occupational relevance and provide high confidence in the causality of observed exposure-disease associations. Selected agents were substances, mixtures or types of radiation classified in IARC Group 1 with 'sufficient evidence of carcinogenicity' in humans from studies of exposed workers and evidence of occupational exposure documented in the pertinent monograph. The number of known occupational carcinogens has increased over time: 47 agents were identified as known occupational carcinogens in 2017 compared with 28 in 2004. These estimates are conservative and likely underestimate the number of carcinogenic agents present in workplaces. Exposure to these agents causes a wide range of cancers; cancers of the lung and other respiratory sites, followed by skin, account for the largest proportion. The dominant routes of exposure are inhalation and dermal contact. Important progress has been made in identifying occupational carcinogens; nevertheless, there is an ongoing need for research on the causes of work-related cancer. Most workplace exposures have not been evaluated for their carcinogenic potential due to inadequate epidemiologic evidence and a paucity of quantitative exposure data. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Identification and monitoring of non-radiological carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Chuaqui, C A; Petkau, A; Greenstock, C L; Brown, C P [Atomic Energy of Canada Ltd., Pinawa, MB (Canada). Whiteshell Labs.

    1995-09-01

    This study examines the feasibility of identifying and monitoring occupational exposures to non-radiological carcinogens in the workplace at Canadian nuclear establishments (Whiteshell Laboratories, Pickering Nuclear Generating Station, Cameco Limited and Canadian General Electric Company Limited). Recent epidemiological studies recommended that potential confounding factors of a non-radiological nature be identified and analyzed, particularly non-radiological carcinogens that may be present in the workplace at nuclear facilities. The feasibility of identifying and measuring occupational exposures to non-radiological carcinogens in Canadian nuclear facilities is examined. Also, the report describes the problem of chemical carcinogens and the mechanisms involved in chemical carcinogenesis; the epidemiology related to the problem, followed by a description of the analytical aspects of detection, monitoring and analysis of carcinogens, as well as a discussion on the regulatory aspects and the regulations in place; and the findings, recommendations and concluding remarks of this study. Several problem areas became apparent as the study proceeded. For example, the classification of a chemical as a human carcinogen is a difficult problem, as is its adequate monitoring and analysis. This situation reflects, in turn, the regulatory aspects in the workplace. A list of chemical carcinogens used industrially at the four Canadian nuclear facilities has been identified. The list includes arsenic, asbestos, benzene, cadmium, beryllium, nickel, polychlorinated biphenyls, lead and trichloroethylene. Several recommendations are made in relation to the need for practical and efficient monitoring methods for chemical carcinogens, the definition of radiation and chemical dose equivalencies, and the classification of human chemical carcinogens, as well as their disposal. (author). 122 refs., 8 tabs., 6 figs.

  19. Identification and monitoring of non-radiological carcinogens

    International Nuclear Information System (INIS)

    Chuaqui, C.A.; Petkau, A.; Greenstock, C.L.; Brown, C.P.

    1995-09-01

    This study examines the feasibility of identifying and monitoring occupational exposures to non-radiological carcinogens in the workplace at Canadian nuclear establishments (Whiteshell Laboratories, Pickering Nuclear Generating Station, Cameco Limited and Canadian General Electric Company Limited). Recent epidemiological studies recommended that potential confounding factors of a non-radiological nature be identified and analyzed, particularly non-radiological carcinogens that may be present in the workplace at nuclear facilities. The feasibility of identifying and measuring occupational exposures to non-radiological carcinogens in Canadian nuclear facilities is examined. Also, the report describes the problem of chemical carcinogens and the mechanisms involved in chemical carcinogenesis; the epidemiology related to the problem, followed by a description of the analytical aspects of detection, monitoring and analysis of carcinogens, as well as a discussion on the regulatory aspects and the regulations in place; and the findings, recommendations and concluding remarks of this study. Several problem areas became apparent as the study proceeded. For example, the classification of a chemical as a human carcinogen is a difficult problem, as is its adequate monitoring and analysis. This situation reflects, in turn, the regulatory aspects in the workplace. A list of chemical carcinogens used industrially at the four Canadian nuclear facilities has been identified. The list includes arsenic, asbestos, benzene, cadmium, beryllium, nickel, polychlorinated biphenyls, lead and trichloroethylene. Several recommendations are made in relation to the need for practical and efficient monitoring methods for chemical carcinogens, the definition of radiation and chemical dose equivalencies, and the classification of human chemical carcinogens, as well as their disposal. (author). 122 refs., 8 tabs., 6 figs

  20. Influence of initial imperfections on ultimate strength of spherical shells

    Directory of Open Access Journals (Sweden)

    Chang-Li Yu

    2017-09-01

    Full Text Available Comprehensive consideration regarding influence mechanisms of initial imperfections on ultimate strength of spherical shells is taken to satisfy requirement of deep-sea structural design. The feasibility of innovative numerical procedure that combines welding simulation and non-linear buckling analysis is verified by a good agreement to experimental and theoretical results. Spherical shells with a series of wall thicknesses to radius ratios are studied. Residual stress and deformations from welding process are investigated separately. Variant influence mechanisms are discovered. Residual stress is demonstrated to be influential to stress field and buckling behavior but not to the ultimate strength. Deformations are proved to have a significant impact on ultimate strength. When central angles are less than critical value, concave magnitudes reduce ultimate strengths linearly. However, deformations with central angles above critical value are of much greater harm. Less imperfection susceptibility is found in spherical shells with larger wall thicknesses to radius ratios.

  1. Ultimate guide to YouTube for business

    CERN Document Server

    2018-01-01

    Ultimate Guide to YouTube for Business helps small business owners create marketing videos to help promote their products, share their story, build a community around their brand without spending a fortune-all the while making money.

  2. Studies on carcinogenic effect of tritiated water

    International Nuclear Information System (INIS)

    Zou Shuai; Wang Hui; Li Maohe; Lin Suqin

    1994-09-01

    Studies on carcinogenic effect of tritiated water is introduced in two parts. The first part is an in vitro study in which CHL-1 cells were exposed to tritiated water (9.25 x 10 5 ∼ 3.5 x 10 6 Bq/ml) for 24 ∼ 96 h and the accumulated dose was from 0.055 to 0.88 Gy. In order to estimate RBE of tritium for malignant transformation in CHL-1 cells, the induction of malignant transformation in CHL-1 cells by exposure to gamma rays of 137 Cs was tested. Based on the transformation rates, the RBE of tritium for malignant transformation in CHL-1 cells was estimated to be 1.6. The second part is an in vivo study. In the study, rats were fed with tritiated water (2.22 x 10 5 and 1.11 x 10 5 Bq/ml) for 1.5 a. Rats in control group were fed with tap water. Results showed that in the statistics, the differences in the total tumor incidence and malignant tumor incidence between high and low dose rate groups and control groups were remarkably significant

  3. Environmental carcinogens and prophylaxis of malignant tumors

    Energy Technology Data Exchange (ETDEWEB)

    Shabad, L M

    1977-01-01

    A short history of a relatively new branch of cancer research, hygienic oncology, is reviewed. Occupational skin tumors (papillomas and even squamous-cell carcinoma) are described not only among chimney-sweepers, but also among the workers of petroleum refineries. Of 512 workers who had prolonged exposure to various petroleum products, 53.2% developed skin carcinoma. Occupational malignant tumors of the respiratory tract are observed among the workers of nickel industries. Workers who experienced prolonged exposure to asbestos had an increased incidence of lung and stomach cancer. To prevent occuptional cancer of the urinary bladder, such carcinogens as 2-napthylamine, 3,3-dichlorobenzidine, 3,3-dioxybenzidine, and para-amino-azobenzene were banned. Environmental pollution with the products of incomplete fuel combustion, especially with polycyclic aromatic carbohydrates constitutes a hazard to the urban population. The level of benzopyrene (BP) in soil samples taken in different localities averaged 5 microg/kg. Legislatively approved permissible concentrations of BP in the air are 0.1 microg/100 cubic meters, and in the water 0.005 microg/liter. 23 references.

  4. Dehydropyrrolizidine Alkaloid Toxicity, Cytotoxicity, and Carcinogenicity

    Directory of Open Access Journals (Sweden)

    Bryan L. Stegelmeier

    2016-11-01

    Full Text Available Dehydropyrrolizidine alkaloid (DHPA-producing plants have a worldwide distribution amongst flowering plants and commonly cause poisoning of livestock, wildlife, and humans. Previous work has produced considerable understanding of DHPA metabolism, toxicity, species susceptibility, conditions, and routes of exposure, and pathogenesis of acute poisoning. Intoxication is generally caused by contaminated grains, feed, flour, and breads that result in acute, high-dose, short-duration poisoning. Acute poisoning produces hepatic necrosis that is usually confirmed histologically, epidemiologically, and chemically. Less is known about chronic poisoning that may result when plant populations are sporadic, used as tisanes or herbal preparations, or when DHPAs contaminate milk, honey, pollen, or other animal-derived products. Such subclinical exposures may contribute to the development of chronic disease in humans or may be cumulative and probably slowly progress until liver failure. Recent work using rodent models suggest increased neoplastic incidence even with very low DHPA doses of short durations. These concerns have moved some governments to prohibit or limit human exposure to DHPAs. The purpose of this review is to summarize some recent DHPA research, including in vitro and in vivo DHPA toxicity and carcinogenicity reports, and the implications of these findings with respect to diagnosis and prognosis for human and animal health.

  5. Ultimate Opening Combined with Area Stability Applied to Urban Scenes

    OpenAIRE

    Marcotegui , Beatriz; Serna , Andrés; Hernández , Jorge

    2017-01-01

    International audience; This paper explores the use of ultimate opening in urban analysis context. It demonstrates the efficiency of this approach for street level elevation images, derived from 3D point clouds acquired by terrestrial mobile mapping systems. An area-stability term is introduced in the residual definition, reducing the over-segmentation of the vegetation while preserving small significant regions. We compare two possible combinations of the Ultimate Opening and the Area Stabil...

  6. Direct ultimate disposal - state of investigations and prospects

    International Nuclear Information System (INIS)

    Gasterstaedt, N.

    1991-01-01

    Based on a decision adopted by the Prime Ministers on 25/10/90, the principles governing preventive waste management of nuclear power plants are reviewed. Increasing importance is attached to the direct ultimate disposal alternative. The legal and political framework, the technology involved, the state of developments, future activities under the R and D programme as well as a cost estimate of direct ultimate disposal are presented. (orig.) [de

  7. Assessment and characterization of radioactive waste for ultimate storage

    International Nuclear Information System (INIS)

    Brennecke, P.; Warnecke, E.

    1986-01-01

    The waste specifications determined from site safety analyses define the requirements to be met by waste forms for ultimate storage. Product quality control is the process step ensuring compliance with the conditions to be met for ultimate storage. For this purpose, radionuclide inventory, fixation method, container type, waste form and quantity, and type of waste are the most significant items on the checking list. (DG) [de

  8. Transportable hyperpolarized metabolites

    Science.gov (United States)

    Ji, Xiao; Bornet, Aurélien; Vuichoud, Basile; Milani, Jonas; Gajan, David; Rossini, Aaron J.; Emsley, Lyndon; Bodenhausen, Geoffrey; Jannin, Sami

    2017-01-01

    Nuclear spin hyperpolarization of 13C-labelled metabolites by dissolution dynamic nuclear polarization can enhance the NMR signals of metabolites by several orders of magnitude, which has enabled in vivo metabolic imaging by MRI. However, because of the short lifetime of the hyperpolarized magnetization (typically <1 min), the polarization process must be carried out close to the point of use. Here we introduce a concept that markedly extends hyperpolarization lifetimes and enables the transportation of hyperpolarized metabolites. The hyperpolarized sample can thus be removed from the polarizer and stored or transported for use at remote MRI or NMR sites. We show that hyperpolarization in alanine and glycine survives 16 h storage and transport, maintaining overall polarization enhancements of up to three orders of magnitude. PMID:28072398

  9. Foetal exposure to food and environmental carcinogens in human beings.

    Science.gov (United States)

    Myöhänen, Kirsi; Vähäkangas, Kirsi

    2012-02-01

    Exposure to many different chemicals during pregnancy through maternal circulation is possible. Transplacental transfer of xenobiotics can be demonstrated using human placental perfusion. Also, placental perfusion can give information about the placental kinetics as well as metabolism and accumulation in the placenta because it retains the tissue structure and function. Although human placental perfusion has been used extensively to study the transplacental transfer of drugs, the information on food and environmental carcinogens is much more limited. This review deals with the foetal exposure to food and environmental carcinogens in human beings. In particular, human transplacental transfer of the food carcinogens such as acrylamide, glycidamide and nitrosodimethylamine are in focus. Because these carcinogens are genotoxic, the functional capacity of human placenta to induce DNA adduct formation or metabolize these above mentioned CYP2E1 substrates is of interest in this context. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

  10. Carcinogenicity tests of certain environmental and industrial chemicals

    International Nuclear Information System (INIS)

    Weisburger, E.K.; Ulland, B.M.; Nam, J.; Gart, J.J.; Weisburger, J.H.

    1981-01-01

    Fourteen chemicals of varied uses were tested for carcinogenicity by oral administration in male and female Charles River CD rats. Under the conditions of the tests, propane sultone, propylene imine, and ethylenethiourea, in addition to the positive control N-2-fluorenylacetamide, were carcinogenic. Avadex, bis(2-chloroethyl) ether, the potassium salt of bis(2-hydroxyethyl) dithiocarbamic acid, ethylene carbonate, and semicarbazide hydrochloride were not carcinogenic under the test conditions. Dithiooxamide, glycerol alpha-monochlorohydrin, and thiosemicarbazide gave somewhat ambiguous results, though administered at high enough dose levels to be toxic. An inadequate number of animals survived treatments with sodium azide, sodium bisulfide, and vinylene carbonate, or the animals may not have received sufficiently high doses of the test chemicals to provide maximum test sensitivity. However, there were no indications that these three chemicals were carcinogenic under the test conditions

  11. Ultimate - a new generation of gasoline and diesel fuels; Ultimate - eine neue Generation von Otto- und Dieselkraftstoffen

    Energy Technology Data Exchange (ETDEWEB)

    Strempel, G. [Aral Forschung/Global Fuels Technology, Bochum (Germany); Beckwith, P. [BP Fuels Management Group, Pangbourne (United Kingdom); Froehling, J. [Aral Forschung, Bochum (Germany). Labor/Analytik; Baron, U. [Aral Forschung, Bochum (Germany). Motor- und Fahrzeuglaboratorium; Sauermann, P.; Balfanz, U. [Aral Forschung, Bochum (Germany). Produktentwicklung; Doermer, W. [Aral Forschung, Bochum (Germany). Produktqualitaet

    2005-06-01

    With the launch of Ultimate 100 gasoline and Ultimate Diesel, motorists in Germany now have the opportunity to choose new advanced performance fuels designed to get the very best from their engines. This article gives details of the technical development behind these fuels, their wide range of benefits, and how it is possible to manufacture fuels which meet the considerable technical challenge of achieving both more performance and less pollution. (orig.)

  12. THE ULTIMATE STATE CONCEPT APPLIED TO TUNNEL SUPPORT

    Directory of Open Access Journals (Sweden)

    Mladen Hudec

    2000-12-01

    Full Text Available The most questionable are the values of pressures between rock and support resulting from common deformations on the contact area between rock and support. Therefore the modelling and design of the tunnel support is not reliable, if it is based on active rock pressure resulting from this common deformations. The inversion of the design procedure is proposed. Instead of the active extreme pressure of the rock on support, the influence of ultimate reaction of the support on the rock has to be analysed. This procedure can be performed using the ultimate load principle, as proposed by Eurocodc 7 (Geotechnies. Normally, the rock has the tendency to increase the common conver¬gence until the support reaches its ultimate state. So, loading of profile boundary with the ultimate possible reaction of the support is very plausible. The reactive support pressures have to be probable and itself in equilibrium. The ultimate reactive load has to be reduced by Euro-code safety factor for structural elements and applied on the rock with given properties, or alternatively (as proposed by Eurocode 7 the soil or rock properties have to be diminished and calculated with full ultimate support pressures. If the rock with given (or proposed pro¬perties and loaded with ultimate reactive pressures resulting from supposed support, satisfy its failure criterion, then is the compound system support-rock verificatcd. By this procedure, the number of relevant material properties is reduce to the primary stress ratio and the constants defining the failure criterion. The verification can be performed by any of numerical methods, but we prefer here used boundary elements method (the paper is published in Croatian.

  13. Liver fatty acid binding protein is the mitosis-associated polypeptide target of a carcinogen in rat hepatocytes

    International Nuclear Information System (INIS)

    Bassuk, J.A.; Tsichlis, P.N.; Sorof, S.

    1987-01-01

    Hepatocytes in normal rat liver were found previously to contain a cytoplasmic 14,000-dalton polypeptide (p14) that is associated with mitosis and is the principal early covalent target of activated metabolites of the carcinogen N-2-fluorenylacetamide (2-acetylaminofluorene). The level of immunohistochemically detected p14 was low when growth activity of hepatocytes was low, was markedly elevated during mitosis in normal and regenerating livers, but was very high throughout interphase during proliferation of hyperplastic and malignant hepatocytes induced in rat liver by a carcinogen (N-2-fluorenylacetamide or 3'-methyl-4-dimethylaminoazobenzene). The authors report here that p14 is the liver fatty acid binding protein. The nucleotide sequence of p14 cDNA clones, isolated by screening a rat liver cDNA library in bacteriophage λgt11 using p14 antiserum, was completely identical to part of the sequence reported for liver fatty acid binding protein. Furthermore, the two proteins shared the following properties: size of mRNA, amino acid composition, molecular size according to NaDodSO 4 gel electrophoresis, and electrophoretic mobilities in a Triton X-100/acetic acid/urea gel. The two polypeptides bound oleic acid similarly. Finally, identical elevations of cytoplasmic immunostain were detected specifically in mitotic hepatocytes with either antiserum. The collected findings are suggestive that liver fatty acid binding protein may carry ligands that promote hepatocyte division and may transport certain activated chemical carcinogens

  14. Relative potency estimation for synthetic petroleum skin carcinogens.

    OpenAIRE

    Holland, J M; Wolf, D A; Clark, B R

    1981-01-01

    A procedure for quantitative analysis of skin carcinogenesis data, for the purpose of establishing carcinogenic potency, has been applied to observations obtained from C3H mice exposed continuously to synthetic and natural petroleums. The importance of total polynuclear aromatic (PNA) content to the skin carcinogenic activity of the crude materials was also examined. Of three synthetic petroleums evaluated, all were shown capable of inducing skin neoplasms within a two-year exposure period. U...

  15. Hexavalent chrome: threshold concept for carcinogenicity.

    Science.gov (United States)

    Jones, R E

    1990-03-01

    Certain hexavalent chromium (Cr6+) compounds when administered via inhalation at high doses have the potential to induce lung tumors in humans and experimental animals. Trivalent chromium (Cr3+) is an essential human and animal nutrient at levels of 50 to 200 micrograms/day. Recent data have shown that the human body is able to reduce Cr6+ to Cr3+. This reduction occurs in bodily fluids such as gastric juice, epithelial lining fluid of the respiratory tract, blood, and other fluids. Secondary reduction occurs at the cellular level by the cytosol, mitochondria, and microsomes. Thus, at low levels of exposure hexavalent chromium ions are reduced before the 6+ ions can interact with DNA unless the dose is sufficient to overwhelm the body's reduction capacity. This paper summarizes the available data concerning the reducing ability of the body and formulates the steps in the mechanism of cancer induction. These steps include: (1) only certain Cr6+ compounds have the capacity to interact with cellular components; (2) Cr6+ is reduced by body fluids and excess Cr6+ enters the cell (Cr3+ is poorly absorbed across membranes); (3) cellular organelles and the cytoplasm reduce Cr6+ to Cr3+; (4) excess Cr6+ can enter the nucleus; (5) Cr6+ reduction through 5+ and 4+ to 3+ has a potential to interact with the DNA molecule; and (6) if unrepaired, this DNA damage can lead to cancer induction. On the basis of current evidence Cr6+ has a threshold for carcinogenic potential in humans that is greater than the current TLV.

  16. Carcinogenic and mutagenic properties of chemicals in drinking water

    Energy Technology Data Exchange (ETDEWEB)

    Bull, R J

    1985-12-01

    Isolated cases of careless handling of industrial and domestic waste has lead to a wide variety of dangerous chemicals being inadvertently introduced into drinking water. However, chemicals with established carcinogenic and mutagenic properties that occur with a high frequency and in multiple locations are limited in number. To date, the chief offenders have been chemicals of relatively low carcinogenic potency. Some of the more common chemicals are formed as by-products of disinfection. The latter process is generally regarded as essential to the production of a ''microbiologically safe'' drinking water. Consequently, any reductions in what may be a relatively small carcinogenic risk must be balanced against a potential for a higher frequency of waterborne infectious disease. The results of recent toxicological investigations will be reviewed to place the potential carcinogenic and mutagenic hazards frequently associated with drinking water into perspective. First, evidence for the carcinogenicity of certain volatile organic compounds such as trichloroethylene, tetrachloroethylene and carbon tetrachloride is considered. Second, the carcinogenic activity that can be ascribed to various by-products of chlorination is reviewed in some detail. Finally, recent evidence that other chemicals derived from the treatment and distribution of drinking water is highlighted as an area requiring move systematic attention. 72 references.

  17. Is ionizing radiation regulated more stringently than chemical carcinogens

    International Nuclear Information System (INIS)

    Travis, C.C.; Pack, S.R.; Hattemer-Frey, H.A.

    1989-01-01

    It is widely believed that United States government agencies regulate exposure to ionizing radiation more stringently than exposure to chemical carcinogens. It is difficult to verify this perception, however, because chemical carcinogens and ionizing radiation are regulated using vastly different strategies. Chemical carcinogens are generally regulated individually. Regulators consider the risk of exposure to one chemical rather than the cumulative radiation exposure from all sources. Moreover, standards for chemical carcinogens are generally set in terms of quantities released or resultant environmental concentrations, while standards for ionizing radiation are set in terms of dose to the human body. Since chemicals and ionizing radiation cannot be compared on the basis of equal dose to the exposed individual, standards regulating chemicals and ionizing radiation cannot be compared directly. It is feasible, however, to compare the two sets of standards on the basis of equal risk to the exposed individual, assuming that standards for chemicals and ionizing radiation are equivalent if estimated risk levels are equitable. This paper compares risk levels associated with current standards for ionizing radiation and chemical carcinogens. The authors do not attempt to determine whether either type of risk is regulated too stringently or not stringently enough but endeavor only to ascertain if ionizing radiation is actually regulated more strictly than chemical carcinogens

  18. Relevance of urinary 3-hydroxybenzo(a)pyrene and 1-hydroxypyrene to assess exposure to carcinogenic polycyclic aromatic hydrocarbon mixtures in metallurgy workers.

    Science.gov (United States)

    Barbeau, Damien; Persoons, Renaud; Marques, Marie; Hervé, Claire; Laffitte-Rigaud, Gilbert; Maitre, Anne

    2014-06-01

    In metallurgy, workers are exposed to mixtures of polycyclic aromatic hydrocarbons (PAHs) in which some compounds are carcinogenic. Biomonitoring of PAH exposure has been performed by measuring urinary 1-hydroxypyrene (1-OHP), a metabolite of pyrene which is not carcinogenic. This study investigated the use of 3-hydroxybenzo(a)pyrene (3-OHBaP), a metabolite of benzo(a)pyrene (BaP) which is the main carcinogenic component in PAHs, to improve carcinogen exposure assessment. We included 129 metallurgy workers routinely exposed to PAHs during working hours. Urinary samples were collected at three sampling times at the beginning and at the end of the working week for 1-OHP and 3-OHBaP analyses. Workers in anode production showed greater exposure to both biomarkers than those in cathode or silicon production, with respectively, 71, 40, and 30% of 3-OHBaP concentrations exceeding the value of 0.4 nmol mol(-1) creatinine. No difference was observed between the 3-OHBaP levels found at the end of the penultimate workday shift and those at the beginning of the last workday shift. Within these plants, the 1-OHP/3-OHBaP ratios varied greatly according to the workers' activity and emission sources. Using linear regression between these two metabolites, the 1-OHP level corresponding to the guidance value for 3-OHBaP ranged from 0.7 to 2.4 µmol mol(-1) creatinine, depending on the industrial sector. This study emphasizes the interest of monitoring urinary 3-OHBaP at the end of the last workday shift when working week exposure is relatively steady, and the irrelevance of a single guideline value for 1-OHP when assessing occupational health risk. © The Author 2014. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

  19. Ultimate load capacity assessment of reinforced concrete shell structures

    International Nuclear Information System (INIS)

    Gupta, Amita; Singh, R.K.; Kushwaha, H.S.; Mahajan, S.C.; Kakodkar, A.

    1993-01-01

    The objective of this study is to develop capability for prediction of ultimate load capacity of reinforced concrete shell structures. The present finite element code ULCA (Ultimate Load Capacity Assessment) adopts a degenerate concept of formulating general isoparametric shell element with a layered approach in the thickness direction. Different failure modes such as crushing, tensile cracking and reinforcement yielding are recognised for various problems. The structure fails by crushing of concrete when the concrete strain/stress reaches the ultimate stress or strain of concrete. Material nonlinearities as a result of tension cracking, tension stiffening between reinforcement and concrete in cracked region and yielding of reinforcement are considered along with geometric nonlinearity. Thus with this code it is possible to predict the pressure at which the first cracking, first through thickness cracking, first yielding of reinforcement occurs. After validating the code with few bench mark problems for different failure modes a reinforced concrete nuclear containment is analysed for its ultimate capacity and the results are matched with the published results. Further the ultimate load capacity of outer containment wall of Narora Atomic Power Station is predicted. It is observed that containment fails in membrane region and has a sufficient margin against design pressure. (author). 9 refs., 56 figs., 3 tabs., 1 appendix with 4 tabs

  20. Secondary metabolites from Ganoderma.

    Science.gov (United States)

    Baby, Sabulal; Johnson, Anil John; Govindan, Balaji

    2015-06-01

    Ganoderma is a genus of medicinal mushrooms. This review deals with secondary metabolites isolated from Ganoderma and their biological significance. Phytochemical studies over the last 40years led to the isolation of 431 secondary metabolites from various Ganoderma species. The major secondary compounds isolated are (a) C30 lanostanes (ganoderic acids), (b) C30 lanostanes (aldehydes, alcohols, esters, glycosides, lactones, ketones), (c) C27 lanostanes (lucidenic acids), (d) C27 lanostanes (alcohols, lactones, esters), (e) C24, C25 lanostanes (f) C30 pentacyclic triterpenes, (g) meroterpenoids, (h) farnesyl hydroquinones (meroterpenoids), (i) C15 sesquiterpenoids, (j) steroids, (k) alkaloids, (l) prenyl hydroquinone (m) benzofurans, (n) benzopyran-4-one derivatives and (o) benzenoid derivatives. Ganoderma lucidum is the species extensively studied for its secondary metabolites and biological activities. Ganoderma applanatum, Ganoderma colossum, Ganoderma sinense, Ganoderma cochlear, Ganoderma tsugae, Ganoderma amboinense, Ganoderma orbiforme, Ganoderma resinaceum, Ganoderma hainanense, Ganoderma concinna, Ganoderma pfeifferi, Ganoderma neo-japonicum, Ganoderma tropicum, Ganoderma australe, Ganoderma carnosum, Ganoderma fornicatum, Ganoderma lipsiense (synonym G. applanatum), Ganoderma mastoporum, Ganoderma theaecolum, Ganoderma boninense, Ganoderma capense and Ganoderma annulare are the other Ganoderma species subjected to phytochemical studies. Further phytochemical studies on Ganoderma could lead to the discovery of hitherto unknown biologically active secondary metabolites. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Two azole fungicides (carcinogenic triadimefon and non-carcinogenic myclobutanil) exhibit different hepatic cytochrome P450 activities in medaka fish

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chun-Hung [Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan (China); Chou, Pei-Hsin [Department of Environmental Engineering, National Cheng-Kung University, Tainan, Taiwan (China); Chen, Pei-Jen, E-mail: chenpj@ntu.edu.tw [Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan (China)

    2014-07-30

    Highlights: • We assess ecotoxicological impact of azole fungicides in the aquatic environment. • Carcinogenic and non-carcinogenic azoles show different CYP activities in medaka. • We compare azole-induced CYP expression and carcinogenesis between fish and rodents. • Liver CYP-enzyme induction is a key event in conazole-induced tumorigenesis. • We suggest toxicity evaluation methods for azole fungicides using medaka fish. - Abstract: Conazoles are a class of imidazole- or triazole-containing drugs commonly used as fungicides in agriculture and medicine. The broad application of azole drugs has led to the contamination of surface aquifers receiving the effluent of municipal or hospital wastewater or agricultural runoff. Several triazoles are rodent carcinogens; azole pollution is a concern to environmental safety and human health. However, the carcinogenic mechanisms associated with cytochrome P450 enzymes (CYPs) of conazoles remain unclear. We exposed adult medaka fish (Oryzias latipes) to continuous aqueous solutions of carcinogenic triadimefon and non-carcinogenic myclobutanil for 7 to 20 days at sub-lethal or environmentally relevant concentrations and assessed hepatic CYP activity and gene expression associated with CYP-mediated toxicity. Both triadimefon and myclobutanil induced hepatic CYP3A activity, but only triadimefon enhanced CYP1A activity. The gene expression of cyp3a38, cyp3a40, pregnane x receptor (pxr), cyp26b, retinoid acid receptor γ1 (rarγ1) and p53 was higher with triadimefon than myclobutanil. As well, yeast-based reporter gene assay revealed that 4 tested conazoles were weak agonists of aryl hydrocarbon receptor (AhR). We reveal differential CYP gene expression with carcinogenic and non-carcinogenic conazoles in a lower vertebrate, medaka fish. Liver CYP-enzyme induction may be a key event in conazole-induced tumorigenesis. This information is essential to evaluate the potential threat of conazoles to human health and fish

  2. Two azole fungicides (carcinogenic triadimefon and non-carcinogenic myclobutanil) exhibit different hepatic cytochrome P450 activities in medaka fish

    International Nuclear Information System (INIS)

    Lin, Chun-Hung; Chou, Pei-Hsin; Chen, Pei-Jen

    2014-01-01

    Highlights: • We assess ecotoxicological impact of azole fungicides in the aquatic environment. • Carcinogenic and non-carcinogenic azoles show different CYP activities in medaka. • We compare azole-induced CYP expression and carcinogenesis between fish and rodents. • Liver CYP-enzyme induction is a key event in conazole-induced tumorigenesis. • We suggest toxicity evaluation methods for azole fungicides using medaka fish. - Abstract: Conazoles are a class of imidazole- or triazole-containing drugs commonly used as fungicides in agriculture and medicine. The broad application of azole drugs has led to the contamination of surface aquifers receiving the effluent of municipal or hospital wastewater or agricultural runoff. Several triazoles are rodent carcinogens; azole pollution is a concern to environmental safety and human health. However, the carcinogenic mechanisms associated with cytochrome P450 enzymes (CYPs) of conazoles remain unclear. We exposed adult medaka fish (Oryzias latipes) to continuous aqueous solutions of carcinogenic triadimefon and non-carcinogenic myclobutanil for 7 to 20 days at sub-lethal or environmentally relevant concentrations and assessed hepatic CYP activity and gene expression associated with CYP-mediated toxicity. Both triadimefon and myclobutanil induced hepatic CYP3A activity, but only triadimefon enhanced CYP1A activity. The gene expression of cyp3a38, cyp3a40, pregnane x receptor (pxr), cyp26b, retinoid acid receptor γ1 (rarγ1) and p53 was higher with triadimefon than myclobutanil. As well, yeast-based reporter gene assay revealed that 4 tested conazoles were weak agonists of aryl hydrocarbon receptor (AhR). We reveal differential CYP gene expression with carcinogenic and non-carcinogenic conazoles in a lower vertebrate, medaka fish. Liver CYP-enzyme induction may be a key event in conazole-induced tumorigenesis. This information is essential to evaluate the potential threat of conazoles to human health and fish

  3. Ductility and Ultimate Capacity of Prestressed Steel Reinforced Concrete Beams

    Directory of Open Access Journals (Sweden)

    Chengquan Wang

    2017-01-01

    Full Text Available Nonlinear numerical analysis of the structural behaviour of prestressed steel reinforced concrete (PSRC beams was carried out by using finite element analysis software ABAQUS. By comparing the load-deformation curves, the rationality and reliability of the finite element model have been confirmed; moreover, the changes of the beam stiffness and stress in the forcing process and the ultimate bearing capacity of the beam were analyzed. Based on the model, the effect of prestressed force, and H-steel to the stiffness, the ultimate bearing capacity and ductility of beam were also analyzed.

  4. Ultimate load model test for Sizewell 'B' primary containment

    International Nuclear Information System (INIS)

    Crowder, R.

    1988-01-01

    This paper considers the factors influencing the adoption of an ultimate load factor for the Sizewell 'B' PWR primary containment structure. As part of the validation process for the ultimate load analysis method, a proposal has been made by Nuclear Design Associates to build and test a 1/10th scale model of the containment structure, which would proceed following the granting of section 2 consent for Sizewell 'B'. The modelling principles, construction method and test proposals are examined in some detail. The proposal is currently being considered by the CEGB's Project Management Team. (author)

  5. Ultimate pressure capacity of CANDU 6 containment structures

    International Nuclear Information System (INIS)

    Radulescu, J.P.; Pradolin, L.; Mamet, J.C.

    1997-01-01

    This paper summarizes the analytical work carried out and the results obtained when determining the ultimate pressure capacity (UPC) of the containment structures of CANDU 6 nuclear power plants. The purpose of the analysis work was to demonstrate that such containment structures are capable of meeting design requirements under the most severe accident conditions. For this concrete vessel subjected to internal pressure, the UPC was defined as the pressure causing through cracking in the concrete. The present paper deals with the overall behaviour of the containment. The presence of openings, penetrations and the ultimate pressure of the airlocks were considered separately. (author)

  6. ''Project Crystal'' for ultimate storage of highly radioactive waste

    International Nuclear Information System (INIS)

    Anon.

    1983-01-01

    NAGRA (The National Association for storage of radioactive waste) in Baden has launched in North Switzerland an extensive geological research program. The current research program, under the title of ''Project Crystal'', aims at providing the scientific knowledge which is required for the assessment of the suitability of the crystalline sub-soil of North Switzerland for the ultimate storage of highly radioactive waste. Safety and feasibility of such ultimate storage are in the forefront of preoccupations. Scientific institutes of France, Germany, USA and Canada are cooperating more particularly on boring research and laboratory analyses. Technical data are given on the USA and German installations used. (P.F.K.)

  7. Trump er gældsøkonomiens ultimative illusionist

    DEFF Research Database (Denmark)

    Nielsen, Peter

    2018-01-01

    Trump giver ikke kun gevaldige skattelettelser og nærer en illusion om, at vækst vil løse alle problemer. Han fortrænger også gældsøkonomiens ultimative bundlinje i form af klimaforandringerne.......Trump giver ikke kun gevaldige skattelettelser og nærer en illusion om, at vækst vil løse alle problemer. Han fortrænger også gældsøkonomiens ultimative bundlinje i form af klimaforandringerne....

  8. Methemoglobin Formation and Characterization of Hemoglobin Adducts of Carcinogenic Aromatic Amines and Heterocyclic Aromatic Amines.

    Science.gov (United States)

    Pathak, Khyatiben V; Chiu, Ting-Lan; Amin, Elizabeth Ambrose; Turesky, Robert J

    2016-03-21

    Arylamines (AAs) and heterocyclic aromatic amines (HAAs) are structurally related carcinogens formed during the combustion of tobacco or cooking of meat. They undergo cytochrome P450 mediated N-hydroxylation to form metabolites which bind to DNA and lead to mutations. The N-hydroxylated metabolites of many AAs also can undergo a co-oxidation reaction with oxy-hemolgobin (HbO2) to form methemoglobin (met-Hb) and the arylnitroso intermediates, which react with the β-Cys(93) chain of Hb to form Hb-arylsulfinamide adducts. The biochemistry of arylamine metabolism has been exploited to biomonitor certain AAs through their Hb arylsulfinamide adducts in humans. We examined the reactivity of HbO2 with the N-hydroxylated metabolites of 4-aminobiphenyl (ABP, HONH-ABP), aniline (ANL, HONH-ANL), and the HAAs 2-amino-9H-pyrido[2,3-b]indole (AαC, HONH-AαC), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP, HONH-PhIP), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx, HONH-MeIQx). HONH-ABP, HO-ANL, and HONH-AαC induced methemoglobinemia and formed Hb sulfinamide adducts. However, HONH-MeIQx and HONH-PhIP did not react with the oxy-heme complex, and met-Hb formation and chemical modification of the β-Cys(93) residue were negligible. Molecular modeling studies showed that the distances between the H-ON-AA or H-ON-HAA substrates and the oxy-heme complex of HbO2 were too far away to induce methemoglobinemia. Different conformational changes in flexible helical and loop regions around the heme pocket induced by the H-ON-AA or H-ON-HAAs may explain the different proclivities of these chemicals to induce methemoglobinemia. Hb-Cys(93β) sulfinamide and sulfonamide adducts of ABP, ANL, and AαC were identified, by Orbitrap MS, following the proteolysis of Hb with trypsin, Glu-C, or Lys-C. Hb sulfinamide and sulfonamide adducts of ABP were identified in the blood of mice exposed to ABP, by Orbitrap MS. This is the first report of the identification of intact Hb

  9. Carcinogenicity of methyl-tertiary butyl ether in gasoline.

    Science.gov (United States)

    Mehlman, Myron A

    2002-12-01

    Methyl tertiary butyl ether (MTBE) was added to gasoline on a nationwide scale in 1992 without prior testing of adverse, toxic, or carcinogenic effects. Since that time, numerous reports have appeared describing adverse health effects of individuals exposed to MTBE, both from inhalation of fumes in the workplace and while pumping gasoline. Leakage of MTBE, a highly water-soluble compound, from underground storage tanks has led to contamination of the water supply in many areas of the United States. Legislation has been passed by many states to prohibit the addition of MTBE to gasoline. The addition of MTBE to gasoline has not accomplished its stated goal of decreasing air pollution, and it has posed serious health risks to a large portion of the population, particularly the elderly and those with respiratory problems, asthma, and skin sensitivity. Reports of animal studies of carcinogenicity of MTBE began to appear in the 1990s, prior to the widespread introduction of MTBE into gasoline. These reports were largely ignored. In ensuing years, further studies have shown that MTBE causes various types of malignant tumors in mice and rats. The National Toxicology Program (NTP) Board of Scientific Counselors' Report on Carcinogens Subcommittee met in December 1998 to consider listing MTBE as "reasonably anticipated to be a human carcinogen." In spite of recommendations from Dr. Bailer, the primary reviewer, and other scientists on the committee, the motion to list MTBE in the report was defeated by a six to five vote, with one abstention. On the basis of animal studies, it is widely accepted that if a chemical is carcinogenic in appropriate laboratory animal test systems, it must be treated as though it were carcinogenic in humans. In the face of compelling evidence, NTP Committee members who voted not to list MTBE as "reasonably anticipated to be a human carcinogen" did a disservice to the general public; this action may cause needless exposure of many to health risks

  10. Metabolite Damage and Metabolite Damage Control in Plants

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, Andrew D. [Horticultural Sciences Department and; Henry, Christopher S. [Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, Illinois 60439, email:; Computation Institute, University of Chicago, Chicago, Illinois 60637; Fiehn, Oliver [Genome Center, University of California, Davis, California 95616, email:; de Crécy-Lagard, Valérie [Microbiology and Cell Science Department, University of Florida, Gainesville, Florida 32611, email: ,

    2016-04-29

    It is increasingly clear that (a) many metabolites undergo spontaneous or enzyme-catalyzed side reactions in vivo, (b) the damaged metabolites formed by these reactions can be harmful, and (c) organisms have biochemical systems that limit the buildup of damaged metabolites. These damage-control systems either return a damaged molecule to its pristine state (metabolite repair) or convert harmful molecules to harmless ones (damage preemption). Because all organisms share a core set of metabolites that suffer the same chemical and enzymatic damage reactions, certain damage-control systems are widely conserved across the kingdoms of life. Relatively few damage reactions and damage-control systems are well known. Uncovering new damage reactions and identifying the corresponding damaged metabolites, damage-control genes, and enzymes demands a coordinated mix of chemistry, metabolomics, cheminformatics, biochemistry, and comparative genomics. This review illustrates the above points using examples from plants, which are at least as prone to metabolite damage as other organisms.

  11. Ultimate deformation capacity of reinforced concrete slabs underblast load

    NARCIS (Netherlands)

    Doormaal, J.C.A.M. van; Weerheijm, J.

    1996-01-01

    In this paper a test method to determine the deformation capacity and the resistance-deformation curve of blast-loaded slabs is described. This method was developed at TNO-PML. The method has been used to determine the ultimate deformation capacity of some simply supported reinforced concrete slabs

  12. 49 Stories That Make an Ultimate STEM Lesson Plan

    Science.gov (United States)

    Mehta, Swati; Mehta, Rohit; Berzina-Pitcher, Inese; Seals, Christopher; Mishra, Punya

    2016-01-01

    In this paper we reviewed what 49 large urban public school district STEM teachers enrolled in a year-long graduate certificate and fellowship program at a large Midwestern university considered as their amazing teaching moments. They were asked to share their amazing teaching moments that would make an Ultimate Lesson Plan in STEM. In smaller…

  13. Ultimate capabilities of soft x-ray optics

    International Nuclear Information System (INIS)

    Vinogradov, A.V.; Zorev, N.N.; Kozhevnikov, I.V.

    1988-01-01

    Nonimaging soft X-ray optics is examined. The ultimate capabilities of a number of X-ray optical components designed for concentration and collimation of radiation from point sources are determined. The applications of X-ray optics are discussed together with the properties of materials in the X-ray range

  14. Safety related aspects of ultimate disposal of radioactive wastes

    International Nuclear Information System (INIS)

    Goemmel, R.

    1992-01-01

    Solutions and questions related to nuclear waste management are presented. In particular, long-term safety of repositories in Germany and Sweden is considered, with special attention being paid to methods of detection, geotechnical barriers and post-operational phase of salt dome repositories, and conditioning of wastes to make them fit for ultimate disposal. (DG) [de

  15. Analysis of ultimate-heat-sink spray ponds. Technical report

    International Nuclear Information System (INIS)

    Codell, R.

    1981-08-01

    This report develops models which can be utilized in the design of certain types of spray ponds used in ultimate heat sinks at nuclear power plants, and ways in which the models may be employed to determine the design basis required by U.S. Nuclear Regulatory Commission Regulatory Guide 1.27

  16. Trichloroethylene Biotransformation and its Role in Mutagenicity, Carcinogenicity and Target Organ Toxicity

    Science.gov (United States)

    Lash, Lawrence H.; Chiu, Weihsueh A.; Guyton, Kathryn Z.; Rusyn, Ivan

    2014-01-01

    Metabolism is critical for the mutagenicity, carcinogenicity, and other adverse health effects of trichloroethylene (TCE). Despite the relatively small size and simple chemical structure of TCE, its metabolism is quite complex, yielding multiple intermediates and end-products. Experimental animal and human data indicate that TCE metabolism occurs through two major pathways: cytochrome P450 (CYP)-dependent oxidation and glutathione (GSH) conjugation catalyzed by GSH S-transferases (GSTs). Herein we review recent data characterizing TCE processing and flux through these pathways. We describe the catalytic enzymes, their regulation and tissue localization, as well as the evidence for transport and inter-organ processing of metabolites. We address the chemical reactivity of TCE metabolites, highlighting data on mutagenicity of these end-products. Identification in urine of key metabolites, particularly trichloroacetate (TCA), dichloroacetate (DCA), trichloroethanol and its glucuronide (TCOH and TCOG), and N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NAcDCVC), in exposed humans and other species (mostly rats and mice) demonstrates function of the two metabolic pathways in vivo. The CYP pathway primarily yields chemically stable end-products. However, the GST pathway conjugate S-(1,2-dichlorovinyl)glutathione (DCVG) is further processed to multiple highly reactive species that are known to be mutagenic, especially in kidney where in situ metabolism occurs. TCE metabolism is highly variable across sexes, species, tissues and individuals. Genetic polymorphisms in several of the key enzymes metabolizing TCE and its intermediates contribute to variability in metabolic profiles and rates. In all, the evidence characterizing the complex metabolism of TCE can inform predictions of adverse responses including mutagenesis, carcinogenesis, and acute and chronic organ-specific toxicity. PMID:25484616

  17. Ultimate internal pressure capacity of concrete containment structures

    International Nuclear Information System (INIS)

    Krishnaswamy, C.N.; Namperumal, R.; Al-Dabbagh, A.

    1983-01-01

    Lesson learned from the accident at Three-Mile Island nuclear plant has necessitated the computation of the ultimate internal pressure capacity of containment structures as a licensing requirement in the U.S. In general, a containment structure is designed to be essentially elastic under design accident pressure. However, as the containment pressure builds up beyond the design value due to a more severe postulated accident, the containment response turns nonlinear as it sequentially passes through cracking of concrete, yielding of linear plate, yielding of rebar, and yielding of post-tensioning tendon (if the containment concrete is prestressed). This paper reports on the determination of the ultimate internal pressure capacity and nonlinear behavior of typical reinforced and prestressed concrete BWR containments. The probable modes of failure, the criteria for ultimate pressure capacity, and the most critical sections are described. Simple equations to hand-calculate the ultimate pressure capacity and the nonlinear behavior at membrane sections of the containment shell are presented. A nonlinear finite element analysis performed to determine the nonlinear behavior of the entire shell including nonmembrane sections is briefly discribed. The analysis model consisted of laminated axisymmetric shell finite elements with nonlinear stress-strain properties for each material. Results presented for typical BWR concrete containments include nonlinear response plots of internal pressure versus containment deflection and strains in the liner, rebar, and post-tensioning tendons at the most stressed section in the shell. Leak-tightness of the containment liner and the effect of thermal loads on the ultimate capacity are discussed. (orig.)

  18. Indoor air - assessment: Methods of analysis for environmental carcinogens

    International Nuclear Information System (INIS)

    Peterson, M.R.; Naugle, D.F.; Berry, M.A.

    1990-06-01

    The monograph describes, in a general way, published sampling procedures and analytical approaches for known and suspected carcinogens. The primary focus is upon carcinogens found in indoor air, although the methods described are applicable to other media or environments. In cases where there are no published methods for a particular pollutant in indoor air, methods developed for the workplace and for ambient air are included since they should be adaptable to indoor air. Known and suspected carcinogens have been grouped into six categories for the purposes of this and related work. The categories are radon, asbestos, organic compounds, inorganic species, particles, and non-ionizing radiation. Some methods of assessing exposure that are not specific to any particular pollutant category are covered in a separate section. The report is the fifth in a series of EPA/Environmental Criteria and Assessment Office Monographs

  19. Cable tray ultimate strength test employing a large shaker table

    Energy Technology Data Exchange (ETDEWEB)

    Komatsu, K.; Myojin, K.; Imai, K. [The Kansai Electric Power Co., Osaka (Japan); Fuyama, H. [Mitsubishi Heavy Industries Ltd, Takasago (Japan); Kokubo, E. [Mitsubishi Heavy Industdries Ltd, Kobe (Japan)

    2004-07-01

    Ultimate behaviors of cable trays, used in nuclear plants, have not been well studied since cable trays are designed based on conservative design criteria. In this study, by employing a large shaker table, an ultimate strength test was conducted for cable trays used in nuclear power plants. This report describes the results of shaker table test. The following results were obtained. First, in an S{sub 2} earthquake, the damping ratio was so large - more than 30% due to the rubbing of cables - that a large response was not present and the strains in the support were within the elastic limits. Secondly, the support was strong enough to sustain the cable trays even when the strain in the support was 20 times larger than the elastic limit. (authors)

  20. Landau damping: the mechanics model and its ultimate entropy gain

    International Nuclear Information System (INIS)

    Hannay, J H; Kluge, Michel

    2011-01-01

    Classical mechanics has only been invoked to account for Landau damping in a rather half-hearted way, alongside plasma perturbation theory. In particular this invocation is essential for the study of the saturation, or post-linear (or 'nonlinear') regime of the damping initiated by Dawson and O'Neill. By embracing mechanics wholeheartedly here, with its attendant phase space, one can access results, old and new, cleanly and directly, and with one fewer numerical integration for the post-linear regime. By using a summation technique familiar in semiclassical quantum mechanics (Poisson summation), the one remaining numerical integration can be much improved in accuracy. Also accessible from mechanics is the ultimate entropy gain. Though zero for any finite time (in the absence of coarse graining), the entropy gain is ultimately non-zero (at infinite time the required coarse graining is zero). It is calculated analytically by using the appropriate asymptotics, hitherto not fully exploited.

  1. Management and ultimate storage of wastes from nuclear power generation

    International Nuclear Information System (INIS)

    1989-09-01

    The annotation on R and D prorgam 86 parts I-II have been brought together in the present report part I, together with some general viewpoints, and been classified according to subject. Part II of the present report comprises viewpoints of 'Research Program 1987-1992' and part III of 'Alternative methods of ultimate storage'. Swedish and French viewpoints are presented in Swedish, the remaining foreign material in English. The comments are grouped in subject catergories. (O.S.)

  2. The ultimate challenge of pregnancy-associated breast carcinoma

    International Nuclear Information System (INIS)

    Raja, R.; Tahira, A.

    2005-01-01

    Pregnancy associated breast carcinoma requires making judicious use of all diagnostic modalities and the therapeutic options of surgery, irradiation, chemotherapy and hormonal therapy to enhance survival rates. Individualization of treatment for each patient is the key to success. The effects on future fertility, the time interval before next conception, and whether to breast feed or not are all well-documented. A multidisciplinary coordinated team approach to this ultimate challenge of patient care will prove fruitful. (author)

  3. Ultimate Gradient Limitation in Niobium Superconducting Accelerating Cavities

    Energy Technology Data Exchange (ETDEWEB)

    Checchin, Mattia [Illinois Inst. of Technology, Chicago, IL (United States); Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Grassellino, Anna [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Martinello, Martina [Illinois Inst. of Technology, Chicago, IL (United States); Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Posen, Sam [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Romanenko, Alexander [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Zasadzinski, John [Illinois Inst. of Technology, Chicago, IL (United States)

    2016-06-01

    The present study is addressed to the theoretical description of the ultimate gradient limitation in SRF cavities. Our intent is to exploit experimental data to confirm models which provide feed-backs on how to improve the current state-of-art. New theoretical insight on the cavities limiting factor can be suitable to improve the quench field of N-doped cavities, and therefore to take advantage of high Q0 at high gradients.

  4. Ultimate capacity of piles penetrating in weak soil layers

    Directory of Open Access Journals (Sweden)

    Al-Obaidi Ahmed

    2018-01-01

    Full Text Available A pile foundation is one of the most popular forms of deep foundations. They are routinely employed to transfer axial structure loads through the soft soil to stronger bearing strata. Piles generally used to increase the load carrying capacity of the foundation and reduce the settlement of the foundation. On the other hand, many cases in practice where piles pass through different layers of soil that contain weak layers located at different depths and extension, also some time cavities with a different shape, size, and depth are found. In this study, a total of 96 cases is considered and simulated in PLAXIS 2D program aiming to understand the influence of weak soil on the ultimate pile capacity. The piles embedded in the dense sand with a layer of weak soil at different extension and location. The cross section of the geometry used in this study was designed as an axisymmetric model with the 15-node element; the boundary condition recommended at least 5D in the horizontal direction, and (L+5D in the vertical direction where D and L are the diameter and length of pile, respectively. The soil is modeled as Mohr-Coulomb, with five input parameters and the behavior of pile material represented by the linear elastic model. The results of the above cases are compared with the results found in a pile embedded in dense soil without weak layers or cavities. The results indicated that the existence of weak soil layer within the surrounding soil around the pile decreases the ultimate capacity. Furthermore, it has been found that increase in the weak soil width (extension leads to reduction in the ultimate capacity of the pile. This phenomenon is applicable to all depth of weak soil. The influence of weak layer extension on the ultimate capacity is less when it is presentin the upper soil layers.

  5. Ultimate survival in anomalous ψ(2S) decays

    International Nuclear Information System (INIS)

    Gérard, Jean-Marc; Martini, Antony

    2014-01-01

    The hierarchy among the radiative γ(π 0 ,η,η ′ ) decay channels for the ψ ′ looks quite different from the J/ψ one. The fate of charm, namely an ultimate survival of on-shell cc ¯ intermediate states, might give us the clue for this new puzzle in exclusive charmonium decays. A similar self-preservation has already been invoked in the past to solve the so-called ρπ puzzle.

  6. Hydrogeological problems in the ultimate storage of radioactive wastes

    International Nuclear Information System (INIS)

    Uerpmann, E.P.

    1980-01-01

    The following work shows how one can achieve the safe closure of ultimate-stored radioactive wastes by connecting a series of various barriers to the biosphere. The propagation of radionuclides by ground water is considered to be the most important long-term transport mechanism. Salt occurences in the Federal Republic of Germany are considered to be the best form suitable for end storage formations for known reasons. When not observing mining and hydrogeological knowledge, the danger of uncontrollable water flow in the end storage can arise from the water solubility of the salt rocks. Therefore the filling of salt mines and the subsequent procedures are dealt with in detail. The leading of radioactive nuclides is influenced by the properties of the ultimately stored wastes and by the quality of the remaining filling of the caves. These problems are dealt with in detail. A series of barriers to the closure of the underground caves are suggested and discussed. The most important barriers consist of the stability of the corresponding selected end storage structure. Possible arrangements of the storage cave are given which even after storage must maintain a high stability. Proposals are made on how the ultimately stored wastes can protect themselves against contact with free water or salt solutions. (orig.) [de

  7. Ultimate concerns in late modernity: Archer, Bourdieu and reflexivity.

    Science.gov (United States)

    Farrugia, David; Woodman, Dan

    2015-12-01

    Through a critique of Margaret Archer's theory of reflexivity, this paper explores the theoretical contribution of a Bourdieusian sociology of the subject for understanding social change. Archer's theory of reflexivity holds that conscious 'internal conversations' are the motor of society, central both to human subjectivity and to the 'reflexive imperative' of late modernity. This is established through critiques of Bourdieu, who is held to erase creativity and meaningful personal investments from subjectivity, and late modernity is depicted as a time when a 'situational logic of opportunity' renders embodied dispositions and the reproduction of symbolic advantages obsolete. Maintaining Archer's focus on 'ultimate concerns' in a context of social change, this paper argues that her theory of reflexivity is established through a narrow misreading and rejection of Bourdieu's work, which ultimately creates problems for her own approach. Archer's rejection of any pre-reflexive dimensions to subjectivity and social action leaves her unable to sociologically explain the genesis of 'ultimate concerns', and creates an empirically dubious narrative of the consequences of social change. Through a focus on Archer's concept of 'fractured reflexivity', the paper explores the theoretical necessity of habitus and illusio for understanding the social changes that Archer is grappling with. In late modernity, reflexivity is valorized just as the conditions for its successful operation are increasingly foreclosed, creating 'fractured reflexivity' emblematic of the complex contemporary interaction between habitus, illusio, and accelerating social change. © London School of Economics and Political Science 2015.

  8. Carcinogenic effect of petroleum and its by-products

    Energy Technology Data Exchange (ETDEWEB)

    Gimadeev, M M

    1962-01-01

    A review of literature on the carcinogenic effect of petroleum and its by-products are briefly discussed. Many of the products can induce hyperkeratosis, folliculitis, verruca, pulmonary adenoma, skin cancer, etc. Their action is mainly local but they can also be multicentric. Although a number of groups have made chemical analyses of various petroleums and peroleum products, results were generally negative with respect to 3,4-benzypyrene, although 40 to 68 microg/g was found in 1 crude petroleum. At present it appears that much of the carcinogenic action of these materials resides in polycyclic hydrocarbons about which little is known.

  9. Environmental carcinogens in human target tissues in culture: Progress report

    International Nuclear Information System (INIS)

    Hsu, I.C.

    1987-01-01

    We have accumulated more experimental evidences that demonstrated the comparative approaches with human cells will allow us to predict human risk with good accuracy following exposure to toxic chemicals. We also synthesized several carcinogenic DNA adducts, i.e., the major benzo[a]pyrene DNA adduct, 0 6 -methyldeoxyguanosine, 7-methyl- deoxyguanosine and 2-methyl-deoxyguanosine to be used as standards for quantitating DNA adduct formation in carcinogen exposed cells. A simple synthetic method was developed for preparation of the major B[a]p DNA adduct with yields better than those reported. The main accomplishments related to the originally stated objectives are summarized. 8 refs., 2 figs., 1 tab

  10. Cannabis and tobacco smoke are not equally carcinogenic

    Directory of Open Access Journals (Sweden)

    Melamede Robert

    2005-10-01

    Full Text Available Abstract More people are using the cannabis plant as modern basic and clinical science reaffirms and extends its medicinal uses. Concomitantly, concern and opposition to smoked medicine has occurred, in part due to the known carcinogenic consequences of smoking tobacco. Are these reactions justified? While chemically very similar, there are fundamental differences in the pharmacological properties between cannabis and tobacco smoke. Cannabis smoke contains cannabinoids whereas tobacco smoke contains nicotine. Available scientific data, that examines the carcinogenic properties of inhaling smoke and its biological consequences, suggests reasons why tobacco smoke, but not cannabis smoke, may result in lung cancer.

  11. Mutagenic and carcinogenic structural alerts and their mechanisms of action.

    Science.gov (United States)

    Plošnik, Alja; Vračko, Marjan; Dolenc, Marija Sollner

    2016-09-01

    Knowing the mutagenic and carcinogenic properties of chemicals is very important for their hazard (and risk) assessment. One of the crucial events that trigger genotoxic and sometimes carcinogenic effects is the forming of adducts between chemical compounds and nucleic acids and histones. This review takes a look at the mechanisms related to specific functional groups (structural alerts or toxicophores) that may trigger genotoxic or epigenetic effects in the cells. We present up-to-date information about defined structural alerts with their mechanisms and the software based on this knowledge (QSAR models and classification schemes).

  12. Modification of carcinogenic and antitumor radiation effects (biomedical aspects)

    International Nuclear Information System (INIS)

    Vilenchik, M.M.

    1985-01-01

    In the book the data on modification of carcinogenic radiation effects by physiologicaly active compounds (caffeine, hormones, promoters and others) as well as on potentiation of antitumor radiation effects by means of hyperthermia are systematized. It is shown that as a basis of synergetic (superadditive) carcinogenic or antitumor radiation effects combined with other factor can be the inhibiting effects of the latter on the reparation process of radiation-induced DNA injuries. The results of experimental investigations and the data on quantitative analysis can be used as a theoretical basis for improvement of the ways and means of the prophylaxis of tumor diseases as well as for increasing the efficiency of radiotherapy

  13. A call to expand regulation to all carcinogenic fibrous minerals

    Science.gov (United States)

    Baumann, F.; Steele, I.; Ambrosi, J.; Carbone, M.

    2013-05-01

    The regulatory term "asbestos" groups only the six fibrous minerals that were commercially used among approximately 400. The carcinogenicity of these six regulated minerals has been largely demonstrated and is related to fiber structure, fiber length/diameter ratio, and bio-persistence. From a public perception, the generic term "asbestos" refers to the fibrous minerals that cause asbestosis, mesothelioma and other cancers. However, other non-regulated fibrous minerals are potentially as dangerous as the regulatory asbestos because they share similar physical and chemical properties, epidemiological studies have demonstrated their relationship with asbestos-related diseases, and both in vitro and in vivo experiments have established the toxicity of these minerals. For example, the non-regulated asbestiform winchite and richterite minerals that contaminated the vermiculite mined from Libby, Montana, (USA) were associated with mesothelioma, lung cancer and asbestosis observed among the area's residents and miners. Many other examples of non-regulated carcinogenic fibrous minerals include, but are not limited to, antigorite, arfvedsonite, balangeroite, carlosturanite, erionite, fluoro-edenite, hornblende, mordenite, palygorskite, and sepiolite. To propose a regulatory definition that would provide protection from all carcinogenic fibers, we have conducted an interdisciplinary literature review to compare the characteristics of "asbestos" and of non-regulated mineral fibers that relate to carcinogenicity. We specifically studied two non-regulated fibrous minerals that are associated with asbestos-related diseases: the serpentine antigorite and the zeolite erionite. Both examples underscore the problem of regulation based on commercial, rather than scientific principles: 1) the occurrence of fibrous antigorite in materials used to pave roads has been correlated with high mesothelioma rates in New Caledonia. Antigorite was also the cause of asbestosis in Poland, and in

  14. Production of Metabolites

    DEFF Research Database (Denmark)

    2011-01-01

    A recombinant micro-organism such as Saccharomyces cerevisiae which produces and excretes into culture medium a stilbenoid metabolite product when grown under stilbenoid production conditions, which expresses in above native levels a ABC transporter which transports said stilbenoid out of said...... micro-organism cells to the culture medium. The genome of the Saccharomyces cerevisiae produces an auxotrophic phenotype which is compensated by a plasmid which also expresses one or more of said enzymes constituting said metabolic pathway producing said stilbenoid, an expression product of the plasmid...

  15. Mutagenic azide metabolite is azidoalanine

    International Nuclear Information System (INIS)

    Owais, W.M.; Rosichan, J.L.; Ronald, R.C.; Kleinhofs, A.; Nilan, R.A.

    1981-01-01

    Sodium axide produces high mutation rates in a number of species. Azide mutagenicity is mediated through a metabolite in barley and bacteria. Many studies showed that azide affects the L-cysteine biosynthesis pathway. Cell-free extracts of Salmonella typhimurium convert azide and O-acetylserine to the mutagenic metabolite. O-acetylserine sulfhydrylase was identified as the enzyme responsible for the metabolite biosynthesis. To confirm the conclusion that the azide metabolite is formed through the β-substitution pathway of L-cysteine, we radioactively labeled the azide metabolite using 14 C-labeled precursors. Moreover, the mutagenic azide metabolite was purified and identified as azidoalanine based on mass spectroscopy and elemental analysis. 26 refs., 3 figs., 1 tab

  16. DNA repair studies in mouse germ cells exposed to two carcinogens and two non-carcinogens

    International Nuclear Information System (INIS)

    Sega, G.A.; Owens, J.G.

    1987-01-01

    An in vivo test was used to measure induced unscheduled DNA synthesis (UDS) in the germ cells of male mice exposed to the carcinogens benzo(a)pyrene [B(a)P] and 2-acetylaminofluorene (2AAF), and to the noncarcinogens pyrene (PYR) and 4-acetylaminofluorene (4AAF). Early spermatids, a DNA-repair competent stage, were used to test the effects of all chemicals. After chemical treatment and testicular injection of [ 3 H]dThd, sperm were recovered 16 days later from the caudal epididymides (these sperm were in early spermatid stages at the time of treatment) and assayed for the unscheduled incorporation of [ 3 H]dThd using liquid scintillation counting (LSC). Exposures of 2AAF ranged from 125 to 1600 mg/kg, 4AAF from 125 to 2000 mg/kg, PYR from 100 to 600 mg/kg, B(a)P from 100 to 400 mg/kg. Chemicals were administered both by intraperitoneal (i.p.) injection and by gavage. Methyl methanesulfonate (MMS) was used as a positive control

  17. Towards a new method for the quantification of metabolites in the biological sample

    International Nuclear Information System (INIS)

    Neugnot, B.

    2005-03-01

    The quantification of metabolites is a key step in drug development. The aim of this Ph.D. work was to study the feasibility of a new method for this quantification, in the biological sample, without the drawbacks (cost, time, ethics) of the classical quantification methods based on metabolites synthesis or administration to man of the radiolabelled drug. Our strategy consists in determining the response factor, in mass spectrometry, of the metabolites. This approach is based on tritium labelling of the metabolites, ex vivo, by isotopic exchange. The labelling step was studied with deuterium. Metabolites of a model drug, recovered from in vitro or urinary samples, were labelled by three ways (Crab tree's catalyst ID2, deuterated trifluoroacetic acid or rhodium chloride ID20). Then, the transposition to tritium labelling was studied and the first results are very promising for the ultimate validation of the method. (author)

  18. Development of novel metabolite-responsive transcription factors via transposon-mediated protein fusion.

    Science.gov (United States)

    Younger, Andrew K D; Su, Peter Y; Shepard, Andrea J; Udani, Shreya V; Cybulski, Thaddeus R; Tyo, Keith E J; Leonard, Joshua N

    2018-02-01

    Naturally evolved metabolite-responsive biosensors enable applications in metabolic engineering, ranging from screening large genetic libraries to dynamically regulating biosynthetic pathways. However, there are many metabolites for which a natural biosensor does not exist. To address this need, we developed a general method for converting metabolite-binding proteins into metabolite-responsive transcription factors-Biosensor Engineering by Random Domain Insertion (BERDI). This approach takes advantage of an in vitro transposon insertion reaction to generate all possible insertions of a DNA-binding domain into a metabolite-binding protein, followed by fluorescence activated cell sorting to isolate functional biosensors. To develop and evaluate the BERDI method, we generated a library of candidate biosensors in which a zinc finger DNA-binding domain was inserted into maltose binding protein, which served as a model well-studied metabolite-binding protein. Library diversity was characterized by several methods, a selection scheme was deployed, and ultimately several distinct and functional maltose-responsive transcriptional biosensors were identified. We hypothesize that the BERDI method comprises a generalizable strategy that may ultimately be applied to convert a wide range of metabolite-binding proteins into novel biosensors for applications in metabolic engineering and synthetic biology. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard

    NARCIS (Netherlands)

    Rusyn, Ivan; Chiu, Weihsueh A.; Lash, Lawrence H.; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z.

    2014-01-01

    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic

  20. Classification of carcinogenic and mutagenic properties using machine learning method

    DEFF Research Database (Denmark)

    Moorthy, N. S.Hari Narayana; Kumar, Surendra; Poongavanam, Vasanthanathan

    2017-01-01

    An accurate calculation of carcinogenicity of chemicals became a serious challenge for the health assessment authority around the globe because of not only increased cost for experiments but also various ethical issues exist using animal models. In this study, we provide machine learning...

  1. In vitro transformation: interactions of chemical carcinogens and radiation

    International Nuclear Information System (INIS)

    DiPaolo, J.A.

    1976-01-01

    The development of reproducible quantitative in vitro procedures resulting in neoplastic transformation of mammalian cells has made possible the separation of events related to the process leading to transformation from secondary events that interfere with the early recognition of transformation. The use of chemical carcinogens on Syrian hamster cell strains results in a dose-response relation consistent with a Poisson distribution, indicating that the transformation phenomenon is inductive. In some circumstances, the joint action or interaction of chemical carcinogens with other agents results in an increased incidence of transformation. The pretreatment of Syrian hamster cells with ionizing radiation (250 R) or alkylating chemicals enhances the frequency of transformation on a cell or colony basis ordinarily obtained with known chemical carcinogens. Pretreatment with non-ionizing irradiation (uv, 254 nm) did not have a similar effect. The two types of irradiation and the alkylating agents reduced the cloning efficiency of the cells. X ray alone produced no transformation; the alkylating chemicals produced transformations infrequently, whereas uv produced a significant number of transformations. The number of transformations associated with uv is increased by pretreatment of the cells by x-irradiation. The enhancement of transformation by x-ray or x-ray-type agents appears to be independent of the type of second carcinogen used

  2. Chemical procedures to detect carcinogenic compound in domestic wastewater

    International Nuclear Information System (INIS)

    Abd Manan T S; Malakahmad A

    2013-01-01

    This review presents chemical methods to detect carcinogenic compound in wastewater. Atomic absorption spectroscopy (AAS), high performance liquid chromatography (HPLC) and gas chromatography mass spectroscopy (GCMS) and their alternative attached equipments were discussed. The application of each method is elaborated using related studies in the field.

  3. Mycotoxins as human carcinogens-the IARC Monographs classification.

    Science.gov (United States)

    Ostry, Vladimir; Malir, Frantisek; Toman, Jakub; Grosse, Yann

    2017-02-01

    Humans are constantly exposed to mycotoxins (e.g. aflatoxins, ochratoxins), mainly via food intake of plant and animal origin. The health risks stemming from mycotoxins may result from their toxicity, in particular their carcinogenicity. In order to prevent these risks, the International Agency for Research on Cancer (IARC) in Lyon (France)-through its IARC Monographs programme-has performed the carcinogenic hazard assessment of some mycotoxins in humans, on the basis of epidemiological data, studies of cancer in experimental animals and mechanistic studies. The present article summarizes the carcinogenic hazard assessments of those mycotoxins, especially aflatoxins (aflatoxin B 1 , B 2 , G 1 , G 2 and M 1 ), fumonisins (fumonisin B 1 and B 2 ) and ochratoxin A (OTA). New information regarding the genotoxicity of OTA (formation of OTA-DNA adducts), the role of OTA in oxidative stress and the identification of epigenetic factors involved in OTA carcinogenesis-should they indeed provide strong evidence that OTA carcinogenicity is mediated by a mechanism that also operates in humans-could lead to the reclassification of OTA.

  4. Carcinogenicity assessment of water-soluble nickel compounds.

    Science.gov (United States)

    Goodman, Julie E; Prueitt, Robyn L; Dodge, David G; Thakali, Sagar

    2009-01-01

    IARC is reassessing the human carcinogenicity of nickel compounds in 2009. To address the inconsistencies among results from studies of water-soluble nickel compounds, we conducted a weight-of-evidence analysis of the relevant epidemiological, toxicological, and carcinogenic mode-of-action data. We found the epidemiological evidence to be limited, in that some, but not all, data suggest that exposure to soluble nickel compounds leads to increased cancer risk in the presence of certain forms of insoluble nickel. Although there is no evidence that soluble nickel acts as a complete carcinogen in animals, there is limited evidence that suggests it may act as a tumor promoter. The mode-of-action data suggest that soluble nickel compounds will not be able to cause genotoxic effects in vivo because they cannot deliver sufficient nickel ions to nuclear sites of target cells. Although the mode-of-action data suggest several possible non-genotoxic effects of the nickel ion, it is unclear whether soluble nickel compounds can elicit these effects in vivo or whether these effects, if elicited, would result in tumor promotion. The mode-of-action data equally support soluble nickel as a promoter or as not being a causal factor in carcinogenesis at all. The weight of evidence does not indicate that soluble nickel compounds are complete carcinogens, and there is only limited evidence that they could act as tumor promoters.

  5. CARCINOGENIC EFFECTS OF LOW DOSES OF IONIZING RADIATION

    Science.gov (United States)

    Carcinogenic Effects of Low Doses of Ionizing RadiationR Julian Preston, Environmental Carcinogenesis Division, NHEERL, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711The form of the dose-response curve for radiation-induced cancers, particu...

  6. Rapid population growth and environmental degradation: ultimate versus proximate factors.

    Science.gov (United States)

    Shaw, R P

    1989-01-01

    This philosophical review of 2 arguments about responsibility for and solutions to environmental degradation concludes that both sides are correct: the ultimate and the proximal causes. Ultimate causes of pollution are defined as the technology responsible for a given type of pollution, such as burning fossil fuel; proximate causes are defined as situation-specific factors confounding the problem, such as population density or rate of growth. Commoner and others argue that developed countries with low or negative population growth rates are responsible for 80% of world pollution, primarily in polluting technologies such as automobiles, power generation, plastics, pesticides, toxic wastes, garbage, warfaring, and nuclear weapons wastes. Distortionary policies also contribute; examples are agricultural trade protection, land mismanagement, urban bias in expenditures, and institutional rigidity., Poor nations are responsible for very little pollution because poverty allows little waste or expenditures for polluting, synthetic technologies. The proximal causes of pollution include numbers and rate of growth of populations responsible for the pollution. Since change in the ultimate cause of pollution remains out of reach, altering the numbers of polluters can make a difference. Predictions are made for proportions of the world's total waste production, assuming current 1.6 tons/capita for developed countries and 0.17 tons/capita for developing countries. If developing countries grow at current rates and become more wealthy, they will be emitting half the world's waste by 2025. ON the other hand, unsustainable population growth goes along with inadequate investment in human capital: education, health, employment, infrastructure. The solution is to improve farming technologies in the 117 non-self-sufficient countries, fund development in the most unsustainable enclaves of growing countries, break institutionalized socio-political rigidity in these enclaves, and focus on

  7. Risk-based indicators of Canadians' exposures to environmental carcinogens.

    Science.gov (United States)

    Setton, Eleanor; Hystad, Perry; Poplawski, Karla; Cheasley, Roslyn; Cervantes-Larios, Alejandro; Keller, C Peter; Demers, Paul A

    2013-02-12

    Tools for estimating population exposures to environmental carcinogens are required to support evidence-based policies to reduce chronic exposures and associated cancers. Our objective was to develop indicators of population exposure to selected environmental carcinogens that can be easily updated over time, and allow comparisons and prioritization between different carcinogens and exposure pathways. We employed a risk assessment-based approach to produce screening-level estimates of lifetime excess cancer risk for selected substances listed as known carcinogens by the International Agency for Research on Cancer. Estimates of lifetime average daily intake were calculated using population characteristics combined with concentrations (circa 2006) in outdoor air, indoor air, dust, drinking water, and food and beverages from existing monitoring databases or comprehensive literature reviews. Intake estimates were then multiplied by cancer potency factors from Health Canada, the United States Environmental Protection Agency, and the California Office of Environmental Health Hazard Assessment to estimate lifetime excess cancer risks associated with each substance and exposure pathway. Lifetime excess cancer risks in excess of 1 per million people are identified as potential priorities for further attention. Based on data representing average conditions circa 2006, a total of 18 carcinogen-exposure pathways had potential lifetime excess cancer risks greater than 1 per million, based on varying data quality. Carcinogens with moderate to high data quality and lifetime excess cancer risk greater than 1 per million included benzene, 1,3-butadiene and radon in outdoor air; benzene and radon in indoor air; and arsenic and hexavalent chromium in drinking water. Important data gaps were identified for asbestos, hexavalent chromium and diesel exhaust in outdoor and indoor air, while little data were available to assess risk for substances in dust, food and beverages. The ability to

  8. Adobe Photoshop CS5 for Photographers The Ultimate Workshop

    CERN Document Server

    Evening, Martin

    2010-01-01

    If you already have a good knowledge of Adobe Photoshop and are looking to advance your skills, Adobe Photoshop CS5 for Photographers: The Ultimate Workshop is the book you've been waiting for.  Renowned photographers Martin Evening and Jeff Schewe impart their Photoshop tips and workflow, showing you how to use a vast array of rarely seen advanced Photoshop techniques.  Whether the subject is serious retouching work, weird and wonderful compositions, or planning a shoot before you've even picked up a camera, you can be sure that the advice is based on years of practical experience.

  9. Ultimate survival in anomalous ψ(2S) decays

    Energy Technology Data Exchange (ETDEWEB)

    Gérard, Jean-Marc; Martini, Antony

    2014-03-07

    The hierarchy among the radiative γ(π{sup 0},η,η{sup ′}) decay channels for the ψ{sup ′} looks quite different from the J/ψ one. The fate of charm, namely an ultimate survival of on-shell cc{sup ¯} intermediate states, might give us the clue for this new puzzle in exclusive charmonium decays. A similar self-preservation has already been invoked in the past to solve the so-called ρπ puzzle.

  10. Determination of Ultimate Torque for Multiply Connected Cross Section Rod

    Directory of Open Access Journals (Sweden)

    V. L. Danilov

    2015-01-01

    Full Text Available The aim of this work is to determine load-carrying capability of the multiply cross-section rod. This calculation is based on the model of the ideal plasticity of the material, so that the desired ultimate torque is a torque at which the entire cross section goes into a plastic state.The article discusses the cylindrical multiply cross-section rod. To satisfy the equilibrium equation and the condition of plasticity simultaneously, two stress function Ф and φ are introduced. By mathematical transformations it has been proved that Ф is constant along the path, and a formula to find its values on the contours has been obtained. The paper also presents the rationale of the line of stress discontinuity and obtained relationships, which allow us to derive the equations break lines for simple interaction of neighboring circuits, such as two lines, straight lines and circles, circles and a different sign of the curvature.After substitution into the boundary condition at the end of the stress function Ф and mathematical transformations a formula is obtained to determine the ultimate torque for the multiply cross-section rod.Using the doubly connected cross-section and three-connected cross-section rods as an example the application of the formula of ultimate torque is studied.For doubly connected cross-section rod, the paper offers a formula of the torque versus the radius of the rod, the aperture radius and the distance between their centers. It also clearly demonstrates the torque dependence both on the ratio of the radii and on the displacement of hole. It is shown that the value of the torque is more influenced by the displacement of hole, rather than by the ratio of the radii.For the three-connected cross-section rod the paper shows the integration feature that consists in selection of a coordinate system. As an example, the ultimate torque is found by two methods: analytical one and 3D modeling. The method of 3D modeling is based on the Nadai

  11. Toxic and carcinogenic agents in dry and moist snuff.

    Science.gov (United States)

    Hoffmann, D; Adams, J D; Lisk, D; Fisenne, I; Brunnemann, K D

    1987-12-01

    The oral use of snuff is causatively associated with cancer of the oral cavity. Since most epidemiologic studies to date relate to the long-term use of dry snuff, which has dominated the U.S. smokeless tobacco market in the past, the concentrations of several toxic and carcinogenic agents in the three most popular dry snuff brands have been compared with those in the five most popular moist snuff brands sold in the United States. All eight samples were analyzed for nitrate, alkaloids, polyphenols, volatile carbonyl compounds, lead, cadmium, selenium, and the carcinogenic compounds benzo[a]pyrene (CAS: 50-32-8), polonium-210 (CAS: 13981-52-7), volatile N-nitrosamines (VNAs), N-nitrosodiethanolamine (CAS: 1116-54-7), and the tobacco-specific N-nitrosamines (TSNAs). Most of the snuff brands were rich in nitrate (greater than or equal to 1.5%), total polyphenols (greater than 2%), and in nicotine (greater than or equal to 1.5%), which is the habituating factor in tobacco use. Concentrations of the VNAs were significantly above the permissible limits set for some food products; the concentrations of the TSNAs in both snuff types exceeded the levels of nitrosamines in other consumer products by at least two to three orders of magnitude. The extremely high levels of the TSNAs in snuff have remained unchanged during the last decade and present the major carcinogenic risk factor for the oral use of snuff. Polonium-210 contributes further to the carcinogenic risk associated with snuff. The chemical-analytical data presented in this study do not indicate marked differences in the carcinogenic potential of moist snuff compared to dry snuff.

  12. USING PROTEOMICS TO MONITOR PROTEIN EXPRESSION IN HUMAN CELLS EXPOSED TO CARCINOGENS

    Science.gov (United States)

    People are continuously exposed exogenously to varying amounts of chemicals that have been shown to have carcinogenic properties in experimental systems. It has been estimated that exposure to environmental chemical carcinogens in the environment may contribute significantly to t...

  13. 75 FR 60133 - Agency Information Collection Activities: Declaration of Ultimate Consignee That Articles Were...

    Science.gov (United States)

    2010-09-29

    ... Activities: Declaration of Ultimate Consignee That Articles Were Exported for Temporary Scientific or... the Declaration of Ultimate Consignee That Articles Were Exported for Temporary Scientific or...: Title: Declaration of Ultimate Consignee That Articles Were Exported for Temporary Scientific or...

  14. The prospects of transition metal dichalcogenides for ultimately scaled CMOS

    Science.gov (United States)

    Thiele, S.; Kinberger, W.; Granzner, R.; Fiori, G.; Schwierz, F.

    2018-05-01

    MOSFET gate length scaling has been a main source of progress in digital electronics for decades. Today, researchers still spend considerable efforts on reducing the gate length and on developing ultimately scaled MOSFETs, thereby exploring both new device architectures and alternative channel materials beyond Silicon such as two-dimensional TMDs (transition metal dichalcogenide). On the other hand, the envisaged scaling scenario for the next 15 years has undergone a significant change recently. While the 2013 ITRS edition required a continuation of aggressive gate length scaling for at least another 15 years, the 2015 edition of the ITRS suggests a deceleration and eventually a levelling off of gate length scaling and puts more emphasis on alternative options such as pitch scaling to keep Moore's Law alive. In the present paper, future CMOS scaling is discussed in the light of emerging two-dimensional MOSFET channel, in particular two-dimensional TMDs. To this end, the scaling scenarios of the 2013 and 2015 ITRS editions are considered and the scaling potential of TMD MOSFETs is investigated by means of quantum-mechanical device simulations. It is shown that for ultimately scaled MOSFETs as required in the 2013 ITRS, the heavy carrier effective masses of the Mo- and W-based TMDs are beneficial for the suppression of direct source-drain tunneling, while to meet the significantly relaxed scaling targets of the 2016 ITRS heavy-effective-mass channels are not needed.

  15. The ultimate security bounds of quantum key distribution protocols

    International Nuclear Information System (INIS)

    Nikolopoulos, G.M.; Alber, G.

    2005-01-01

    Full text: Quantum key distribution (QKD) protocols exploit quantum correlations in order to establish a secure key between two legitimate users. Recent work on QKD has revealed a remarkable link between quantum and secret correlations. In this talk we report on recent results concerning the ultimate upper security bounds of various QKD schemes (i.e., the maximal disturbance up to which the two legitimate users share quantum correlations) under the assumption of general coherent attacks. In particular, we derive an analytic expression for the ultimate upper security bound of QKD schemes that use two mutually unbiased bases. As long as the two legitimate users focus on the sifted key and treat each pair of data independently during the post processing, our results are valid for arbitrary dimensions of the information carriers. The bound we have derived is well below the predictions of optimal cloning machines. The possibility of extraction of a secret key beyond entanglement distillation is also discussed. In the case of qutrits we argue that any eavesdropping strategy is equivalent to a symmetric one. For higher dimensions, however, such equivalence is generally no longer valid. (author)

  16. Ultimate internal pressure capacity assessment of SC structure

    International Nuclear Information System (INIS)

    Park, Hyungkui; Choi, Inkil

    2013-01-01

    An SC structure applied to a containment building can be quite effective. However, an SC structure cannot be applied to a containment building, because its internal pressure resistance performance has not been verified. The containment building, which undergoes ultimate internal pressure, resists the internal pressure through a pre-stress tendon. It is hard to apply a tendon to an SC structure because of its structural characteristics. Therefore, the internal pressure resistance performance of the SC structure itself should be ensured to apply it to a structure with internal pressure resistance. In this study, the suitability of an SC structure as a substitution for the tendon of a pressure resistant structure was evaluated. A containment structure model was used in this study, because it was representative structures that resistance of ultimate internal pressure be required. In this study, a nonlinear analysis was performed to evaluate and compare the behaviors of tendon model and SC structure model. By comparing the internal pressure-displacement according to the structure type, the stability of SC structure model was assessed

  17. Nutrition in adult and childhood cancer: role of carcinogens and anti-carcinogens.

    Science.gov (United States)

    Mosby, Terezie T; Cosgrove, Maeve; Sarkardei, Samiramis; Platt, Karl L; Kaina, Bernd

    2012-10-01

    There is no doubt that diet is one of the main modifiable risk factors for many degenerative diseases, including cancer. More than 30% of adult cancers can be prevented or delayed by diet, being physically active and having a healthy body weight. Plant-based foods, including fruit, vegetables, and whole grains, a favorable omega-6/omega-3 polyunsaturated fatty acids ratio, and fish consumption have a protective effect against cancer. On the contrary, a low intake of fruit and vegetables, high intake of red and processed meat, high intake of sodium, alcohol consumption, a diet rich in refined carbohydrates, and a high intake of total fat may increase risk of cancer. Furthermore, calorie restriction and having a body/mass index on the lower end of the normal range can significantly decrease or delay the onset of cancers. Most studies were performed on adults and thus the role of diet in childhood cancer is less well-understood. In the past, diet was not considered to play any role in its etiology in children. However, nowadays there is a growing body of evidence that prolonged and frequent breastfeeding, the maternal diet during pregnancy and vitamin intake during pregnancy, may impart benefit for reduced cancer risk in children. Usually, decades of healthy dietary habits are needed to see significant difference in cancer risk. Therefore, diet choices and diet preparation starting early in life deserve more attention. Here we review data focusing on which dietary factors, including food-borne carcinogens, affect the onset of cancers in adults and stress out the potential role of diet in childhood cancer prevention.

  18. Evaluation of carcinogenic potential of the herbicide glyphosate, drawing on tumor incidence data from fourteen chronic/carcinogenicity rodent studies.

    Science.gov (United States)

    Greim, Helmut; Saltmiras, David; Mostert, Volker; Strupp, Christian

    2015-03-01

    Abstract Glyphosate, an herbicidal derivative of the amino acid glycine, was introduced to agriculture in the 1970s. Glyphosate targets and blocks a plant metabolic pathway not found in animals, the shikimate pathway, required for the synthesis of aromatic amino acids in plants. After almost forty years of commercial use, and multiple regulatory approvals including toxicology evaluations, literature reviews, and numerous human health risk assessments, the clear and consistent conclusions are that glyphosate is of low toxicological concern, and no concerns exist with respect to glyphosate use and cancer in humans. This manuscript discusses the basis for these conclusions. Most toxicological studies informing regulatory evaluations are of commercial interest and are proprietary in nature. Given the widespread attention to this molecule, the authors gained access to carcinogenicity data submitted to regulatory agencies and present overviews of each study, followed by a weight of evidence evaluation of tumor incidence data. Fourteen carcinogenicity studies (nine rat and five mouse) are evaluated for their individual reliability, and select neoplasms are identified for further evaluation across the data base. The original tumor incidence data from study reports are presented in the online data supplement. There was no evidence of a carcinogenic effect related to glyphosate treatment. The lack of a plausible mechanism, along with published epidemiology studies, which fail to demonstrate clear, statistically significant, unbiased and non-confounded associations between glyphosate and cancer of any single etiology, and a compelling weight of evidence, support the conclusion that glyphosate does not present concern with respect to carcinogenic potential in humans.

  19. Immune regulation by microbiome metabolites.

    Science.gov (United States)

    Kim, Chang H

    2018-03-22

    Commensal microbes and the host immune system have been co-evolved for mutual regulation. Microbes regulate the host immune system, in part, by producing metabolites. A mounting body of evidence indicates that diverse microbial metabolites profoundly regulate the immune system via host receptors and other target molecules. Immune cells express metabolite-specific receptors such as P2X 7 , GPR41, GPR43, GPR109A, aryl hydrocarbon receptor precursor (AhR), pregnane X receptor (PXR), farnesoid X receptor (FXR), TGR5 and other molecular targets. Microbial metabolites and their receptors form an extensive array of signals to respond to changes in nutrition, health and immunological status. As a consequence, microbial metabolite signals contribute to nutrient harvest from diet, and regulate host metabolism and the immune system. Importantly, microbial metabolites bidirectionally function to promote both tolerance and immunity to effectively fight infection without developing inflammatory diseases. In pathogenic conditions, adverse effects of microbial metabolites have been observed as well. Key immune-regulatory functions of the metabolites, generated from carbohydrates, proteins and bile acids, are reviewed in this article. © 2018 John Wiley & Sons Ltd.

  20. Toxicity of acrylamide and its metabolite – Glicydamide

    Directory of Open Access Journals (Sweden)

    Daria Pingot

    2013-04-01

    Full Text Available Acrylamide is a synthetic chemical compound commonly used in many branches of industry. It is mainly used in the synthesis of polyacrylamides, which are widely employed in plastics, paints, varnishes, adhesives and mortars production. Acrylamide is also applied in the cellulose-paper and cosmetic industries to produce toiletries and cosmetics. The interest in acrylamide increased in 2002, when Swedish scientists showed that a considerable amount of this substance is formed during frying and baking of various foods. Studies concerning toxicity of acrylamide and its metabolite - glicydamide showed their neurotoxic, genotoxic and carcinogenic effects. Neverthless, in humans only neurotoxic effect of acrylamide has been clearly evidenced. Genotoxic nature of acetylamide manifests itself mainly in its metabolic conversion to the epoxide derivative glicydamide. Carcinogenic effects of acrylamide have been shown in animal studies. Epidemiological studies have not provided explicit evidence that acrylamide supplied with the diet can initiate the formation of tumors in humans. Acrylamide exposure is assessed by measuring specific compounds (adducts formed during the reaction of acrylamide with hemoglobin and DNA. Med Pr 2013;64(2:259–271

  1. On the ultimate uncertainty of the top quark pole mass

    Energy Technology Data Exchange (ETDEWEB)

    Beneke, M. [Technische Univ. Muenchen, Garching (Germany). Physik-Department; Marquard, P. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Nason, P. [INFN, Sezione di Milano Bicocca (Italy); Steinhauser, M. [Karlsruher Institut fuer Technologie (Germany). Inst. fuer Theoretische Teilchenphysik

    2016-05-15

    We combine the known asymptotic behaviour of the QCD perturbation series expansion, which relates the pole mass of a heavy quark to the MS mass, with the exact series coefficients up to the four-loop order to determine the ultimate uncertainty of the top-quark pole mass due to the renormalon divergence. We perform extensive tests of our procedure by varying the number of colours and flavours, as well as the scale of the strong coupling and the MS mass, and conclude that this uncertainty is around 70 MeV. We further estimate the additional contribution to the mass relation from the five-loop correction and beyond to be 250 MeV.

  2. On the ultimate uncertainty of the top quark pole mass

    International Nuclear Information System (INIS)

    Beneke, M.; Nason, P.; Steinhauser, M.

    2016-05-01

    We combine the known asymptotic behaviour of the QCD perturbation series expansion, which relates the pole mass of a heavy quark to the MS mass, with the exact series coefficients up to the four-loop order to determine the ultimate uncertainty of the top-quark pole mass due to the renormalon divergence. We perform extensive tests of our procedure by varying the number of colours and flavours, as well as the scale of the strong coupling and the MS mass, and conclude that this uncertainty is around 70 MeV. We further estimate the additional contribution to the mass relation from the five-loop correction and beyond to be 250 MeV.

  3. ONE FINANCIAL REPORTING GLOBAL LANGUAGE: THE ULTIMATE GOAL?

    Directory of Open Access Journals (Sweden)

    Amelia Limijaya

    2017-05-01

    Full Text Available This article aims to analyse the extent to which international accounting standards is applied and whether it is the ultimate goal. Up until the end of 2016, approximately there are 84% of the 149 jurisdictions analysed which require IFRS for all or most domestic publicly accountable entities. This may indicate that we are not that much further from having a single set of globally-accepted accounting standards. However, there is more to financial reporting than just accounting standards alone, such as the political aspect of accounting standard-setting, translation issues surrounding IFRS adoption, the US position and the complexity of financial reporting. Improving financial reporting quality needs more than just having global accounting standards, rather, it is also essential to consider the preparers’ incentives and other institutions surrounding the firm. Stakeholders need to broaden the perspective when viewing financial reporting, so that it will not be focused merely on accounting standards alone.

  4. On the ultimate uncertainty of the top quark pole mass

    Science.gov (United States)

    Beneke, M.; Marquard, P.; Nason, P.; Steinhauser, M.

    2017-12-01

    We combine the known asymptotic behaviour of the QCD perturbation series expansion, which relates the pole mass of a heavy quark to the MS ‾ mass, with the exact series coefficients up to the four-loop order to determine the ultimate uncertainty of the top-quark pole mass due to the renormalon divergence. We perform extensive tests of our procedure by varying the number of colours and flavours, as well as the scale of the strong coupling and the MS ‾ mass. Including an estimate of the internal bottom and charm quark mass effect, we conclude that this uncertainty is around 110 MeV. We further estimate the additional contribution to the mass relation from the five-loop correction and beyond to be around 300 MeV.

  5. Multiple (Two) Met Bel 601 In Series Ultimate Vacuum Testing

    Energy Technology Data Exchange (ETDEWEB)

    Restivo, M. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2016-09-30

    SRNL Environmental and Chemical Process Technology (E&CPT) was requested to perform testing of vacuum pumps per a verbal request from the Customer, SRNL Hydrogen Processing Technology. Tritium Operations is currently having difficulties procuring the Normetex™® Model 15 m3/hr (9 CFM) vacuum pump (formerly Normetex Pompes, now EumecaSARL). One possible solution proposed by Hydrogen Processing Technology personnel is to use two Senior Aerospace Metal Bellows MB-601 vacuum pumps piped with the heads in series, and the pumps in series (Figure 1 below). This memorandum documents the ultimate vacuum testing that was performed to determine if this concept was a viable alternate vacuum pump strategy. This testing dovetails with previous pump evaluations documented in references 1 and 2.

  6. Ultimate Drivers and Proximate Correlates of Polyandry in Predatory Mites.

    Directory of Open Access Journals (Sweden)

    Peter Schausberger

    Full Text Available Polyandry is more widespread than anticipated from Bateman's principle but its ultimate (evolutionary causes and proximate (mechanistic correlates are more difficult to pinpoint than those of polygyny. Here, we combined mating experiments, quantification of reproductive traits and microsatellite genotyping to determine the fitness implications of polyandry in two predatory mite species, where males are highly polygynous (up to 45 fertilized females during life, whereas females range from monandry to various polyandry levels. The medium-level polyandrous (up to eight male mates possible Neoseiulus californicus received clear direct and indirect benefits: multiply mated females produced more offspring with higher survival chances over longer times than singly mated females. In contrast, singly and multiply mated females of the low-level polyandrous (commonly two male mates at maximum Phytoseiulus persimilis produced similar numbers of offspring having similar survival chances. In both species, multiple mating resulted in mixed offspring paternities, opening the chance for indirect fitness benefits such as enhanced genetic compatibility, complementarity and/or variability. However, the female re-mating likelihood and the paternity chance of non-first male mates were lower in P. persimilis than in N. californicus. Regarding proximate factors, in both species first mating duration and female re-mating likelihood were negatively correlated. Based on occasional fertilization failure of first male mates in P. persimilis, and mixed offspring paternities in both species, we argue that fertilization assurance and the chance to gain indirect fitness benefits are the ultimate drivers of polyandry in P. persimilis, whereas those of N. californicus are higher offspring numbers coupled with enhanced offspring viability and possibly other indirect fitness benefits. Overall, the adaptive significance and proximate events well reflected the polyandry levels. Our

  7. Ultimate Drivers and Proximate Correlates of Polyandry in Predatory Mites.

    Science.gov (United States)

    Schausberger, Peter; Patiño-Ruiz, J David; Osakabe, Masahiro; Murata, Yasumasa; Sugimoto, Naoya; Uesugi, Ryuji; Walzer, Andreas

    2016-01-01

    Polyandry is more widespread than anticipated from Bateman's principle but its ultimate (evolutionary) causes and proximate (mechanistic) correlates are more difficult to pinpoint than those of polygyny. Here, we combined mating experiments, quantification of reproductive traits and microsatellite genotyping to determine the fitness implications of polyandry in two predatory mite species, where males are highly polygynous (up to 45 fertilized females during life), whereas females range from monandry to various polyandry levels. The medium-level polyandrous (up to eight male mates possible) Neoseiulus californicus received clear direct and indirect benefits: multiply mated females produced more offspring with higher survival chances over longer times than singly mated females. In contrast, singly and multiply mated females of the low-level polyandrous (commonly two male mates at maximum) Phytoseiulus persimilis produced similar numbers of offspring having similar survival chances. In both species, multiple mating resulted in mixed offspring paternities, opening the chance for indirect fitness benefits such as enhanced genetic compatibility, complementarity and/or variability. However, the female re-mating likelihood and the paternity chance of non-first male mates were lower in P. persimilis than in N. californicus. Regarding proximate factors, in both species first mating duration and female re-mating likelihood were negatively correlated. Based on occasional fertilization failure of first male mates in P. persimilis, and mixed offspring paternities in both species, we argue that fertilization assurance and the chance to gain indirect fitness benefits are the ultimate drivers of polyandry in P. persimilis, whereas those of N. californicus are higher offspring numbers coupled with enhanced offspring viability and possibly other indirect fitness benefits. Overall, the adaptive significance and proximate events well reflected the polyandry levels. Our study provides a

  8. The nongenotoxic carcinogens naphthalene and para-dichlorobenzene suppress apoptosis in Caenorhabditis elegans.

    Science.gov (United States)

    Kokel, David; Li, Yehua; Qin, Jun; Xue, Ding

    2006-06-01

    Naphthalene (1) and para-dichlorobenzene (PDCB, 2), which are widely used as moth repellents and air fresheners, cause cancer in rodents and are potential human carcinogens. However, their mechanisms of action remain unclear. Here we describe a novel method for delivering and screening hydrophobic chemicals in C. elegans and apply this technique to investigate the ways in which naphthalene and PDCB may promote tumorigenesis in mammals. We show that naphthalene and PDCB inhibit apoptosis in C. elegans, a result that suggests a cellular mechanism by which these chemicals may promote the survival and proliferation of latent tumor cells. In addition, we find that a naphthalene metabolite directly inactivates caspases by oxidizing the active site cysteine residue; this suggests a molecular mechanism by which these chemicals suppress apoptosis. Naphthalene and PDCB are the first small-molecule apoptosis inhibitors identified in C. elegans. The power of C. elegans molecular genetics, in combination with the possibility of carrying out large-scale chemical screens in this organism, makes C. elegans an attractive and economic animal model for both toxicological studies and drug screens.

  9. Residues of carcinogenic animal drugs in food: difficulties in evaluation of human safety.

    Science.gov (United States)

    Somogyi, A

    1979-01-01

    The indisputable need to intensify animal production in order to provide an adequate food supply for the world population involves the use of substances that are highly potent pharmacologically and toxicologically. The history of regulatory action with regard to such additives is similar to that for other substances: first, no regulation; next, an over-reaction; and now decisions based on judicious evaluation of scientific facts. One factor that differentiates the chemicals used in animal production from other food additives is that both the parent compounds and their metabolites appear in edible products, posing problems both for the analytical detection and safety evaluation of such residues. It would be unrealistic to propose 'zero' tolerances for these additives, even if they are carcinogenic. The benefits gained from drugs that cure and prevent infections and parasitic diseases in food-producing animals, and the fact that analytical methods can now detect very small quantities make the presence of low levels of these substances in food unobjectionable.

  10. Aflatoxin metabolism in humans: detection of metabolites and nucleic acid adducts in urine by affinity chromatography

    International Nuclear Information System (INIS)

    Groopman, J.D.; Donahue, P.R.; Zhu, J.Q.; Chen, J.S.; Wogan, G.N.

    1985-01-01

    A high-affinity IgM monoclonal antibody specific for aflatoxins was covalently bound to Sepharose 4B and used as a preparative column to isolate aflatoxin derivatives from the urine of people and experimental animals who had been exposed to the carcinogen environmentally or under laboratory conditions. Aflatoxin levels were quantified by radioimmunoassay and high-performance liquid chromatography after elution from the affinity column. In studies on rats injected with [ 14 C]aflatoxin B1, the authors identified the major aflatoxin-DNA adduct, 2,3-dihydro-2-(N7-guanyl)-3-hydroxy-aflatoxin B1 (AFB1-N7-Gua), and the oxidative metabolites M1 and P1 as the major aflatoxin species present in the urine. When this methodology was applied to human urine samples obtained from people from the Guangxi Province of China exposed to aflatoxin B1 through dietary contamination, the aflatoxin metabolites detected were also AFB1-N7-Gua and aflatoxins M1 and P1. Therefore, affinity chromatography using a monoclonal antibody represents a useful and rapid technique with which to isolate this carcinogen and its metabolites in biochemical epidemiology and for subsequent quantitative measurements, providing exposure information that can be used for risk assessment

  11. A Review of the Carcinogenic Potential of Bisphenol A

    Science.gov (United States)

    Seachrist, Darcie D; Bonk, Kristen W.; Ho, Shuk-Mei; Prins, Gail S.; Soto, Ana M.; Keri, Ruth A.

    2015-01-01

    The estrogenic properties of bisphenol A (BPA), a ubiquitous synthetic monomer that can leach into the food and water supply, have prompted considerable research into exposure-associated health risks in humans. Endocrine-disrupting properties of BPA suggest it may impact developmental plasticity during early life, predisposing individuals to disease at doses below the oral reference dose (RfD) established by the Environmental Protection Agency in 1982. Herein, we review the current in vivo literature evaluating the carcinogenic properties of BPA. We conclude that there is substantial evidence from rodent studies indicating that early-life BPA exposures below the RfD lead to increased susceptibility to mammary and prostate cancer. Based on the definitions of “carcinogen” put forth by the International Agency for Research on Cancer and the National Toxicology Program, we propose that BPA may be reasonably anticipated to be a human carcinogen in the breast and prostate due to its tumor promoting properties. PMID:26493093

  12. Retraction: Evaluation of Carcinogenic Effects of Electromagnetic Fields (Emf

    Directory of Open Access Journals (Sweden)

    Bakir Mehic

    2010-08-01

    Full Text Available This retracts the article "EVALUATION OF CARCINOGENIC EFFECTS OF ELECTROMAGNETIC FIELDS (EMF" on page 245. The Editor-in-chief of the Bosnian Journal ofBasic Medical Sciences has decided to retract the article from Bayazit V et al. [1] entitled as: “Evaluation of carcinogenic effects of electromagnetic fields (EMF” published in Bosn J Basic Med Sci. 2010 Aug;10(3:245-50.After the editorial office was alerted of possible plagiarism in the article, it conducted thorough investigation and concluded that the article apparently represents plagiarized material from two World Health Organization reports, one European Commission report and other sources. Since this is considered scientific plagiarism and scientific misconduct, Editor-in-chief has decided to withdraw the article. The authors have agreed with the editorial office decision.

  13. Systematic network assessment of the carcinogenic activities of cadmium

    International Nuclear Information System (INIS)

    Chen, Peizhan; Duan, Xiaohua; Li, Mian; Huang, Chao; Li, Jingquan; Chu, Ruiai; Ying, Hao; Song, Haiyun; Jia, Xudong; Ba, Qian; Wang, Hui

    2016-01-01

    Cadmium has been defined as type I carcinogen for humans, but the underlying mechanisms of its carcinogenic activity and its influence on protein-protein interactions in cells are not fully elucidated. The aim of the current study was to evaluate, systematically, the carcinogenic activity of cadmium with systems biology approaches. From a literature search of 209 studies that performed with cellular models, 208 proteins influenced by cadmium exposure were identified. All of these were assessed by Western blotting and were recognized as key nodes in network analyses. The protein-protein functional interaction networks were constructed with NetBox software and visualized with Cytoscape software. These cadmium-rewired genes were used to construct a scale-free, highly connected biological protein interaction network with 850 nodes and 8770 edges. Of the network, nine key modules were identified and 60 key signaling pathways, including the estrogen, RAS, PI3K-Akt, NF-κB, HIF-1α, Jak-STAT, and TGF-β signaling pathways, were significantly enriched. With breast cancer, colorectal and prostate cancer cellular models, we validated the key node genes in the network that had been previously reported or inferred form the network by Western blotting methods, including STAT3, JNK, p38, SMAD2/3, P65, AKT1, and HIF-1α. These results suggested the established network was robust and provided a systematic view of the carcinogenic activities of cadmium in human. - Highlights: • A cadmium-influenced network with 850 nodes and 8770 edges was established. • The cadmium-rewired gene network was scale-free and highly connected. • Nine modules were identified, and 60 key signaling pathways related to cadmium-induced carcinogenesis were found. • Key mediators in the network were validated in multiple cellular models.

  14. Carcinogenicity of chromium and chemoprevention: a brief update

    Directory of Open Access Journals (Sweden)

    Wang Y

    2017-08-01

    Full Text Available Yafei Wang,1,* Hong Su,1,* Yuanliang Gu,1 Xin Song,1 Jinshun Zhao1,2 1Department of Preventative Medicine, Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, People’s Republic of China; 2Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA *These authors contributed equally to this work Abstract: Chromium has two main valence states: hexavalent chromium (Cr[VI] and trivalent chromium (Cr[III]. Cr(VI, a well-established human carcinogen, can enter cells by way of a sulfate/phosphate anion-transport system, and then be reduced to lower-valence intermediates consisting of pentavalent chromium (Cr[V], tetravalent chromium (Cr[IV] or Cr(III via cellular reductants. These intermediates may directly or indirectly result in DNA damage or DNA–protein cross-links. Although Cr(III complexes cannot pass easily through cell membranes, they have the ability to accumulate around cells to induce cell-surface morphological alteration and result in cell-membrane lipid injuries via disruption of cellular functions and integrity, and finally to cause DNA damage. In recent years, more research, including in vitro, in vivo, and epidemiological studies, has been conducted to evaluate the genotoxicity/carcinogenicity induced by Cr(VI and/or Cr(III compounds. At the same time, various therapeutic agents, especially antioxidants, have been explored through in vitro and in vivo studies for preventing chromium-induced genotoxicity/carcinogenesis. This review aims to provide a brief update on the carcinogenicity of Cr(VI and Cr(III and chemoprevention with different antioxidants. Keywords: hexavalent chromium, Cr(VI, trivalent chromium, Cr(III, genotoxicity, carcinogenicity, chemoprevention, antioxidant 

  15. Mammalian cell transformation: Mechanisms of carcinogenesis and assays for carcinogens

    International Nuclear Information System (INIS)

    Barrett, J.C.; Tennant, R.W.

    1985-01-01

    This book contains nine sections, each consisting of several papers. The section titles are: Molecular Changes in Cell Transformation; Differentiation, Growth Control, and Cell Transformation; Mutagenesis and Cell Transformation; Tumor Promotion and Cell Transformation; Mechanisms of Transformation of Human Fibroblasts; Mechanisms of Transformation of Epithelial Cells; Mechanisms of C 3 H 10T12 Cell Transformation; Mechanisms of Radiation-Induced Cell Transformation; and Use of Cell Transformation Assays for Carcinogen Testing

  16. Risk assessment of nickel carcinogenicity and occupational lung cancer.

    OpenAIRE

    Shen, H M; Zhang, Q F

    1994-01-01

    Recent progress in risk assessment of nickel carcinogenicity and its correlation with occupational lung cancer in nickel-exposed workers is reviewed. Epidemiological investigations provide reliable data indicating the close relation between nickel exposure and high lung cancer risk, especially in nickel refineries. The nickel species-specific effects and the dose-response relationship between nickel exposure and lung cancer are among the main questions that are explored extensively. It is als...

  17. Carcinogenic activity of polycyclic hydrocarbons on man and animals

    Energy Technology Data Exchange (ETDEWEB)

    Shabad, L M

    1976-03-01

    Basic facts are reported on the carcinogenic activity of polycyclic aromatic hydrocarbons (PAH) towards humans and animals. Benzyprene (BP) is taken as a standard indicator for PAH. Studies of the distribution of BP in atmosphere, hydrosphere, in soil, in plants, and in animals led to an understanding of the accumulation and breakdown of this chemical. On this basis, safety limits were set as a prophylactic measure.

  18. Systematic network assessment of the carcinogenic activities of cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Peizhan; Duan, Xiaohua; Li, Mian; Huang, Chao [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Li, Jingquan; Chu, Ruiai; Ying, Hao; Song, Haiyun [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); Jia, Xudong [Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); Ba, Qian, E-mail: qba@sibs.ac.cn [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); Wang, Hui, E-mail: huiwang@sibs.ac.cn [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); School of Life Science and Technology, ShanghaiTech University, Shanghai (China)

    2016-11-01

    Cadmium has been defined as type I carcinogen for humans, but the underlying mechanisms of its carcinogenic activity and its influence on protein-protein interactions in cells are not fully elucidated. The aim of the current study was to evaluate, systematically, the carcinogenic activity of cadmium with systems biology approaches. From a literature search of 209 studies that performed with cellular models, 208 proteins influenced by cadmium exposure were identified. All of these were assessed by Western blotting and were recognized as key nodes in network analyses. The protein-protein functional interaction networks were constructed with NetBox software and visualized with Cytoscape software. These cadmium-rewired genes were used to construct a scale-free, highly connected biological protein interaction network with 850 nodes and 8770 edges. Of the network, nine key modules were identified and 60 key signaling pathways, including the estrogen, RAS, PI3K-Akt, NF-κB, HIF-1α, Jak-STAT, and TGF-β signaling pathways, were significantly enriched. With breast cancer, colorectal and prostate cancer cellular models, we validated the key node genes in the network that had been previously reported or inferred form the network by Western blotting methods, including STAT3, JNK, p38, SMAD2/3, P65, AKT1, and HIF-1α. These results suggested the established network was robust and provided a systematic view of the carcinogenic activities of cadmium in human. - Highlights: • A cadmium-influenced network with 850 nodes and 8770 edges was established. • The cadmium-rewired gene network was scale-free and highly connected. • Nine modules were identified, and 60 key signaling pathways related to cadmium-induced carcinogenesis were found. • Key mediators in the network were validated in multiple cellular models.

  19. Bignoniaceae Metabolites as Semiochemicals

    Directory of Open Access Journals (Sweden)

    Lucía Castillo

    2010-10-01

    Full Text Available Members of the family Bignoniaceae are mostly found in tropical and neo-tropical regions in America, Asia and Africa, although some of them are cultivated in other regions as ornamentals. Species belonging to this family have been extensively studied in regard to their pharmacological properties (as extracts and isolated compounds. The aim of this review is to summarize the reported scientific evidence about the chemical properties as well as that of the extracts and isolated compounds from species of this family, focusing mainly in insect-plant interactions. As it is known, this family is recognized for the presence of iridoids which are markers of oviposition and feeding preference to species which have became specialist feeders. Some herbivore species have also evolved to the point of been able to sequester iridoids and use them as defenses against their predators. However, iridoids also exhibit anti-insect properties, and therefore they may be good lead molecules to develop botanical pesticides. Other secondary metabolites, such as quinones, and whole extracts have also shown potential as anti-insect agents.

  20. Use of short-term test systems for the prediction of the hazard represented by potential chemical carcinogens

    International Nuclear Information System (INIS)

    Glass, L.R.; Jones, T.D.; Easterly, C.E.; Walsh, P.J.

    1990-10-01

    It has been hypothesized that results from short-term bioassays will ultimately provide information that will be useful for human health hazard assessment. Historically, the validity of the short-term tests has been assessed using the framework of the epidemiologic/medical screens. In this context, the results of the carcinogen (long-term) bioassay is generally used as the standard. However, this approach is widely recognized as being biased and, because it employs qualitative data, cannot be used to assist in isolating those compounds which may represent a more significant toxicologic hazard than others. In contrast, the goal of this research is to address the problem of evaluating the utility of the short-term tests for hazard assessment using an alternative method of investigation. Chemicals were selected mostly from the list of carcinogens published by the International Agency for Research on Carcinogens (IARC); a few other chemicals commonly recognized as hazardous were included. Tumorigenicity and mutagenicity data on 52 chemicals were obtained from the Registry of Toxic Effects of Chemical Substances (RTECS) and were analyzed using a relative potency approach. The data were evaluated in a format which allowed for a comparison of the ranking of the mutagenic relative potencies of the compounds (as estimated using short-term data) vs. the ranking of the tumorigenic relative potencies (as estimated from the chronic bioassays). Although this was a preliminary investigation, it offers evidence that the short-term tests systems may be of utility in ranking the hazards represented by chemicals which may contribute to increased carcinogenesis in humans as a result of occupational or environmental exposures. 177 refs., 8 tabs

  1. Use of short-term test systems for the prediction of the hazard represented by potential chemical carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Glass, L.R.; Jones, T.D.; Easterly, C.E.; Walsh, P.J.

    1990-10-01

    It has been hypothesized that results from short-term bioassays will ultimately provide information that will be useful for human health hazard assessment. Historically, the validity of the short-term tests has been assessed using the framework of the epidemiologic/medical screens. In this context, the results of the carcinogen (long-term) bioassay is generally used as the standard. However, this approach is widely recognized as being biased and, because it employs qualitative data, cannot be used to assist in isolating those compounds which may represent a more significant toxicologic hazard than others. In contrast, the goal of this research is to address the problem of evaluating the utility of the short-term tests for hazard assessment using an alternative method of investigation. Chemicals were selected mostly from the list of carcinogens published by the International Agency for Research on Carcinogens (IARC); a few other chemicals commonly recognized as hazardous were included. Tumorigenicity and mutagenicity data on 52 chemicals were obtained from the Registry of Toxic Effects of Chemical Substances (RTECS) and were analyzed using a relative potency approach. The data were evaluated in a format which allowed for a comparison of the ranking of the mutagenic relative potencies of the compounds (as estimated using short-term data) vs. the ranking of the tumorigenic relative potencies (as estimated from the chronic bioassays). Although this was a preliminary investigation, it offers evidence that the short-term tests systems may be of utility in ranking the hazards represented by chemicals which may contribute to increased carcinogenesis in humans as a result of occupational or environmental exposures. 177 refs., 8 tabs.

  2. Future Synchrotron Light Sources Based on Ultimate Storage Rings

    International Nuclear Information System (INIS)

    Cai, Yunhai

    2012-01-01

    The main purpose of this talk is to describe how far one might push the state of the art in storage ring design. The talk will start with an overview of the latest developments and advances in the design of synchrotron light sources based on the concept of an 'ultimate' storage ring. The review will establish how bright a ring based light source might be, where the frontier of technological challenges are, and what the limits of accelerator physics are. Emphasis will be given to possible improvements in accelerator design and developments in technology toward the goal of achieving an ultimate storage ring. An ultimate storage ring (USR), defined as an electron ring-based light source having an emittance in both transverse planes at the diffraction limit for the range of X-ray wavelengths of interest for a scientific community, would provide very high brightness photons having high transverse coherence that would extend the capabilities of X-ray imaging and probe techniques beyond today's performance. It would be a cost-effective, high-coherence 4th generation light source, competitive with one based on energy recovery linac (ERL) technology, serving a large number of users studying material, chemical, and biological sciences. Furthermore, because of the experience accumulated over many decades of ring operation, it would have the great advantage of stability and reliability. In this paper we consider the design of an USR having 10-pm-rad emittance. It is a tremendous challenge to design a storage ring having such an extremely low emittance, a factor of 100 smaller than those in existing light sources, especially such that it has adequate dynamic aperture and beam lifetime. In many ultra-low emittance designs, the injection acceptances are not large enough for accumulation of the electron beam, necessitating on-axis injection where stored electron bunches are completely replaced with newly injected ones. Recently, starting with the MAX-IV 7-bend achromatic cell, we

  3. Future Synchrotron Light Sources Based on Ultimate Storage Rings

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Yunhai; /SLAC

    2012-04-09

    The main purpose of this talk is to describe how far one might push the state of the art in storage ring design. The talk will start with an overview of the latest developments and advances in the design of synchrotron light sources based on the concept of an 'ultimate' storage ring. The review will establish how bright a ring based light source might be, where the frontier of technological challenges are, and what the limits of accelerator physics are. Emphasis will be given to possible improvements in accelerator design and developments in technology toward the goal of achieving an ultimate storage ring. An ultimate storage ring (USR), defined as an electron ring-based light source having an emittance in both transverse planes at the diffraction limit for the range of X-ray wavelengths of interest for a scientific community, would provide very high brightness photons having high transverse coherence that would extend the capabilities of X-ray imaging and probe techniques beyond today's performance. It would be a cost-effective, high-coherence 4th generation light source, competitive with one based on energy recovery linac (ERL) technology, serving a large number of users studying material, chemical, and biological sciences. Furthermore, because of the experience accumulated over many decades of ring operation, it would have the great advantage of stability and reliability. In this paper we consider the design of an USR having 10-pm-rad emittance. It is a tremendous challenge to design a storage ring having such an extremely low emittance, a factor of 100 smaller than those in existing light sources, especially such that it has adequate dynamic aperture and beam lifetime. In many ultra-low emittance designs, the injection acceptances are not large enough for accumulation of the electron beam, necessitating on-axis injection where stored electron bunches are completely replaced with newly injected ones. Recently, starting with the MAX-IV 7-bend

  4. Efficiency Of Different Teaching Models In Teaching Of Frisbee Ultimate

    Directory of Open Access Journals (Sweden)

    Žuffová Zuzana

    2015-05-01

    Full Text Available The aim of the study was to verify the efficiency of two frisbee ultimate teaching models at 8-year grammar schools relative to age. In the experimental group was used a game based model (Teaching Games for Understanding and in the control group the traditional model based on teaching techniques. 6 groups of female students took part in experiment: experimental group 1 (n=10, age=11.6, experimental group 2 (n=12, age=13.8, experimental group 3 (n=14, age =15.8, control group 1 (n=11, age =11.7, control group 2 (n=10, age =13.8 and control group 3 (n=9, age =15.8. Efficiency of the teaching models was evaluated based of game performance and special knowledge results. Game performance was evaluated by the method of game performance assessment based on GPAI (Game Performance Assessment Instrument through video record. To verify level of knowledge, we used a knowledge test, which consisted of questions related to the rules and tactics knowledge of frisbee ultimate. To perform statistical evaluation Mann-Whitney U-test was used. Game performance assessment and knowledge level indicated higher efficiency of TGfU in general, but mostly statistically insignificant. Experimental groups 1 and 2 were significantly better in the indicator that evaluates tactical aspect of game performance - decision making (p<0.05. Experimental group 3 was better in the indicator that evaluates skill execution - disc catching. The results showed that the students of the classes taught by game based model reached partially better game performance in general. Experimental groups achieved from 79.17 % to 80 % of correct answers relating to the rules and from 75 % to 87.5 % of correct answers relating to the tactical knowledge in the knowledge test. Control groups achieved from 57.69 % to 72.22 % of correct answers relating to the rules and from 51.92 % to 72.22 % of correct answers relating to the tactical knowledge in the knowledge test.

  5. Mechanisms of Enzyme-Catalyzed Reduction of Two Carcinogenic Nitro-Aromatics, 3-Nitrobenzanthrone and Aristolochic Acid I: Experimental and Theoretical Approaches

    Directory of Open Access Journals (Sweden)

    Marie Stiborová

    2014-06-01

    Full Text Available This review summarizes the results found in studies investigating the enzymatic activation of two genotoxic nitro-aromatics, an environmental pollutant and carcinogen 3-nitrobenzanthrone (3-NBA and a natural plant nephrotoxin and carcinogen aristolochic acid I (AAI, to reactive species forming covalent DNA adducts. Experimental and theoretical approaches determined the reasons why human NAD(PH:quinone oxidoreductase (NQO1 and cytochromes P450 (CYP 1A1 and 1A2 have the potential to reductively activate both nitro-aromatics. The results also contributed to the elucidation of the molecular mechanisms of these reactions. The contribution of conjugation enzymes such as N,O-acetyltransferases (NATs and sulfotransferases (SULTs to the activation of 3-NBA and AAI was also examined. The results indicated differences in the abilities of 3-NBA and AAI metabolites to be further activated by these conjugation enzymes. The formation of DNA adducts generated by both carcinogens during their reductive activation by the NOQ1 and CYP1A1/2 enzymes was investigated with pure enzymes, enzymes present in subcellular cytosolic and microsomal fractions, selective inhibitors, and animal models (including knock-out and humanized animals. For the theoretical approaches, flexible in silico docking methods as well as ab initio calculations were employed. The results summarized in this review demonstrate that a combination of experimental and theoretical approaches is a useful tool to study the enzyme-mediated reaction mechanisms of 3-NBA and AAI reduction.

  6. Mechanisms of Enzyme-Catalyzed Reduction of Two Carcinogenic Nitro-Aromatics, 3-Nitrobenzanthrone and Aristolochic Acid I: Experimental and Theoretical Approaches

    Science.gov (United States)

    Stiborová, Marie; Frei, Eva; Schmeiser, Heinz H.; Arlt, Volker M.; Martínek, Václav

    2014-01-01

    This review summarizes the results found in studies investigating the enzymatic activation of two genotoxic nitro-aromatics, an environmental pollutant and carcinogen 3-nitrobenzanthrone (3-NBA) and a natural plant nephrotoxin and carcinogen aristolochic acid I (AAI), to reactive species forming covalent DNA adducts. Experimental and theoretical approaches determined the reasons why human NAD(P)H:quinone oxidoreductase (NQO1) and cytochromes P450 (CYP) 1A1 and 1A2 have the potential to reductively activate both nitro-aromatics. The results also contributed to the elucidation of the molecular mechanisms of these reactions. The contribution of conjugation enzymes such as N,O-acetyltransferases (NATs) and sulfotransferases (SULTs) to the activation of 3-NBA and AAI was also examined. The results indicated differences in the abilities of 3-NBA and AAI metabolites to be further activated by these conjugation enzymes. The formation of DNA adducts generated by both carcinogens during their reductive activation by the NOQ1 and CYP1A1/2 enzymes was investigated with pure enzymes, enzymes present in subcellular cytosolic and microsomal fractions, selective inhibitors, and animal models (including knock-out and humanized animals). For the theoretical approaches, flexible in silico docking methods as well as ab initio calculations were employed. The results summarized in this review demonstrate that a combination of experimental and theoretical approaches is a useful tool to study the enzyme-mediated reaction mechanisms of 3-NBA and AAI reduction. PMID:24918288

  7. New perspectives on the cancer risks of trichloroethylene, its metabolites, and chlorination by-products

    Energy Technology Data Exchange (ETDEWEB)

    Bogen, K.T. [Lawrence Livermore National Lab., CA (United States); Slone, T.; Gold, L.S.; Manley, N.; Revzan, K. [Lawrence Berkeley Lab., CA (United States)

    1994-12-08

    Scientific developments in the 1990`s have important implications for the assessment of cancer risks posed by exposures to trichloroethylene (TCE). These new developments include: epidemiological studies; experimental studies of TCE carcinogenicity, metabolism and metabolite carcinogenicity; applications of new physiologically based pharmacokinetic (PBPK) models for TCE; and new pharmacodynamic data obtained for TCE and its rhetabolites. Following a review of previous assessments of TCE carcinogenicity, each of these new sets of developments is summarized. The new epidemiological data do not provide evidence of TCE carcinogenicity in humans, and the new pharmacodynamic data support the hypothesis that TCE carcinogenicity is caused by TCE-induced cytotoxicity. Based on this information, PBPK-based estimates for likely no-adverse effect levels (NOAELs) for human exposures to TCE are calculated to be 16 ppb for TCE in air respired 24 hr/day, and 210 ppb for TCE in drinking water. Cancer risks of zero are predicted for TCE exposures below these calculated NOAELs. For comparison, hypothetical cancer risks posed by lifetime ingestive and multiroute household exposures to TCE in drinking water, at the currently enforced Maximum Contaminant Level (MCL) concentration of 5 ppb are extrapolated from animal bioassay data using a conservative, linear dose-response model. These TCE-related risks are compared to corresponding ones associated with concentrations of chlorination by-products (CBP) in household water. It is shown that, from the standpoint of comparative hypothetical cancer risks, based on conservative linear dose-response extrapolations, there would likely be no health benefit, and more likely a possible health detriment, associated with any switch from a household water supply containing <375 ppb TCE to one containing CBP at levels corresponding to the currently proposed 80-ppb MCL for total trihalomethanes.

  8. Process Inherent Ultimate Safety (PIUS) reactor evaluation study: Final report

    International Nuclear Information System (INIS)

    1987-02-01

    This report presents the results of an independent study by United Engineers and Constructors (UNITED) of the SECURE-P Process Inherent Ultimate Safety (PIUS) Reactor Concept which is presently under development by the Swedish light water reactor vendor ASEA-ATOM of Vasteras, Sweden. This study was performed to investigate whether there is any realistic basis for believing that the PIUS reactor could be a viable competitor in the US energy market in the future. Assessments were limited to the technical, economic and licensing aspects of PIUS. Socio-political issues, while certainly important in answering this question, are so broad and elusive that it was considered that addressing them with the limited perspective of one small group from one company would be of questionable value and likely be misleading. Socio-political issues aside, the key issue is economics. For this reason, the specific objectives of this study were to determine if the estimated PIUS plant cost will be competitive in the US market and to identify and evaluate the technical and licensing risks that might make PIUS uneconomical or otherwise unacceptable

  9. ZIO: The Ultimate Linux I/O Framework

    CERN Document Server

    Gonzalez Cobas, J D; Rubini, A; Nellaga, S; Vaga, F

    2014-01-01

    ZIO (with Z standing for “The Ultimate I/O” Framework) was developed for CERN with the specific needs of physics labs in mind, which are poorly addressed in the mainstream Linux kernel. ZIO provides a framework for industrial, high-bandwith, high-channel count I/O device drivers (digitizers, function generators, timing devices like TDCs) with performance, generality and scalability as design goals. Among its features, it offers abstractions for • both input and output channels, and channel sets • run-time selection of trigger types • run-time selection of buffer types • sysfs-based configuration • char devices for data and metadata • a socket interface (PF ZIO) as alternative to char devices In this paper, we discuss the design and implementation of ZIO, and describe representative cases of driver development for typical and exotic applications: drivers for the FMC (FPGAMezzanine Card, see [1]) boards developed at CERN like the FMC ADC 100Msps digitizer, FMC TDC timestamp counter, and FMC DEL ...

  10. Episodic foresight and anxiety: Proximate and ultimate perspectives.

    Science.gov (United States)

    Miloyan, Beyon; Bulley, Adam; Suddendorf, Thomas

    2016-03-01

    In this paper, we examine the relationship between episodic foresight and anxiety from an evolutionary perspective, proposing that together they confer an advantage for modifying present moment decision-making and behaviour in the light of potential future threats to fitness. We review the body of literature on the role of episodic foresight in anxiety, from both proximate and ultimate perspectives. We propose that anxious feelings associated with episodic simulation of possible threat-related future events serve to imbue these simulations with motivational currency. Episodic and semantic details of a future threat may be insufficient for motivating its avoidance, but anxiety associated with a simulation can provoke adaptive threat management. As such, we detail how anxiety triggered by a self-generated, threat-related future simulation prepares the individual to manage that threat (in terms of its likelihood and/or consequences) over greater temporal distances than observed in other animals. We then outline how anxiety subtypes may represent specific mechanisms for predicting and managing particular classes of fitness threats. This approach offers an inroad for understanding the nature of characteristic future thinking patterns in anxiety disorders and serves to illustrate the adaptive function of the mechanism from which clinical anxiety deviates. © 2015 The British Psychological Society.

  11. Yield, utilization, storage and ultimate storage of depleted uranium

    International Nuclear Information System (INIS)

    Aumueller, L.; Hermann, J.

    1977-11-01

    More than 80% of the uranium leaving uranium enrichment plants is depleted to a residual content of about 0,25% U 235. Due to the present ineconomical further depletion to the technically possible residual content of 0,1% U 235, the so-called 'tails' are first of all stored. The quantity of stored depleted uranium in the FRG should be about 100.000 t by the year 2000. It represents a strategic reserve for future energy supply regardless of profitableness. The study analysis the conceivable possible uses for the tails quantity considered. These are, besides further depletion whose profitableness is considered, also the use as breeder material in breeder reactors and the use in the non-nuclear field. The main part of the study deals with the various storage possibilities of the depleted uranium in oxidic or fluoride form. A comparison of costs of alternative storage concepts showed a clear advantage for the storage of UF 6 in 48 inch containers already in use. The conceivable accidents in storing are analyzed and measures to reduce the consequences are discussed. Finally, the problems of ultimate storage for the remaining waste after further depletion or use are investigated and the costs arising here are also estimated. (RB) [de

  12. Optimized molten salt receivers for ultimate trough solar fields

    Science.gov (United States)

    Riffelmann, Klaus-J.; Richert, Timo; Kuckelkorn, Thomas

    2016-05-01

    Today parabolic trough collectors are the most successful concentrating solar power (CSP) technology. For the next development step new systems with increased operation temperature and new heat transfer fluids (HTF) are currently developed. Although the first power tower projects have successfully been realized, up to now there is no evidence of an all-dominant economic or technical advantage of power tower or parabolic trough. The development of parabolic trough technology towards higher performance and significant cost reduction have led to significant improvements in competitiveness. The use of molten salt instead of synthetic oil as heat transfer fluid will bring down the levelized costs of electricity (LCOE) even further while providing dispatchable energy with high capacity factors. FLABEG has developed the Ultimate TroughTM (UT) collector, jointly with sbp Sonne GmbH and supported by public funds. Due to its validated high optical accuracy, the collector is very suitable to operate efficiently at elevated temperatures up to 550 °C. SCHOTT will drive the key-innovations by introducing the 4th generation solar receiver that addresses the most significant performance and cost improvement measures. The new receivers have been completely redesigned to provide a product platform that is ready for high temperature operation up to 550 °C. Moreover distinct product features have been introduced to reduce costs and risks in solar field assembly and installation. The increased material and design challenges incurred with the high temperature operation have been reflected in sophisticated qualification and validation procedures.

  13. Accounting conservatism,ultimate ownership and investment efficiency

    Institute of Scientific and Technical Information of China (English)

    Xiaodong Xu; Xia Wang; Nina Han

    2012-01-01

    Purpose-The purpose of this paper is to analyze and examine the role of accounting conservatism on firm investment behavior in China.Design/methodology/approach-By combining a developed theoretical framework and empirical study,this paper examines the impacts of accounting conservatism on firm investment.The sample and data are all collected from Wind and CAMAR databases.Findings-The paper finds that the association between accounting conservatism and capital expenditure is significantly positive when inside capital is not enough to use for investment,suggesting that conservatism can expend the level of investment by decreasing information asymmetry and cost of capital;however,the association between accounting conservatism and capital expenditure is significantly negative when inside capital is enough to use for investment,suggesting that conservatism can curtail the level of investment by mitigating the interest conflicts between management and outside shareholders and decreasing agency costs.Additionally,the paper finds that the severity of information asymmetry and agency problem affects the role of accounting conservatism on firm investment behaviour,and the association between accounting conservatism and capital expenditure is weaker for firms with ultimate ownership controller as local government or individuals.Originality/value-This is the first paper to analyze and examine the impacts of accounting conservatism on firm investment in China directly.The findings are also useful to explain the awkward predicament found by prior literature.

  14. Ultimate storage of radioactive wastes annual report, 1973

    International Nuclear Information System (INIS)

    The present report is a cooperative effort by the Company for Radiation and Environmental Research, Munich, and the Company for Nuclear Research, Karlsruhe, and provides a survey of work carried out during 1973 in the area of ultimate storage of radioactive wastes. Mining and construction works which were carried out in the Asse Salt Mine near Remlingen both underground as well as above the ground and which were used for repair, maintenance and expansion of the operation consistent with its future tasks are reported. The storage of low-level wastes at the 750 m level and also the test-oriented storage of medium-level waste materials at the 490 m level were carried out within the reporting period. Shielded storage casks S7V developed by the GfK were used for the first time in September for transporting 200 l iron-hooped drums filled with medium-level radioactive wastes to Asse, each shipment always containing seven drums. With two round-trips a week taking place between the Nuclear Research Center, Karlsruhe and the Asse II shaft installation, 14 drums were brought each week so that, by the end of the year, the quantity in storage amounted to a total of 233 drums. Further information is provided concerning the present status of research work in the fields of oromechanics, geology and hydrology as well as other findings. Further, storage techniques are discussed which are presently in the planning stage

  15. Thermal performance measurements on ultimate heat sinks--cooling ponds

    International Nuclear Information System (INIS)

    Hadlock, R.K.; Abbey, O.B.

    1977-12-01

    The primary objective of the studies described is to obtain the requisite data, with respect to modeling requirements, to characterize thermal performance of heat sinks for nuclear facilities existing at elevated water temperatures in result of experiencing a genuinely large heat load and responding to meteorological influence. The data should reflect thermal performance for combinations leading to worst-case meteorological influence. A geothermal water retention basin has been chosen as the site for the first measurement program and data have been obtained in the first of several experiments scheduled to be performed there. These data illustrate the thermal and water budgets during episodes of cooling from an initially high pond water bulk temperature. Monitoring proceeded while the pond experienced only meteorological and seepage influence. The data are discussed and are presented as a data volume which may be used for calculation purposes. Suggestions for future measurement programs are stated with the intent to maintain and improve relevance to nuclear ultimate heat sinks while continuing to examine the performance of the analog geothermal pond. It is further suggested that the geothermal pond, with some modification, may be a suitable site for spray pond measurements

  16. Exploring Ultimate Water Capillary Evaporation in Nanoscale Conduits.

    Science.gov (United States)

    Li, Yinxiao; Alibakhshi, Mohammad Amin; Zhao, Yihong; Duan, Chuanhua

    2017-08-09

    Capillary evaporation in nanoscale conduits is an efficient heat/mass transfer strategy that has been widely utilized by both nature and mankind. Despite its broad impact, the ultimate transport limits of capillary evaporation in nanoscale conduits, governed by the evaporation/condensation kinetics at the liquid-vapor interface, have remained poorly understood. Here we report experimental study of the kinetic limits of water capillary evaporation in two dimensional nanochannels using a novel hybrid channel design. Our results show that the kinetic-limited evaporation fluxes break down the limits predicated by the classical Hertz-Knudsen equation by an order of magnitude, reaching values up to 37.5 mm/s with corresponding heat fluxes up to 8500 W/cm 2 . The measured evaporation flux increases with decreasing channel height and relative humidity but decreases as the channel temperature decreases. Our findings have implications for further understanding evaporation at the nanoscale and developing capillary evaporation-based technologies for both energy- and bio-related applications.

  17. Expression of a fms-related oncogene in carcinogen-induced neoplastic epithelial cells

    International Nuclear Information System (INIS)

    Walker, C.; Nettesheim, P.; Barrett, J.C.; Gilmer, T.M.

    1987-01-01

    Following carcinogen exposure in vitro, normal rat tracheal epithelial cells are transformed in a multistage process in which the cultured cells become immortal and ultimately, neoplastic. Five cell lines derived from tumors produced by neoplastically transformed rat tracheal epithelial cells were examined for the expression of 11 cellular oncogenes previously implicated in pulmonary or epithelial carcinogenesis. RNA homologous to fms was expressed at a level 5-19 times higher than normal tracheal epithelial cells in three of five of the tumor-derived lines. All three lines expressing high levels of fms-related RNA gave rise to invasive tumors of epithelial origin when injected into nude mice. Increased expression of the fms-related mRNA was not due to gene amplification, and no gene rearrangement was detected by Southern analyses. RNA blot analysis using a 3' v-fms probe detected a 9.5-kilobase message in the three tumor-derived lines, whereas both normal rat aveolar macrophages and the human choriocarcinoma line BeWo expressed a fms transcript of ≅ 4 kilobases. The authors conclude from these data that the gene expressed as a 9.5-kilobase transcript in these neoplastic epithelial cells is a member of a fms-related gene family but may be distinct from the gene that encodes the macrophage colony-stimulating factor (CSF-1) receptor

  18. Secondary metabolites from marine microorganisms.

    Science.gov (United States)

    Kelecom, Alphonse

    2002-03-01

    After 40 years of intensive research, chemistry of marine natural products has become a mature field. Since 1995, there are signals of decreased interest in the search of new metabolites from traditional sources such as macroalgae and octocorals, and the number of annual reports on marine sponges stabilized. On the contrary, metabolites from microorganisms is a rapidly growing field, due, at least in part, to the suspicion that a number of metabolites obtained from algae and invertebrates may be produced by associated microorganisms. Studies are concerned with bacteria and fungi, isolated from seawater, sediments, algae, fish and mainly from marine invertebrates such as sponges, mollusks, tunicates, coelenterates and crustaceans. Although it is still to early to define tendencies, it may be stated that the metabolites from microorganisms are in most cases quite different from those produced by the invertebrate hosts. Nitrogenated metabolites predominate over acetate derivatives, and terpenes are uncommon. Among the latter, sesquiterpenes, diterpenes and carotenes have been isolated; among nitrogenated metabolites, amides, cyclic peptides and indole alkaloids predominate.

  19. Secondary metabolites from marine microorganisms

    Directory of Open Access Journals (Sweden)

    KELECOM ALPHONSE

    2002-01-01

    Full Text Available After 40 years of intensive research, chemistry of marine natural products has become a mature field. Since 1995, there are signals of decreased interest in the search of new metabolites from traditional sources such as macroalgae and octocorals, and the number of annual reports on marine sponges stabilized. On the contrary, metabolites from microorganisms is a rapidly growing field, due, at least in part, to the suspicion that a number of metabolites obtained from algae and invertebrates may be produced by associated microorganisms. Studies are concerned with bacteria and fungi, isolated from seawater, sediments, algae, fish and mainly from marine invertebrates such as sponges, mollusks, tunicates, coelenterates and crustaceans. Although it is still to early to define tendencies, it may be stated that the metabolites from microorganisms are in most cases quite different from those produced by the invertebrate hosts. Nitrogenated metabolites predominate over acetate derivatives, and terpenes are uncommon. Among the latter, sesquiterpenes, diterpenes and carotenes have been isolated; among nitrogenated metabolites, amides, cyclic peptides and indole alkaloids predominate.

  20. Diuron metabolites and urothelial cytotoxicity: In vivo, in vitro and molecular approaches

    International Nuclear Information System (INIS)

    Da Rocha, Mitscheli S.; Arnold, Lora L.; Dodmane, Puttappa R.; Pennington, Karen L.; Qiu, Fang; De Camargo, João Lauro V.; Cohen, Samuel M.

    2013-01-01

    Diuron is carcinogenic to the rat urinary bladder at high dietary levels. The proposed mode of action (MOA) for diuron is urothelial cytotoxicity and necrosis followed by regenerative urothelial hyperplasia. Diuron-induced urothelial cytotoxicity is not due to urinary solids. Diuron is extensively metabolized, and in rats, N-(3,4-dichlorophenyl)urea (DCPU) and 4,5-dichloro-2-hydroxyphenyl urea (2-OH-DCPU) were the predominant urinary metabolites; lesser metabolites included N-(3,4-dichlorophenyl)-3-methylurea (DCPMU) and trace levels of 3,4-dichloroaniline (DCA). In humans, DCPMU and DCPU have been found in the urine after a case of product abuse. To aid in elucidating the MOA of diuron and to evaluate the metabolites that are responsible for the diuron toxicity in the bladder epithelium, we investigated the urinary concentrations of metabolites in male Wistar rats treated with 2500 ppm of diuron, the urothelial cytotoxicity in vitro of the metabolites and their gene expression profiles. DCPU was found in rat urine at concentrations substantially greater than the in vitro IC50 and induced more gene expression alterations than the other metabolites tested. 2-OH-DCPU was present in urine at a concentration approximately half of the in vitro IC50, whereas DCPMU and DCA were present in urine at concentrations well below the IC50. For the diuron-induced MOA for the rat bladder, we suggest that DCPU is the primary metabolite responsible for the urothelial cytotoxicity with some contribution also by 2-OH-DCPU. This study supports a MOA for diuron-induced bladder effects in rats consisting of metabolism to DCPU (and 2-OH-DCPU to a lesser extent), concentration and excretion in urine, urothelial cytotoxicity, and regenerative proliferation

  1. Diuron metabolites and urothelial cytotoxicity: in vivo, in vitro and molecular approaches.

    Science.gov (United States)

    Da Rocha, Mitscheli S; Arnold, Lora L; Dodmane, Puttappa R; Pennington, Karen L; Qiu, Fang; De Camargo, João Lauro V; Cohen, Samuel M

    2013-12-15

    Diuron is carcinogenic to the rat urinary bladder at high dietary levels. The proposed mode of action (MOA) for diuron is urothelial cytotoxicity and necrosis followed by regenerative urothelial hyperplasia. Diuron-induced urothelial cytotoxicity is not due to urinary solids. Diuron is extensively metabolized, and in rats, N-(3,4-dichlorophenyl)urea (DCPU) and 4,5-dichloro-2-hydroxyphenyl urea (2-OH-DCPU) were the predominant urinary metabolites; lesser metabolites included N-(3,4-dichlorophenyl)-3-methylurea (DCPMU) and trace levels of 3,4-dichloroaniline (DCA). In humans, DCPMU and DCPU have been found in the urine after a case of product abuse. To aid in elucidating the MOA of diuron and to evaluate the metabolites that are responsible for the diuron toxicity in the bladder epithelium, we investigated the urinary concentrations of metabolites in male Wistar rats treated with 2500ppm of diuron, the urothelial cytotoxicity in vitro of the metabolites and their gene expression profiles. DCPU was found in rat urine at concentrations substantially greater than the in vitro IC50 and induced more gene expression alterations than the other metabolites tested. 2-OH-DCPU was present in urine at a concentration approximately half of the in vitro IC50, whereas DCPMU and DCA were present in urine at concentrations well below the IC50. For the diuron-induced MOA for the rat bladder, we suggest that DCPU is the primary metabolite responsible for the urothelial cytotoxicity with some contribution also by 2-OH-DCPU. This study supports a MOA for diuron-induced bladder effects in rats consisting of metabolism to DCPU (and 2-OH-DCPU to a lesser extent), concentration and excretion in urine, urothelial cytotoxicity, and regenerative proliferation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. Genotoxicity and potential carcinogenicity of cyanobacterial toxins - a review.

    Science.gov (United States)

    Zegura, Bojana; Straser, Alja; Filipič, Metka

    2011-01-01

    The occurrence of cyanobacterial blooms has increased significantly in many regions of the world in the last century due to water eutrophication. These blooms are hazardous to humans, animals, and plants due to the production of cyanotoxins, which can be classified in five different groups: hepatotoxins, neurotoxins, cytotoxins, dermatotoxins, and irritant toxins (lipopolysaccharides). There is evidence that certain cyanobacterial toxins are genotoxic and carcinogenic; however, the mechanisms of their potential carcinogenicity are not well understood. The most frequently occurring and widespread cyanotoxins in brackish and freshwater blooms are the cyclic heptapeptides, i.e., microcystins (MCs), and the pentapeptides, i.e., nodularins (NODs). The main mechanism associated with potential carcinogenic activity of MCs and NOD is the inhibition of protein phosphatases, which leads to the hyperphosphorylation of cellular proteins, which is considered to be associated with their tumor-promoting activity. Apart from this, MCs and NOD induce increased formation of reactive oxygen species and, consequently, oxidative DNA damage. There is also evidence that MCs and NOD induce micronuclei, and NOD was shown to have aneugenic activity. Both cyanotoxins interfere with DNA damage repair pathways, which, along with DNA damage, is an important factor involved in the carcinogenicity of these agents. Furthermore, these toxins increase the expression of TNF-α and early-response genes, including proto-oncogenes, genes involved in the response to DNA damage, cell cycle arrest, and apoptosis. Rodent studies indicate that MCs and NOD are tumor promotors, whereas NOD is thought to have also tumor-initiating activity. Another cyanobacterial toxin, cylindrospermopsin (CYN), which has been neglected for a long time, is lately being increasingly found in the freshwater environment. The principal mechanism of its toxicity is the irreversible inhibition of protein synthesis. It is pro

  3. Nicotine, Carcinogen, and Toxin Exposure in Long-Term E-Cigarette and Nicotine Replacement Therapy Users: A Cross-sectional Study.

    Science.gov (United States)

    Shahab, Lion; Goniewicz, Maciej L; Blount, Benjamin C; Brown, Jamie; McNeill, Ann; Alwis, K Udeni; Feng, June; Wang, Lanqing; West, Robert

    2017-03-21

    Given the rapid increase in the popularity of e-cigarettes and the paucity of associated longitudinal health-related data, the need to assess the potential risks of long-term use is essential. To compare exposure to nicotine, tobacco-related carcinogens, and toxins among smokers of combustible cigarettes only, former smokers with long-term e-cigarette use only, former smokers with long-term nicotine replacement therapy (NRT) use only, long-term dual users of both combustible cigarettes and e-cigarettes, and long-term users of both combustible cigarettes and NRT. Cross-sectional study. United Kingdom. The following 5 groups were purposively recruited: combustible cigarette-only users, former smokers with long-term (≥6 months) e-cigarette-only or NRT-only use, and long-term dual combustible cigarette-e-cigarette or combustible cigarette-NRT users (n = 36 to 37 per group; total n = 181). Sociodemographic and smoking characteristics were assessed. Participants provided urine and saliva samples and were analyzed for biomarkers of nicotine, tobacco-specific N-nitrosamines (TSNAs), and volatile organic compounds (VOCs). After confounders were controlled for, no clear between-group differences in salivary or urinary biomarkers of nicotine intake were found. The e-cigarette-only and NRT-only users had significantly lower metabolite levels for TSNAs (including the carcinogenic metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL]) and VOCs (including metabolites of the toxins acrolein; acrylamide; acrylonitrile; 1,3-butadiene; and ethylene oxide) than combustible cigarette-only, dual combustible cigarette-e-cigarette, or dual combustible cigarette-NRT users. The e-cigarette-only users had significantly lower NNAL levels than all other groups. Combustible cigarette-only, dual combustible cigarette-NRT, and dual combustible cigarette-e-cigarette users had largely similar levels of TSNA and VOC metabolites. Cross-sectional design with self-selected sample. Former

  4. IARC monographs: 40 years of evaluating carcinogenic hazards to humans.

    Science.gov (United States)

    Pearce, Neil; Blair, Aaron; Vineis, Paolo; Ahrens, Wolfgang; Andersen, Aage; Anto, Josep M; Armstrong, Bruce K; Baccarelli, Andrea A; Beland, Frederick A; Berrington, Amy; Bertazzi, Pier Alberto; Birnbaum, Linda S; Brownson, Ross C; Bucher, John R; Cantor, Kenneth P; Cardis, Elisabeth; Cherrie, John W; Christiani, David C; Cocco, Pierluigi; Coggon, David; Comba, Pietro; Demers, Paul A; Dement, John M; Douwes, Jeroen; Eisen, Ellen A; Engel, Lawrence S; Fenske, Richard A; Fleming, Lora E; Fletcher, Tony; Fontham, Elizabeth; Forastiere, Francesco; Frentzel-Beyme, Rainer; Fritschi, Lin; Gerin, Michel; Goldberg, Marcel; Grandjean, Philippe; Grimsrud, Tom K; Gustavsson, Per; Haines, Andy; Hartge, Patricia; Hansen, Johnni; Hauptmann, Michael; Heederik, Dick; Hemminki, Kari; Hemon, Denis; Hertz-Picciotto, Irva; Hoppin, Jane A; Huff, James; Jarvholm, Bengt; Kang, Daehee; Karagas, Margaret R; Kjaerheim, Kristina; Kjuus, Helge; Kogevinas, Manolis; Kriebel, David; Kristensen, Petter; Kromhout, Hans; Laden, Francine; Lebailly, Pierre; LeMasters, Grace; Lubin, Jay H; Lynch, Charles F; Lynge, Elsebeth; 't Mannetje, Andrea; McMichael, Anthony J; McLaughlin, John R; Marrett, Loraine; Martuzzi, Marco; Merchant, James A; Merler, Enzo; Merletti, Franco; Miller, Anthony; Mirer, Franklin E; Monson, Richard; Nordby, Karl-Cristian; Olshan, Andrew F; Parent, Marie-Elise; Perera, Frederica P; Perry, Melissa J; Pesatori, Angela Cecilia; Pirastu, Roberta; Porta, Miquel; Pukkala, Eero; Rice, Carol; Richardson, David B; Ritter, Leonard; Ritz, Beate; Ronckers, Cecile M; Rushton, Lesley; Rusiecki, Jennifer A; Rusyn, Ivan; Samet, Jonathan M; Sandler, Dale P; de Sanjose, Silvia; Schernhammer, Eva; Costantini, Adele Seniori; Seixas, Noah; Shy, Carl; Siemiatycki, Jack; Silverman, Debra T; Simonato, Lorenzo; Smith, Allan H; Smith, Martyn T; Spinelli, John J; Spitz, Margaret R; Stallones, Lorann; Stayner, Leslie T; Steenland, Kyle; Stenzel, Mark; Stewart, Bernard W; Stewart, Patricia A; Symanski, Elaine; Terracini, Benedetto; Tolbert, Paige E; Vainio, Harri; Vena, John; Vermeulen, Roel; Victora, Cesar G; Ward, Elizabeth M; Weinberg, Clarice R; Weisenburger, Dennis; Wesseling, Catharina; Weiderpass, Elisabete; Zahm, Shelia Hoar

    2015-06-01

    Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans. The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process to determine the validity of these concerns. Here, we present the results of that examination, review the history of IARC evaluations, and describe how the IARC evaluations are performed. We concluded that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various disciplines and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed. The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.

  5. Ultimate strength of a large wind turbine blade

    Energy Technology Data Exchange (ETDEWEB)

    Moelholt Jensen, Find

    2008-05-15

    of the profile, also called 'local deformations', to verify a more complex response than that of a Bernoulli-Euler Beam. A large number of mechanical displacement sensors and strain gauges were mounted inside and outside the structure. These measurements further proved highly useful when validating Finite Element based analysis and failure mechanisms should be decided. Finally, comparisons of the ultimate failure loads observed in the full-scale tests are presented and conclusions are drawn based on the mechanisms found. (au)

  6. Ultimate resistance of a reinforced concrete foundation under impulsive loading

    International Nuclear Information System (INIS)

    Aquaro, D.; Forasassi, G.; Marconi, M.

    2003-01-01

    The impact of a spent nuclear fuel cask against a reinforced concrete slab of a temporary repository for spent nuclear fuel is numerically analysed. The analysis considers accidental events in which a spent nuclear fuel cask would drop against the floor of a repository during lifting operations. Two types of solutions have been taken into account: a simple reinforced concrete structure and a structure provided with a 40 mm thick steel liner on the impacted surface, connected to a 1600 mm thick concrete bed. The model is assumed to be axisymmetric and positioned on an elastic ground (Winkler model). The concrete has been simulated as: elastic perfectly plastic under compressive stresses limited by a crushing strain; elastic linear under tensile stresses until a cracking stress value and a following decrease of stress characterized by a constant or variable softening modulus; limited ability to resist at shear stresses after cracking characterized by a shear retention factor. The steel of the reinforcement bars and of the cask has been simulated as an elastic perfectly plastic material. Several numerical simulations have been performed in order to determine the influence, on the ultimate resistance of the structure under examination, of the steel liner, of some characteristic parameters of concrete (as the softening module and the shear retention factor) and of the Winkler coefficient values, simulating the elastic behaviour of the ground. The obtained results demonstrate that a steel liner produces a lower stress in the concrete as well as in the reinforcement but the bed is still subjected to the cracking phenomenon throughout its entire width although the crushing is localized to only a few elements near the impact zone. The use of a more complex constitutive equation for the concrete considering the shear retention factor and the softening module has given results which do not differ greatly from those related to a more simplified model. A different degree of

  7. Evaluation of the carcinogenic risks at the influence of POPs.

    Science.gov (United States)

    Nazhmetdinova, Aiman; Kassymbayev, Adlet; Chalginbayeva, Altinay

    2017-12-20

    Kazakhstan is included in the list of environmentally vulnerable countries and Kyzylorda oblast in particular. This is due to its geographical, spatial and temporal and socioeconomic features. As part of the program "Integrated approaches in the management of public health in the Aral region", we have carried out an expertise on many samples of natural environments and products. Samples were selected in accordance with sampling procedures according to regulatory documents by specialists of the Pesticide Toxicology Laboratory. It is accredited by the State Standard of the Republic of Kazakhstan, for compliance with ST RK ISO/IEC 17025-2007 "General requirements for the competence of test and calibration laboratories". Gas chromatograph was used for the determination of residues of organochlorine pesticides. For the determination of dioxins, polychlorinated biphenyl was conducted on the gas chromatomass spectrometer with quadruple detector produce by Agilent Company, USA. To assess the risk, we carried out the mathematical calculations according to the risk of chemicals polluting (No P 2.1.10.1920-04, Russia). Calculation of the carcinogenic risk was carried out with the use of data on the size of the exposure and meanings of carcinogenic potential factors (slope factor and unit risk). The evaluation of persistent organic pollutants (POPs), based on the previous results of the research concerning water, soil and food products, was held in five population settlements in Kyzylorda oblast villages: Ayteke bi, Zhalagash, Zhosaly, Shieli and Aralsk town. Pollution with the POPs in the environmental objects by means of exposition and evaluation of the carcinogenic risk to human health is confirmed by the data of the statistical reporting about some morbidity in Kyzylorda oblast, such as skin diseases and subcutaneous tissue, endocrine system diseases, pregnancy complications etc. The received levels of carcinogenic risks, which were first carried out in the Republic of

  8. Keishibukuryogan is not carcinogenic in Sprague-Dawley rats

    OpenAIRE

    Kanitani, Masanao; Nishimura, Nobuo; Edamoto, Hiroshi; Kase, Yoshio

    2016-01-01

    Keishibukuryogan is a traditional Japanese medicine widely administered to patients with menopausal symptoms. Because humans use it on a long-term basis, we believed that a carcinogenicity study was warranted. We orally administered keishibukuryogan (TJ-25) extract powder to 6-week-old Sprague-Dawley rats [Crl:CD(SD)], which were divided into four dosage groups-0 (water for injection), 100, 500 and 2,500 mg/kg/day for 24 months. We found that TJ-25 did not affect the survival rate of either s...

  9. Carcinogenic Substances Naturrally Occuring in the Human Diet

    Directory of Open Access Journals (Sweden)

    Mogos Viorel T.

    2018-03-01

    Full Text Available Oncogenesis is a result of the combined action of numerous factors peculiar to the body and the environment (the latter are more effective. Among dietary factors directly implied in the occurrence of malignant tumors we can mention: food additives, contaminated food, polycyclic aromatic hydrocarbons, nitrosamines and some components which are naturally present in food. Moreover, food-related malignancies are a consequence of the increased consumption of fats, proteins, alcohol in parallel with decreases in the consumption of dietary fibers and some micronutrients. Carcinogenic substances naturally present in food are of a particular interest for both nutritionist’s and patient’s, usually not being perceived as being harmful.

  10. DNA adduct formation by the ubiquitous environmental pollutant 3-nitrobenzanthrone and its metabolites in rats

    International Nuclear Information System (INIS)

    Arlt, Volker M.; Sorg, Bernd L.; Osborne, Martin; Hewer, Alan; Seidel, Albrecht; Schmeiser, Heinz H.; Phillips, David H.

    2003-01-01

    Diesel exhaust is known to induce tumours in animals and is suspected of being carcinogenic in humans. Of the compounds found in diesel exhaust, 3-nitrobenzanthrone (3-NBA) is an extremely potent mutagen and suspected human carcinogen forming multiple DNA adducts in vitro. 3-Aminobenzanthrone (3-ABA), 3-acetylaminobenzanthrone (3-Ac-ABA), and N-acetyl-N-hydroxy-3-aminobenzanthrone (N-Ac-N-OH-ABA) were identified as 3-NBA metabolites. In order to gain insight into the pathways of metabolic activation leading to 3-NBA-derived DNA adducts we treated Wistar rats intraperitoneally with 2 mg/kg body weight of 3-NBA, 3-ABA, 3-Ac-ABA, or N-Ac-N-OH-ABA and compared DNA adducts present in different organs. With each compound either four or five DNA adduct spots were detected by TLC in all tissues examined (lung, liver, kidney, heart, pancreas, and colon) using the nuclease P1 or butanol enrichment version of the 32 P-postlabelling method, respectively. Using HPLC co-chromatographic analysis we showed that all major 3-NBA-DNA adducts produced in vivo in rats are derived from reductive metabolites bound to purine bases and lack an N-acetyl group. Our results indicate that 3-NBA metabolites (3-ABA, 3-Ac-ABA and N-Ac-N-OH-ABA) undergo several biotransformations and that N-hydroxy-3-aminobenzanthrone (N-OH-ABA) appears to be the common intermediate in 3-NBA-derived DNA adduct formation. Therefore, 3-NBA-DNA adducts are useful biomarkers for exposure to 3-NBA and its metabolites and may help to identify enzymes involved in their metabolic activation

  11. Results of screening NCI/NTP nongenotoxic carcinogens and genotoxic noncarcinogens with the ke test

    International Nuclear Information System (INIS)

    Mendelsohn, M.L.; Bakale, G.; McCreary, R.D.

    1989-01-01

    The interdependence of the electrophilic and carcinogenic properties of chemicals that was demonstrated two decades ago rekindled interest in the somatic mutation theory of carcinogenesis. Interest in this theory grew with the development of a reverse-mutation bacterial assay in the laboratory of B.N. Ames that permitted the mutagenic properties of the chemicals to be determined quickly and yielded results which indicated that ''carcinogens are mutagens.'' Subsequent validation studies of this bioassay, the Salmonella typhimurium/microsome or ''Ames test,'' by Ames' group and others provided additional support for the correlation between mutagenicity and carcinogenicity which led to the worldwide deployment of the Ames test in thousands of laboratories and to the development of more than 100 other short-term tests that continue to be used to identify potential carcinogens via various end-points of genotoxicity. This document discusses electrophilicity, mutagenicity, and carcinogenicity relationships as well as carcinogen-screening of chemicals. 28 refs., 4 tabs

  12. Prevalence of occupational exposure to carcinogens among workers of Arabic, Chinese and Vietnamese ancestry in Australia.

    Science.gov (United States)

    Boyle, Terry; Carey, Renee N; Glass, Deborah C; Peters, Susan; Fritschi, Lin; Reid, Alison

    2015-09-01

    Although job-related diseases result in more deaths per year than job-related injuries, most research concerning ethnic minority workers has concerned accidents and injuries rather than disease-causing exposures such as carcinogens. We conducted a telephone-based cross-sectional survey to estimate the prevalence of occupational exposure to carcinogens among a sample of ethnic minority workers in Australia, and compared their exposure prevalence to that of a sample of the general Australian-born working population ('Australian workers'). One-third of the ethnic minority workers were exposed to at least one carcinogen at work. The likelihood of exposure to carcinogens was not significantly different from that of Australian workers, although the likelihood of exposure to individual carcinogens varied by ethnicity. Knowing the prevalence of exposure to carcinogens in the workplace in different ethnic groups will allow better targeted and informed occupational health and safety measures to be implemented where necessary. © 2015 Wiley Periodicals, Inc.

  13. Mode of carcinogenic action of pesticides inducing thyroid follicular cell tumors in rodents.

    OpenAIRE

    Hurley, P M

    1998-01-01

    Of 240 pesticides screened for carcinogenicity by the U.S. Environmental Protection Agency Office of Pesticide Programs, at least 24 (10%) produce thyroid follicular cell tumors in rodents. Thirteen of the thyroid carcinogens also induce liver tumors, mainly in mice, and 9 chemicals produce tumors at other sites. Some mutagenic data are available on all 24 pesticides producing thyroid tumors. Mutagenicity does not seem to be a major determinant in thyroid carcinogenicity, except for possibly ...

  14. Determination of Urinary PAH Metabolites Using DLLME Hyphenated to Injector Port Silylation and GC-MS-MS.

    Science.gov (United States)

    Gupta, Manoj Kumar; Jain, Rajeev; Singh, Pratibha; Ch, Ratnasekhar; Mudiam, Mohana Krishna Reddy

    2015-06-01

    Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants and well-known carcinogens. Hydroxy derivatives of PAH are considered as biomarkers of PAH exposure, and there is a need to measure these metabolites at low concentrations. So, a precise and eco-friendly analytical method has been developed for rapid determination of PAH metabolites. For the first time, a new analytical method based on coupling of dispersive liquid-liquid microextraction (DLLME) with auto-injector port silylation (auto-IPS) followed by gas chromatography-tandem mass spectrometry (GC-MS-MS) analysis is reported for the analysis of seven urinary PAH metabolites. Factors affecting DLLME and IPS, such as type and volume of extraction and disperser solvent, pH, ionic strength, injector port temperature, volume of N,O-bis(trimethylsilyl)trifluoroacetamide and type of solvent were investigated. Under optimized conditions, the limit of detection and limit of quantification were found to be in the range of 1-9 and 3-29 ng/mL, respectively. Satisfactory recoveries of metabolites in urine samples in the range of 87-95% were found. The developed method has been successfully applied for the determination of PAH metabolites in urine samples of exposed workers. DLLME-auto-IPS-GC-MS-MS method is time, labor, solvent and reagent saving, which can be routinely used for the analysis of urinary PAH metabolites. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Evidence supporting product standards for carcinogens in smokeless tobacco products.

    Science.gov (United States)

    Hatsukami, Dorothy K; Stepanov, Irina; Severson, Herb; Jensen, Joni A; Lindgren, Bruce R; Horn, Kimberly; Khariwala, Samir S; Martin, Julia; Carmella, Steven G; Murphy, Sharon E; Hecht, Stephen S

    2015-01-01

    Smokeless tobacco products sold in the United States vary significantly in yields of nicotine and tobacco-specific nitrosamines (TSNA). With the passage of the Family Smoking Prevention and Tobacco Control Act, the Food and Drug Administration now has the authority to establish product standards. However, limited data exist determining the relative roles of pattern of smokeless tobacco use versus constituent levels in the smokeless tobacco product in exposure of users to carcinogens. In this study, smokeless tobacco users of brands varying in nicotine and TSNA content were recruited from three different regions in the U.S. Participants underwent two assessment sessions. During these sessions, demographic and smokeless tobacco use history information along with urine samples to assess biomarkers of exposure and effect were collected. During the time between data collection, smokeless tobacco users recorded the amount and duration of smokeless tobacco use on a daily basis using their diary cards. Results showed that independent of pattern of smokeless tobacco use and nicotine yields, levels of TSNA in smokeless tobacco products played a significant role in carcinogen exposure levels. Product standards for reducing levels of TSNA in smokeless tobacco products are necessary to decrease exposure to these toxicants and potentially to reduce risk for cancer. ©2014 American Association for Cancer Research.

  16. Polyamines modulate carcinogen-induced mutagenesis in vivo.

    Science.gov (United States)

    Wallon, U Margaretha; O'Brien, Thomas G

    2005-01-01

    Elevated polyamine levels as a consequence of targeted overexpression of ornithine decarboxylase (ODC) to murine skin enhance susceptibility to tumorigenesis in this tissue. A possible mechanism for the enhanced susceptibility phenotype is an increased sensitivity of tissues with elevated polyamine levels to the mutagenic action of carcinogens. To test this hypothesis, a transgenic mouse model containing the Big Blue transgene and also expressing a K6/ODC transgene was developed. Incorporation of the K6/ODC transgene into the Big Blue model did not affect the spontaneous lacI mutant frequency in either skin or epidermis of the double-transgenic mice. After skin treatment with single doses of either 7,12-dimethylbenz[a]anthracene or N-methyl-N'-nitro-N-nitrosoguanidine, however, the mutant frequency was significantly increased in the skin of double-transgenic Big Blue;K6/ODC mice compared to Big Blue controls. The increases in mutant frequency were clearly due to ODC transgene activity, since treatment of mice with the ODC inhibitor, alpha-difluoromethylornithine, completely abolished the difference in mutant frequencies between double-transgenic and Big Blue mice. These results demonstrate that intracellular polyamine levels modulate mutation induction following carcinogen exposure. 2004 Wiley-Liss, Inc.

  17. Carcinogen specific dosimetry model for passive smokers of various ages

    International Nuclear Information System (INIS)

    Robinson, Risa J.

    2005-01-01

    Studies indicate that being exposed to second hand smoke increases the chance of developing lung cancer. Understanding the deposition of carcinogenic particles present in second hand smoke is necessary to understand the development of specific histologic type cancers. In this study, a deposition model is presented for subjects of various ages exposed to sidestream smoke. The model included particle dynamics of coagulation, hygroscopic growth, charge and cloud behavior. Concentrations were varied from the maximum measured indoor concentrations (10 6 particles/cm 3 ) to what would be expected from wisps of smoke (10 8 particles/cm 3 ). Model results agreed well with experimental data taken from human subject deposition measurements (four studies). The model results were used to determine the dose intensity (dose per unit airway surface area) of Benzo[a]pyrene (BaP) in the respiratory tract for subjects of various ages. Model predictions for BaP surface concentration on the airway walls paralleled incident rates of tumors by location in the upper tracheobronchial region. Mass deposition efficiency was found to be larger for younger subjects, consistent with diffusion being the predominant mechanism for this particle size range. However, the actual dose intensity of BaP was found to be smaller for children than adults. This occurred due to the predominant effect of the smaller initial inhaled mass for children resulting from smaller tidal volumes. The resulting model is a useful tool to predict carcinogen specific particle deposition

  18. Carcinogenic action of polycyclic hydrocarbons in animals and man

    Energy Technology Data Exchange (ETDEWEB)

    Shabad, L M

    1976-01-01

    Polycyclic hydrocarbons are universally present in the atmosphere, soil, lakes and streams, vegetation, and human and animal tissues, the concentrations varying with distance from the sources (heating systems, industrial plants, automobile highways and airports, petroleum refineries, etc.). The most potent of the carcinogens is benz(a)pyrene whose presence in an object, as shown by studies done in the author's laboratory, is an indication that other polycyclic hydrocarbons are also present. These studies also demonstrated that while benz(a)pyrene may accumulate in soil with seasonal fluctuations, it can also be destroyed by certain microorganisms. Other experiments showed that benz(a)pyrene and other such compounds can be destroyed in tissue culture as well as in vivo (e.g., benz(a)pyrene given to cows with fodder was found in their milk but not in meat after they were slaughtered). It is suggested that maximum permissible concentrations be set for benz(a)pyrene in air and water to minimize its potential carcinogenic effects.

  19. Carcinogenicity of a medicinal ozokerite and its constituents

    Energy Technology Data Exchange (ETDEWEB)

    Ruchkovskii, B; Borisiuk, I P; Tiktin, L A

    1970-01-01

    Fluorimetric analysis and skin painting tests on mice demonstrated that ceresin (a medicinal ozokerite) contains carcinogens. In the USSR, ceresin is applied to the skin or rectal and vaginal mucosa for the treatment of a variety of diseases. Ceresin and its components were tested on 460 male non-inbred mice (aged 2 to 2.5 mo) by applying either the melted substance or a 60% benzene solution of it to the skin in 30-mg doses (2 admin./week x 10 mo). Skin papillomas were produced after latent periods of 4.5 to 9 mo by paraffin, petrolatum, heavy mineral oil and 1/2 ceresin samples. Squamous cell carcinomas of the skin were seen in 2 mice painted with mineral oil. Fluorimetric analysis of ceresin demonstrated several polycyclic hydrocarbons, identified as 3,4-benzpyrene (BP) benzo(ghi) perylene, and perylene. An aqueous extract of crude ozokerite contained traces of BP, while a benzene extract contained 70 to 77 microg/kg. It is recommended that petroleum products which are commonly used to improve the consistency of ceresin be analyzed for the presence of carcinogens before use.

  20. Induction of prophage lambda by chlorinated organics: Detection of some single-species/single-site carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    DeMarini, D.M.; Brooks, H.G. (Environmental Protection Agency, Research Triangle Park, NC (United States))

    1992-01-01

    Twenty-eight chlorinated organic compounds were evaluated for their ability to induce DNA damage using the Microscreen prophage-induction assay in Escherichia coli. Comparison of the performance characteristics of the prophage-induction and Salmonella assays to rodent carcinogenicity assays showed that the prophage-induction assay had a somewhat higher specificity than did the Salmonella assay (70% vs. 50%); sensitivity, concordance, and positive and negative predictivity were similar for the two microbial assays. The Microscreen prophage-induction assay failed to detect eight carcinogens, perhaps due to toxicity or other unknown factors; five of these eight carcinogens were detected by the Salmonella assay. However, the prophage-induction assay did detect six carcinogens that were not detected by the Salmonella assay, and five of these were single-species, single-site carcinogens, mostly mouse liver carcinogens. Some of these carcinogens, such as the chloroethanes, produce free radicals, which may be the basis for their carcinogenicity and ability to induce prophage. The prophage-induction (or other SOS) assay may be useful in identifying some genotoxic chlorinated carcinogens that induce DNA damage that do not revert the standard Salmonella tester strains.

  1. Potential carcinogenicity predicted by computational toxicity evaluation of thiophosphate pesticides using QSTR/QSCarciAR model.

    Science.gov (United States)

    Petrescu, Alina-Maria; Ilia, Gheorghe

    2017-07-01

    This study presents in silico prediction of toxic activities and carcinogenicity, represented by the potential carcinogenicity DSSTox/DBS, based on vector regression with a new Kernel activity, and correlating the predicted toxicity values through a QSAR model, namely: QSTR/QSCarciAR (quantitative structure toxicity relationship/quantitative structure carcinogenicity-activity relationship) described by 2D, 3D descriptors and biological descriptors. The results showed a connection between carcinogenicity (compared to the structure of a compound) and toxicity, as a basis for future studies on this subject, but each prediction is based on structurally similar compounds and the reactivation of the substructures of these compounds.

  2. Predicting carcinogenicity of diverse chemicals using probabilistic neural network modeling approaches

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Kunwar P., E-mail: kpsingh_52@yahoo.com [Academy of Scientific and Innovative Research, Council of Scientific and Industrial Research, New Delhi (India); Environmental Chemistry Division, CSIR-Indian Institute of Toxicology Research, Post Box 80, Mahatma Gandhi Marg, Lucknow 226 001 (India); Gupta, Shikha; Rai, Premanjali [Academy of Scientific and Innovative Research, Council of Scientific and Industrial Research, New Delhi (India); Environmental Chemistry Division, CSIR-Indian Institute of Toxicology Research, Post Box 80, Mahatma Gandhi Marg, Lucknow 226 001 (India)

    2013-10-15

    Robust global models capable of discriminating positive and non-positive carcinogens; and predicting carcinogenic potency of chemicals in rodents were developed. The dataset of 834 structurally diverse chemicals extracted from Carcinogenic Potency Database (CPDB) was used which contained 466 positive and 368 non-positive carcinogens. Twelve non-quantum mechanical molecular descriptors were derived. Structural diversity of the chemicals and nonlinearity in the data were evaluated using Tanimoto similarity index and Brock–Dechert–Scheinkman statistics. Probabilistic neural network (PNN) and generalized regression neural network (GRNN) models were constructed for classification and function optimization problems using the carcinogenicity end point in rat. Validation of the models was performed using the internal and external procedures employing a wide series of statistical checks. PNN constructed using five descriptors rendered classification accuracy of 92.09% in complete rat data. The PNN model rendered classification accuracies of 91.77%, 80.70% and 92.08% in mouse, hamster and pesticide data, respectively. The GRNN constructed with nine descriptors yielded correlation coefficient of 0.896 between the measured and predicted carcinogenic potency with mean squared error (MSE) of 0.44 in complete rat data. The rat carcinogenicity model (GRNN) applied to the mouse and hamster data yielded correlation coefficient and MSE of 0.758, 0.71 and 0.760, 0.46, respectively. The results suggest for wide applicability of the inter-species models in predicting carcinogenic potency of chemicals. Both the PNN and GRNN (inter-species) models constructed here can be useful tools in predicting the carcinogenicity of new chemicals for regulatory purposes. - Graphical abstract: Figure (a) shows classification accuracies (positive and non-positive carcinogens) in rat, mouse, hamster, and pesticide data yielded by optimal PNN model. Figure (b) shows generalization and predictive

  3. A proposed framework for consistent regulation of public exposures to radionuclides and other carcinogens

    International Nuclear Information System (INIS)

    Kocher, D.C.; Hoffman, F.O.

    1991-01-01

    This paper discusses a proposed framework for consistent regulation of carcinogenic risks to the public based on establishing de manifestis (i.e., unacceptable) and de minimis (i.e., trivial) lifetime risks from exposure to any carcinogens at levels of about 10 -1 --10 -3 and 10 -4 --10 -6 , respectively, and reduction of risks above de minimis levels as low as reasonably achievable (ALARA). We then discuss certain differences in the way risks from exposure to radionuclides and other carcinogens currently are regulated or assessed which would need to be considered in implementing the proposed regulatory framework for all carcinogens

  4. 78 FR 69101 - Agency Information Collection Activities: Declaration of the Ultimate Consignee That Articles...

    Science.gov (United States)

    2013-11-18

    ... Activities: Declaration of the Ultimate Consignee That Articles Were Exported for Temporary Scientific or... the Declaration of the Ultimate Consignee that Articles were Exported for Temporary Scientific or...: Title: Declaration of the Ultimate Consignee that Articles were Exported for Temporary Scientific or...

  5. Secondary metabolites from Eremostachys laciniata

    DEFF Research Database (Denmark)

    Calis, Ihsan; Güvenc, Aysegül; Armagan, Metin

    2008-01-01

    ), and forsythoside B (18), and five flavone derivatives, luteolin (19), luteolin 7-O-β-D-glucopyranoside (20), luteolin 7-O-(6''-O-β-D-apiofuranosyl)-β-D-glucopyranoside (21), apigenin 7-O-β-D-glucopyranoside (22), and apigenin 7-O-(6''-O-p-coumaroyl)-β-D-glucopyranoside (23). The structures of the metabolites were...... elucidated from spectroscopic (UV, IR, 1D- and 2D-NMR) and ESI-MS evidence, as well as from their specific optical rotation. The presence of these metabolites of three different classes strongly supports the close relationship of the genera Eremostachys and Phlomis....

  6. Is Senna Laxative Use Associated to Cathartic Colon, Genotoxicity, or Carcinogenicity?

    International Nuclear Information System (INIS)

    Morales, M.A.; Bustamante, S.; Hernandez, D.; Bachiller, I.; Rojas, A.

    2009-01-01

    Due to their natural origin, apparent low oral toxicity, effectiveness, and accessibility without a medical prescription, the anthranoid laxatives are a popular remedy for constipation and are frequently used abusively. Therefore, it is important to characterize its harmful and/or toxic effects. The sennosides, main active metabolites of senna, exhibit a very low toxicity in rats, and its genotoxic activity in bacterial strains as well as mammal cells was classified as weak in those cases where it was shown to be significant. The toxicological and mutagenic status of the crude extract of senna, however, is not as well characterized, and it is necessary to do so since it is frequently, and at the same time incorrectly, believed that the chronic use of anthranoid laxatives is a risk factor for the development of colorectal cancer. The objective of this article was to review the information that arises in various scientific medical databases using key words such as senna, sen, Senna alexandrina, Cassia angustifolia, sennosides, laxative toxicity, mainly S and non-S articles of journals with an editorial committee. Web pages of products or companies that publicize or commercialize this type of laxative were not included. This analysis establishes that (1) there is no convincing evidence that the chronic use of senna has, as a consequence, a structural and/or functional alteration of the enteric nerves or the smooth intestinal muscle, (2) there is no relation between long-term administration of a senna extract and the appearance of gastrointestinal tumors or any other type in rats, (3) senna is not carcinogenic in rats even after a two-year daily dose of up to 300 mg/kg/day, and (4) the current evidence does not show that there is a genotoxic risk for patients who take laxatives containing senna extracts or sennosides.

  7. Is senna laxative use associated to cathartic colon, genotoxicity, or carcinogenicity?

    Science.gov (United States)

    Morales, M A; Hernández, D; Bustamante, S; Bachiller, I; Rojas, A

    2009-01-01

    Due to their natural origin, apparent low oral toxicity, effectiveness, and accessibility without a medical prescription, the anthranoid laxatives are a popular remedy for constipation and are frequently used abusively. Therefore, it is important to characterize its harmful and/or toxic effects. The sennosides, main active metabolites of senna, exhibit a very low toxicity in rats, and its genotoxic activity in bacterial strains as well as mammal cells was classified as weak in those cases where it was shown to be significant. The toxicological and mutagenic status of the crude extract of senna, however, is not as well characterized, and it is necessary to do so since it is frequently, and at the same time incorrectly, believed that the chronic use of anthranoid laxatives is a risk factor for the development of colorectal cancer. The objective of this article was to review the information that arises in various scientific medical databases using key words such as senna, sen, Senna alexandrina, Cassia angustifolia, sennosides, laxative toxicity, mainly ISI and non-ISI articles of journals with an editorial committee. Web pages of products or companies that publicize or commercialize this type of laxative were not included. This analysis establishes that (1) there is no convincing evidence that the chronic use of senna has, as a consequence, a structural and/or functional alteration of the enteric nerves or the smooth intestinal muscle, (2) there is no relation between long-term administration of a senna extract and the appearance of gastrointestinal tumors or any other type in rats, (3) senna is not carcinogenic in rats even after a two-year daily dose of up to 300 mg/kg/day, and (4) the current evidence does not show that there is a genotoxic risk for patients who take laxatives containing senna extracts or sennosides.

  8. Is Senna Laxative Use Associated to Cathartic Colon, Genotoxicity, or Carcinogenicity?

    Directory of Open Access Journals (Sweden)

    M. A. Morales

    2009-01-01

    Full Text Available Due to their natural origin, apparent low oral toxicity, effectiveness, and accessibility without a medical prescription, the anthranoid laxatives are a popular remedy for constipation and are frequently used abusively. Therefore, it is important to characterize its harmful and/or toxic effects. The sennosides, main active metabolites of senna, exhibit a very low toxicity in rats, and its genotoxic activity in bacterial strains as well as mammal cells was classified as weak in those cases where it was shown to be significant. The toxicological and mutagenic status of the crude extract of senna, however, is not as well characterized, and it is necessary to do so since it is frequently, and at the same time incorrectly, believed that the chronic use of anthranoid laxatives is a risk factor for the development of colorectal cancer. The objective of this article was to review the information that arises in various scientific medical databases using key words such as senna, sen, Senna alexandrina, Cassia angustifolia, sennosides, laxative toxicity, mainly ISI and non-ISI articles of journals with an editorial committee. Web pages of products or companies that publicize or commercialize this type of laxative were not included. This analysis establishes that (1 there is no convincing evidence that the chronic use of senna has, as a consequence, a structural and/or functional alteration of the enteric nerves or the smooth intestinal muscle, (2 there is no relation between long-term administration of a senna extract and the appearance of gastrointestinal tumors or any other type in rats, (3 senna is not carcinogenic in rats even after a two-year daily dose of up to 300 mg/kg/day, and (4 the current evidence does not show that there is a genotoxic risk for patients who take laxatives containing senna extracts or sennosides.

  9. Protective effects of coffee against oxidative stress induced by the tobacco carcinogen benzo[α]pyrene.

    Science.gov (United States)

    Kalthoff, Sandra; Landerer, Steffen; Reich, Julia; Strassburg, Christian P

    2017-07-01

    Coffee consumption has been epidemiologically associated with a lower risk for liver cirrhosis and cancer. UDP-glucuronosyltransferases (UGT1A) catalyze the detoxification of reactive metabolites thereby acting as indirect antioxidants. Aim of the study was to examine UGT1A regulation in response to Benzo[α]pyrene (BaP) to elucidate the potentially protective effects of coffee on BaP-induced oxidative stress and toxicity. In cell culture (HepG2, KYSE70 cells) and in htgUGT1A-WT mice, UGT1A transcription was activated by BaP, while it was reduced or absent htgUGT1A-SNP (containing 10 commonly occurring UGT1A-SNPs) mice. siRNA-mediated knockdown identified aryl hydrocarbon receptor (AhR) and nuclear factor erythroid2-related factor-2 (Nrf2) as mediators of BaP-induced UGT1A upregulation. Exposure to coffee led to a reduction of BaP-induced production of reactive oxygen species in vitro and in htgUGT1A-WT and -SNP mice. After UGT1A silencing by UGT1A-specific siRNA in cell culture, the coffee-mediated reduction of ROS production was significantly impaired compared to UGT1A expressing cells. A common UGT1A haplotype, prevalent in 9% (homozygous) of the White population, significantly impairs the expression of UGT1A enzymes in response to the putative tobacco carcinogen BaP and is likely to represent a significant risk factor for reduced detoxification and increased genotoxicity. Coffee was demonstrated to inhibit BaP-induced production of oxidative stress by UGT1A activation, and is therefore an attractive candidate for chemoprotection in risk groups for HCC or other tumors. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. BOOK REVIEW: Seeking Ultimates. An Intuitive Guide to Physics

    Science.gov (United States)

    Brown, Neil

    2000-05-01

    Physics has the reputation of being a difficult and dry subject. Many books have been written in attempts to show that the difficulties are not insurmountable, even for the layman, and to convey some of the fascination it provides for those within it. In Seeking Ultimates Peter Landsberg avoids mathematics, the source of so many difficulties, entirely, and seeks to make physics comprehensible by what he terms intuition. He also emphasizes that there is almost no part of science that is completely understood; there are always areas of incompleteness and uncertainty, capable of providing exciting new results, and examples of this are highlighted throughout the book. After an introduction Landsberg starts with macroscopic phenomena for ease of understanding, though one might question whether the chosen topic of thermodynamics is ever going to be easy. Next he looks at microscopic effects, from atomic structure to the fundamental particles of the standard model and their interactions. There follow chapters on time and entropy, on chaos theory, on quantum mechanics and then cosmology. The final chapters look at physical constants (including the anthropic principle), whether physics has room for a creator God (the conclusion is that this is not the province of science), and some thoughts on science as a human activity. The chosen topics are those which have been important in the late twentieth century and remain important. Each chapter cites an eminent scientist as a `hero', though little is made of this. There are occasional historical notes, set in boxes, and a few short poems to leaven the text. What the book achieves is difficult to assess. Removing mathematics and adding a glossary of technical terms do not necessarily allow non-scientists to enjoy the text, as the publisher's note on the back cover suggests. The concepts can baffle the layman even more than the mathematics, and one of the most difficult of all physical concepts permeates so much of this book

  11. Identification of N-acyl-fumonisin B1 as new cytotoxic metabolites of fumonisin mycotoxins.

    Science.gov (United States)

    Harrer, Henning; Laviad, Elad L; Humpf, Hans Ulrich; Futerman, Anthony H

    2013-03-01

    Fumonisins are mycotoxins produced by Fusarium species. The predominant derivative, fumonisin B1 (FB1), occurs in food and feed and is of health concern due to its hepatotoxic and carcinogenic effects. However, the role of FB1 metabolites on the mechanism of the toxicity, the inhibition of the ceramide synthesis, is unknown. The aim of this study was to identify new fumonisin metabolites and to evaluate their cytotoxic potential. MS, molecular biology, and in vitro enzyme assays were used to investigate fumonisin metabolism in mammalian cells overexpressing human ceramide synthase (CerS) genes. N-acyl-FB1 derivatives were detected as new metabolites in cultured cells at levels of up to 10 pmol/mg of protein. The N-acylation of FB1 and hydrolyzed FB1 was analyzed in several cell lines, including cells overexpressing CerS. The acyl-chain length of the N-acyl fumonisins depends on the CerS isoform acylating them. The N-acyl fumonisins are more cytotoxic than the parent fumonisin B1. The identification of N-acyl fumonisins with various acyl chain lengths together with the observed cytotoxicity of these compounds is a new aspect of fumonisin-related toxicity. Therefore, these new metabolites might play an important role in the mode of action of fumonisins. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Synthesis and characterization of N-demethylated metabolites of malachite green and leucomalachite green.

    Science.gov (United States)

    Cho, Bongsup P; Yang, Tianle; Blankenship, Lonnie R; Moody, Joanna D; Churchwell, Mona; Beland, Frederick A; Culp, Sandra J

    2003-03-01

    Malachite green (MG), a triphenylmethane dye used to treat fungal and protozoan infections in fish, undergoes sequential oxidation to produce various N-demethylated derivatives (monodes-, dides(sym)-, dides(unsym)-, trides-, and tetrades-) both before and after reduction to leucomalachite green (LMG). The close structure resemblance of the metabolites with aromatic amine carcinogens implicates a potential genotoxicity from exposure to MG. The availability of the synthetic standards is important for metabolic and DNA adduct studies of MG. This paper describes a simple and versatile method for the synthesis of MG, LMG, and their N-demethylated metabolites. The synthesis involves a coupling of 4-(dimethylamino)benzophenone or 4-nitrobenzophenone with the aryllithium reagents derived from appropriately substituted 4-bromoaniline derivatives, followed by treatment with HCl in methanol. The resulting cationic MG and their leuco analogues showed systematic UV/vis spectral and tandem mass fragmentation patterns consistent with sequential N-demethylation. The extensive (1)H and (13)C spectral assignments of the metabolites were aided by the availability of (13)C(7)-labeled MG and LMG. The results indicate the existence of a resonance structure with the cationic charge located in the central methane carbon (C(7)). The synthetic procedure is general in scope so that it can be extended to the preparation of N-demethylated metabolites of other structurally related N-methylated triphenylmethane dyes.

  13. The carcinogenic air pollutant 3-nitrobenzanthrone induces GC to TA transversion mutations in human p53 sequences.

    Science.gov (United States)

    vom Brocke, Jochen; Krais, Annette; Whibley, Catherine; Hollstein, Monica C; Schmeiser, Heinz H

    2009-01-01

    3-Nitrobenzanthrone (3-NBA) is a potent mutagen and a suspected human carcinogen present in particulate matter of diesel exhaust and ambient air pollution. Employing an assay with human p53 knock-in (Hupki) murine embryonic fibroblasts (HUFs), we examined p53 mutations induced by 3-NBA and its active metabolite, N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA). Twenty-nine immortalized cultures (cell lines) from 89 HUF primary cultures exposed at passage 1 for 5 days to 2 microM 3-NBA harboured 22 different mutations in the human DNA-binding domain sequence of the Hupki p53 tumour suppressor gene. The most frequently observed mutation was GC to TA transversion (46%), corroborating previous mutation studies with 3-NBA, and consistent with the presence of persistent 3-NBA-guanosine adducts found in DNA of exposed rodents. Six of the transversions found solely in 3-NBA-treated HUFs have not been detected thus far in untreated HUFs, but have been found repeatedly in human lung tumours. (32)P-post-labelling adduct analysis of DNA from HUF cells treated with 2 microM 3-NBA for 5 days showed a pattern similar to that found in vivo, indicating the metabolic competence of HUF cells to metabolize 3-NBA to electrophilic intermediates. Total DNA binding was 160 +/- 56 per 10(7) normal nucleotides with N(2)-guanosine being the major adduct. In contrast, identical treatment with N-OH-3-ABA resulted in a 100-fold lower level of specific DNA adducts and no carcinogen-specific mutation pattern in the Hupki assay. This indicates that the level of DNA adduct formation by the mutagen is critical to obtain specific mutation spectra in the assay. Our results are consistent with previous experiments in Muta Mouse and are compatible with the possibility that diesel exhaust exposure contributes to mutation load in humans and to lung cancer risk.

  14. Primary expectations of secondary metabolites

    Science.gov (United States)

    My program examines the plant secondary metabolites (i.e. phenolics) important for human health, and which impart the organoleptic properties that are quality indicators for fresh and processed foods. Consumer expectations such as appearance, taste, or texture influence their purchasing decisions; a...

  15. Disruption of spindle checkpoint function in rats following 28 days of repeated administration of renal carcinogens.

    Science.gov (United States)

    Kimura, Masayuki; Mizukami, Sayaka; Watanabe, Yousuke; Hasegawa-Baba, Yasuko; Onda, Nobuhiko; Yoshida, Toshinori; Shibutani, Makoto

    2016-02-01

    We previously reported that 28-day exposure to hepatocarcinogens that facilitate cell proliferation specifically alters the expression of G1/S checkpoint-related genes and proteins, induces aberrant early expression of ubiquitin D (UBD) at the G2 phase, and increases apoptosis in the rat liver, indicating G1/S and spindle checkpoint dysfunction. The present study aimed to determine the time of onset of carcinogen-specific cell-cycle disruption after repeated administration of renal carcinogens for up to 28 days. Rats were orally administered the renal carcinogens nitrofurantoin (NFT), 1-amino-2,4-dibromoantraquinone (ADAQ), and 1,2,3-trichloropropane (TCP) or the non-carcinogenic renal toxicants 1-chloro-2-propanol, triamterene, and carboxin for 3, 7 or 28 days. Both immunohistochemical single-molecule analysis and real-time RT-PCR analysis revealed that carcinogen-specific expression changes were not observed after 28 days of administration. However, the renal carcinogens ADAQ and TCP specifically reduced the number of cells expressing phosphorylated-histone H3 at Ser10 in both UBD(+) cells and proliferating cells, suggestive of insufficient UBD expression at the M phase and early transition of proliferating cells from the M phase, without increasing apoptosis, after 28 days of administration. In contrast, NFT, which has marginal carcinogenic potential, did not induce such cellular responses. These results suggest that it may take 28 days to induce spindle checkpoint dysfunction by renal carcinogens; however, induction of apoptosis may not be essential. Thus, induction of spindle checkpoint dysfunction may be dependent on carcinogenic potential of carcinogen examined, and marginal carcinogens may not exert sufficient responses even after 28 days of administration.

  16. The effects of environmental chemical carcinogens on the microRNA machinery.

    Science.gov (United States)

    Izzotti, A; Pulliero, A

    2014-07-01

    The first evidence that microRNA expression is early altered by exposure to environmental chemical carcinogens in still healthy organisms was obtained for cigarette smoke. To date, the cumulative experimental data indicate that similar effects are caused by a variety of environmental carcinogens, including polycyclic aromatic hydrocarbons, nitropyrenes, endocrine disruptors, airborne mixtures, carcinogens in food and water, and carcinogenic drugs. Accordingly, the alteration of miRNA expression is a general mechanism that plays an important pathogenic role in linking exposure to environmental toxic agents with their pathological consequences, mainly including cancer development. This review summarizes the existing experimental evidence concerning the effects of chemical carcinogens on the microRNA machinery. For each carcinogen, the specific microRNA alteration signature, as detected in experimental studies, is reported. These data are useful for applying microRNA alterations as early biomarkers of biological effects in healthy organisms exposed to environmental carcinogens. However, microRNA alteration results in carcinogenesis only if accompanied by other molecular damages. As an example, microRNAs altered by chemical carcinogens often inhibits the expression of mutated oncogenes. The long-term exposure to chemical carcinogens causes irreversible suppression of microRNA expression thus allowing the transduction into proteins of mutated oncogenes. This review also analyzes the existing knowledge regarding the mechanisms by which environmental carcinogens alter microRNA expression. The underlying molecular mechanism involves p53-microRNA interconnection, microRNA adduct formation, and alterations of Dicer function. On the whole, reported findings provide evidence that microRNA analysis is a molecular toxicology tool that can elucidate the pathogenic mechanisms activated by environmental carcinogens. Copyright © 2014 Elsevier GmbH. All rights reserved.

  17. Abundant Rodent Furan-Derived Urinary Metabolites Are Associated with Tobacco Smoke Exposure in Humans.

    Science.gov (United States)

    Grill, Alex E; Schmitt, Thaddeus; Gates, Leah A; Lu, Ding; Bandyopadhyay, Dipankar; Yuan, Jian-Min; Murphy, Sharon E; Peterson, Lisa A

    2015-07-20

    Furan, a possible human carcinogen, is found in heat treated foods and tobacco smoke. Previous studies have shown that humans are capable of converting furan to its reactive metabolite, cis-2-butene-1,4-dial (BDA), and therefore may be susceptible to furan toxicity. Human risk assessment of furan exposure has been stymied because of the lack of mechanism-based exposure biomarkers. Therefore, a sensitive LC-MS/MS assay for six furan metabolites was applied to measure their levels in urine from furan-exposed rodents as well as in human urine from smokers and nonsmokers. The metabolites that result from direct reaction of BDA with lysine (BDA-N(α)-acetyllysine) and from cysteine-BDA-lysine cross-links (N-acetylcysteine-BDA-lysine, N-acetylcysteine-BDA-N(α)-acetyllysine, and their sulfoxides) were targeted in this study. Five of the six metabolites were identified in urine from rodents treated with furan by gavage. BDA-N(α)-acetyllysine, N-acetylcysteine-BDA-lysine, and its sulfoxide were detected in most human urine samples from three different groups. The levels of N-acetylcysteine-BDA-lysine sulfoxide were more than 10 times higher than that of the corresponding sulfide in many samples. The amount of this metabolite was higher in smokers relative to that in nonsmokers and was significantly reduced following smoking cessation. Our results indicate a strong relationship between BDA-derived metabolites and smoking. Future studies will determine if levels of these biomarkers are associated with adverse health effects in humans.

  18. Molecular basis of carcinogenicity of tungsten alloy particles

    Energy Technology Data Exchange (ETDEWEB)

    Harris, Robert M.; Williams, Tim D.; Waring, Rosemary H.; Hodges, Nikolas J., E-mail: n.hodges@bham.ac.uk

    2015-03-15

    The tungsten alloy of 91% tungsten, 6% nickel and 3% cobalt (WNC 91–6–3) induces rhabdomyosarcoma when implanted into a rat thigh muscle. To investigate whether this effect is species-specific human HSkMc primary muscle cells were exposed to WNC 91–6–3 particles and responses were compared with those from a rat skeletal muscle cell line (L6-C11). Toxicity was assessed by the adenylate kinase assay and microscopy, DNA damage by the Comet assay. Caspase 3 enzyme activity was measured and oligonucleotide microarrays were used for transcriptional profiling. WNC 91–6–3 particles caused toxicity in cells adjacent to the particles and also increased DNA strand breaks. Inhibition of caspase 3 by WNC 91–6–3 occurred in rat but not in human cells. In both rat and human cells, the transcriptional response to WNC 91–6–3 showed repression of transcripts encoding muscle-specific proteins with induction of glycolysis, hypoxia, stress responses and transcripts associated with DNA damage and cell death. In human cells, genes encoding metallothioneins were also induced, together with genes related to angiogenesis, dysregulation of apoptosis and proliferation consistent with pre-neoplastic changes. An alloy containing iron, WNF 97–2–1, which is non-carcinogenic in vivo in rats, did not show these transcriptional changes in vitro in either species while the corresponding cobalt-containing alloy, WNC 97–2–1 elicited similar responses to WNC 91–6–3. Tungsten alloys containing both nickel and cobalt therefore have the potential to be carcinogenic in man and in vitro assays coupled with transcriptomics can be used to identify alloys, which may lead to tumour formation, by dysregulation of biochemical processes. - Highlights: • Use of transcriptomics to identify likely carcinogenic tungsten alloys in vitro • Cobalt containing alloys cause oxidative stress, DNA-damage and perturb apoptosis. • Presence of cobalt causes changes in gene expression

  19. Molecular biomarkers of oxidative stress associated with bromate carcinogenicity

    International Nuclear Information System (INIS)

    Delker, Don; Hatch, Gary; Allen, James; Crissman, Bobby; George, Michael; Geter, David; Kilburn, Steve; Moore, Tanya; Nelson, Gail; Roop, Barbara; Slade, Ralph; Swank, Adam; Ward, William; DeAngelo, Anthony

    2006-01-01

    Potassium bromate (KBrO 3 ) is a chemical oxidizing agent found in drinking water as a disinfection byproduct of surface water ozonation. Chronic exposures to KBrO 3 cause renal cell tumors in rats, hamsters and mice and thyroid and testicular mesothelial tumors in rats. Experimental evidence indicates that bromate mediates toxicological effects via the induction of oxidative stress. To investigate the contribution of oxidative stress in KBrO 3 -induced cancer, male F344 rats were administered KBrO 3 in their drinking water at multiple concentrations for 2-100 weeks. Gene expression analyses were performed on kidney, thyroid and mesothelial cell RNA. Families of mRNA transcripts differentially expressed with respect to bromate treatment included multiple cancer, cell death, ion transport and oxidative stress genes. Multiple glutathione metabolism genes were up-regulated in kidney following carcinogenic (400 mg/L) but not non-carcinogenic (20 mg/L) bromate exposures. 8-Oxodeoxyguanosine glycosylase (Ogg1) mRNA was up-regulated in response to bromate treatment in kidney but not thyroid. A dramatic decrease in global gene expression changes was observed following 1 mg/L compared to 20 mg/L bromate exposures. In a separate study oxygen-18 ( 18 O) labeled KBrO 3 was administered to male rats by oral gavage and tissues were analyzed for 18 O deposition. Tissue enrichment of 18 O was observed at 5 and 24 h post-KBr 18 O 3 exposure with the highest enrichment occurring in the liver followed by the kidney, thyroid and testes. The kidney dose response observed was biphasic showing similar statistical increases in 18 O deposition between 0.25 and 50 mg/L (equivalent dose) KBr 18 O 3 followed by a much greater increase above 50 mg/L. These results suggest that carcinogenic doses of potassium bromate require attainment of a threshold at which oxidation of tissues occurs and that gene expression profiles may be predictive of these physiological changes in renal homeostasis

  20. Analysis of renal cell transformation following exposure to trichloroethene in vivo and its metabolite S-(dichlorovinyl)-L-cysteine in vitro

    International Nuclear Information System (INIS)

    Mally, Angela; Walker, Cheryl L.; Everitt, Jeffrey I.; Dekant, Wolfgang; Vamvakas, Spiros

    2006-01-01

    Trichloroethene (TCE) is classified as a potential human carcinogen although there is a significant debate regarding the mechanism of TCE induced renal tumor formation. This controversy stems in part from the extremely high doses of TCE required to induce renal tumors and the potential contribution of the associated nephrotoxicity to tumorigenesis. We have used Eker rats, which are uniquely susceptible to renal carcinogens, to determine if exposures to TCE in vivo or exposure to its metabolite S-(dichlorovinyl)-L-cysteine (DCVC) in vitro can transform kidney epithelial cells in the absence of cytotoxicity. Treatment with TCE (0, 100, 250, 500, 1000 mg/kg bw by gavage, 5 days a week) for 13 weeks resulted in a significant increase in cell proliferation in kidney tubule cells, but did not enhance formation of preneoplastic lesions or tumor incidence in Eker rat kidneys as compared to controls. In vitro, concentrations of DCVC, which reduced cell survival to 50%, were able to transform rat kidney epithelial cells. However, no carcinogen-specific mutations were identified in the VHL or Tsc-2 tumor suppressor genes in the transformants. Taken together, the inability of TCE to enhance formation of preneoplastic changes or neoplasia and the absence of carcinogen-specific alteration of genes accepted to be critical for renal tumor development suggest that TCE mediated carcinogenicity may occur secondary to continuous toxic injury and sustained regenerative cell proliferation

  1. Marine metabolites: The sterols of soft coral

    Digital Repository Service at National Institute of Oceanography (India)

    Sarma, N.S.; Krishna, M.S.; Pasha, Sk.G.; Rao, T.S.P.; Venkateswarlu, Y.; Parameswaran, P.S.

    Sterols constitute a major group of secondary metabolites of soft corals. Several of these compounds have the 'usual' 3 beta-hydroxy, delta sup(5) (or delta sup(0)) cholestane skeleton, a large number of these metabolites are polar sterols...

  2. Familial Resemblance for Serum Metabolite Concentrations

    NARCIS (Netherlands)

    Draisma, H.H.M.; Beekman, M.; Pool, R.; van Ommen, G.J.B; Vaarhorst, A.A.M.; de Craen, A.J.; Willemsen, G.; Slagboom, P.E.; Boomsma, D.I.

    2013-01-01

    Metabolomics is the comprehensive study of metabolites, which are the substrates, intermediate, and end products of cellular metabolism. The heritability of the concentrations of circulating metabolites bears relevance for evaluating their suitability as biomarkers for disease. We report aspects of

  3. Retraction: Evaluation of carcinogenic effects of electromagnetic fields (EMF).

    Science.gov (United States)

    Mehic, Bakir

    2010-11-01

    The Editor-in-chief of the Bosnian Journal of Basic Medical Sciences has decided to retract the article from Bayazit V et al. [1] entitled as: "Evaluation of carcinogenic effects of electromagnetic fields (EMF)" published in Bosn J Basic Med Sci. 2010 Aug;10(3):245-50. After the editorial office was alerted of possible plagiarism in the article, it conducted thorough investigation and concluded that the article apparently represents plagiarized material from two World Health Organization reports, one European Commission report and other sources. Since this is considered scientific plagiarism and scientific misconduct, Editor-in-chief has decided to withdraw the article. The authors have agreed with the editorial office decision.

  4. Chemistry of mutagens and carcinogens in broiled food.

    Science.gov (United States)

    Nishimura, S

    1986-01-01

    From a chemical point of view, the following subjects are important areas in studies on mutagens and carcinogens in broiled foods. In addition to heterocyclic amines which need microsomal activation, the structural elucidation of more labile direct-acting mutagens is necessary. It is known that there are still various unknown minor mutagens in broiled foods. Although the structural characterization of such compounds is more difficult, it is important since they might be hazardous in spite of their low mutagenicity. A more feasible and easier method for quantitative analysis of mutagens, in addition to HPLC and GC/MS methods presently employed, must be developed. The mechanism of formation of mutagens by broiling of food should be studied. An effective chemical method to prevent formation of mutagens or to destroy them, once formed, should be developed. PMID:3757944

  5. IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans

    Science.gov (United States)

    Blair, Aaron; Vineis, Paolo; Ahrens, Wolfgang; Andersen, Aage; Anto, Josep M.; Armstrong, Bruce K.; Baccarelli, Andrea A.; Beland, Frederick A.; Berrington, Amy; Bertazzi, Pier Alberto; Birnbaum, Linda S.; Brownson, Ross C.; Bucher, John R.; Cantor, Kenneth P.; Cardis, Elisabeth; Cherrie, John W.; Christiani, David C.; Cocco, Pierluigi; Coggon, David; Comba, Pietro; Demers, Paul A.; Dement, John M.; Douwes, Jeroen; Eisen, Ellen A.; Engel, Lawrence S.; Fenske, Richard A.; Fleming, Lora E.; Fletcher, Tony; Fontham, Elizabeth; Forastiere, Francesco; Frentzel-Beyme, Rainer; Fritschi, Lin; Gerin, Michel; Goldberg, Marcel; Grandjean, Philippe; Grimsrud, Tom K.; Gustavsson, Per; Haines, Andy; Hartge, Patricia; Hansen, Johnni; Hauptmann, Michael; Heederik, Dick; Hemminki, Kari; Hemon, Denis; Hertz-Picciotto, Irva; Hoppin, Jane A.; Huff, James; Jarvholm, Bengt; Kang, Daehee; Karagas, Margaret R.; Kjaerheim, Kristina; Kjuus, Helge; Kogevinas, Manolis; Kriebel, David; Kristensen, Petter; Kromhout, Hans; Laden, Francine; Lebailly, Pierre; LeMasters, Grace; Lubin, Jay H.; Lynch, Charles F.; Lynge, Elsebeth; ‘t Mannetje, Andrea; McMichael, Anthony J.; McLaughlin, John R.; Marrett, Loraine; Martuzzi, Marco; Merchant, James A.; Merler, Enzo; Merletti, Franco; Miller, Anthony; Mirer, Franklin E.; Monson, Richard; Nordby, Karl-Cristian; Olshan, Andrew F.; Parent, Marie-Elise; Perera, Frederica P.; Perry, Melissa J.; Pesatori, Angela Cecilia; Pirastu, Roberta; Porta, Miquel; Pukkala, Eero; Rice, Carol; Richardson, David B.; Ritter, Leonard; Ritz, Beate; Ronckers, Cecile M.; Rushton, Lesley; Rusiecki, Jennifer A.; Rusyn, Ivan; Samet, Jonathan M.; Sandler, Dale P.; de Sanjose, Silvia; Schernhammer, Eva; Costantini, Adele Seniori; Seixas, Noah; Shy, Carl; Siemiatycki, Jack; Silverman, Debra T.; Simonato, Lorenzo; Smith, Allan H.; Smith, Martyn T.; Spinelli, John J.; Spitz, Margaret R.; Stallones, Lorann; Stayner, Leslie T.; Steenland, Kyle; Stenzel, Mark; Stewart, Bernard W.; Stewart, Patricia A.; Symanski, Elaine; Terracini, Benedetto; Tolbert, Paige E.; Vainio, Harri; Vena, John; Vermeulen, Roel; Victora, Cesar G.; Ward, Elizabeth M.; Weinberg, Clarice R.; Weisenburger, Dennis; Wesseling, Catharina; Weiderpass, Elisabete; Zahm, Shelia Hoar

    2015-01-01

    Background: Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans. Objectives: The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process to determine the validity of these concerns. Here, we present the results of that examination, review the history of IARC evaluations, and describe how the IARC evaluations are performed. Discussion: We concluded that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various disciplines and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed. Conclusions: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public’s health. Citation: Pearce N, Blair A, Vineis P, Ahrens W, Andersen A, Anto JM, Armstrong BK, Baccarelli AA, Beland FA, Berrington A, Bertazzi PA, Birnbaum LS, Brownson RC, Bucher JR, Cantor KP

  6. The assessment of the carcinogenic effects of low dose radiation

    International Nuclear Information System (INIS)

    Tubiana, M.; Lafuma, J.; Masse, R.; Latarjet, R.

    1991-01-01

    It is concluded that the exclusion of patients for the purposes of risk estimation, the choice of a particular relative risk projection model and of a dose reduction factor equal to 2 are all decisions which result in an overestimation of the actual risk. These choices can be understood when the aim is radiation protection and when it is safer to overestimate the risk; however, they are open to criticism if the aim is a realistic assessment of the risk. For low doses, below 50 mSv/year, and when all causes of uncertainty are added, the actual risk might be markedly lower than the risk estimated with the ICRP (1991) carcinogenic risk coefficient and the DRF estimated by ICRP. Future studies should aim at providing direct and more precise assessments of risk coefficients in the low dose region. (Author)

  7. [Comparative carcinogenic properties of basalt fiber and chrysotile-asbestos].

    Science.gov (United States)

    Nikitina, O V; Kogan, F M; Vanchugova, N N; Frash, V N

    1989-01-01

    In order to eliminate asbestos adverse effect on workers' health it was necessary to use mineral rayon, primarily basalt fibre, instead of asbestos. During a chronic experiment on animals the oncogenicity of 2 kinds of basalt fibre was studied compared to chrysotile asbestos. The dust dose of 25 mg was twice administered by intraperitonial route. All types of dust induced the onset of intraperitonial mesotheliomas but neoplasm rates were significantly lower in the groups exposed to basalt fibre. There was no credible data on the differences between the groups exposed to various types of basalt fibre. Since the latter produced some oncogenic effect, it was necessary to develop a complex of antidust measures, fully corresponding to the measures adopted for carcinogenic dusts.

  8. Nuclear DNA synthesis rate and labelling index: effects of carcinogenic and non-carcinogenic chemicals on its behaviour in the organism of growing CBA mice

    International Nuclear Information System (INIS)

    Amlacher, E.; Rudolph, C.

    1978-01-01

    Well known bioassays have been compared with the author's thymidine incorporation-screening system and other assays based on biochemical quantification of DNA synthesis as a possibility of identification of carcinogens. The partial inhibition of the whole DNA synthesis in a proliferating cell population after treatment with toxic and carcinogenic chemicals is an early common response especially in hepatectomized animal, livers caused by the effects of those substances. However, by quantitative evaluation of the nuclear DNA synthesis rate as a basic parameter, using autoradiographs of kidney and liver of juvenile growing CBA mice, it is possible to differentiate carcinogenic from non-carcinogenic chemicals by means of silver grain counting after 3 H-TdR incorporation. On the contrary, the whole DNA synthesis, expressed by the 3 H-labelling index (in per cent) of kidney and liver, did not permit such a differentiation in the experimental arrangement used. It could be demonstrated that carcinogenic compounds of different chemical classes partially inhibit the nuclear DNA synthesis rate significantly over a period of more than 24 hours. The tested non-carcinogenic compounds did not show this suppressive effect on the nuclear DNA synthesis rate. (author)

  9. DNA-adducts in fish exposed to alkylating carcinogens

    International Nuclear Information System (INIS)

    Giam, C.S.; Holliday, T.L.; Williams, J.L.; Bahnson, A.; Weller, R.; Hinton, D.E.

    1988-01-01

    There are limited studies on DNA-adduct formation following exposure of fish or fish cells to carcinogens. It will be essential to determine if procarcinogens and carcinogens form the same DNA-adducts in different liver cells and how these compare to those reported in mammalian livers. They are also interested in the influence of different alkylating agents on the type and quantity of DNA-adduct formation and repair in fish. While eggs or small fish are ideal for routine screening, large fish such as trout (Salmo gairdneri) is needed initially for the development of analytical procedures for the isolation, quantitation and identification of various adducts. Trout (Salmo gairdneri) weighing approximately 250 grams were acclimatized at 13 degree C before being given i.p. injection of diethylnitrosoamine (DEN). The exposure period varied, though most animals were sacrificed after 24 hours. Their livers were excised and DNA was isolated mainly according the procedure of Croy et al. The neutral thermal hydrolysate and the acid hydrolysate were analyzed by HPLC-Fluorescent detector for 7-ethylguanine and O 6 -ethylguanine, respectively. O 6 -ethylguanine was detected, 7-ethylguanine was not detected. Attempts are being made to improve the detection of the latter compound. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) was used to establish nanogram quantities of the ethylated bases. Laser desorption FT-IC-MS is particularly useful for characterizing thermally-labile and involatile nucleosides or nucleotides. Excretion of DEN was rapid and high. Exposure of trout (and other fish) to various ethylating agents will be discussed

  10. Changing the field of carcinogenicity testing of human pharmaceuticals by emphasizing mode of action

    NARCIS (Netherlands)

    Laan, J.W. van der; Duijndam, B.; Hoorn, T. van den; Woutersen, R.; Water, B. van de

    2017-01-01

    Lifetime testing for carcinogenicity of pharmaceuticals in rodents has been a controversial issue since the start of the International Conference on Harmonisation in 1990. Since 2010 the debate reached a new level following the proposal that a negative outcome of carcinogenicity studies can be

  11. OVERVIEW OF DRINKING WATER MUTAGENICITY AND CARCINOGENICITY AND RISK FOR BLADDER CANCER

    Science.gov (United States)

    Among the 11 disinfection by-products (DBPs) in drinking water that are regulated by the U.S. EPA, (a) 2 DBPs (chloroacetic acid and chlorite) are not carcinogenic-in either of 2 species; (b) chlorite is not carcinogenic in 3 rodent assays and has never been tested for genotoxici...

  12. Impact of occupational carcinogens on lung cancer risk in a general population

    NARCIS (Netherlands)

    De Matteis, S.; Consonni, D.; Lubin, J.H.; Tucker, M.; Peters, S.; Vermeulen, R.; Kromhout, H.; Bertazzi, P.A.; Caporaso, N.E.; Pesatori, A.C.; Wacholder, S.; Landi, M.T.

    2012-01-01

    BACKGROUND: Exposure to occupational carcinogens is an important preventable cause of lung cancer. Most of the previous studies were in highly exposed industrial cohorts. Our aim was to quantify lung cancer burden attributable to occupational carcinogens in a general population. METHODS: We applied

  13. Inter-laboratory comparison of turkey in ovo carcinogenicity assessment (IOCA) of hepatocarcinogens.

    Science.gov (United States)

    Enzmann, H; Brunnemann, K; Iatropoulos, M; Shpyleva, S; Lukyanova, N; Todor, I; Moore, M; Spicher, K; Chekhun, V; Tsuda, H; Williams, G

    2013-09-01

    In three independent laboratories carcinogens (diethylnitrosamine, DEN, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone, NNK) and non-carcinogens (N-nitrosoproline, nicotine) were evaluated in turkey eggs for in ovo carcinogenicity assessment (IOCA). Compounds were injected into aseptic fertilized eggs. After incubation for 24 days, foci of altered hepatocytes (FAH), some with a pseudoglandular structure and/or signs of compression of the surrounding tissue were observed in the fetal liver. All laboratories were able to distinguish unequivocally the hepatocarcinogen-exposed groups from those exposed to non-carcinogens or the vehicle controls, based on the pre-specified evaluation parameters: tumor-like lesions, pseudoglandular areas and FAH. In addition to focal changes, only the carcinogens induced hepatocellular karyomegaly. Lower doses of the carcinogens, which did not induce FAH, were sufficient to induce hepatocellular karyomegaly. After exposure to 4 mg DEN, gall bladder agenesis was observed in all fetuses. The IOCA may be a valuable tool for early investigative studies on carcinogenicity and since it does not use rodents may complement chronic rat or mouse bioassays. Test substances that are positive in both rodents and fertilized turkey eggs are most probably trans-species carcinogens with particular significance for humans. The good concordance observed among the three laboratories demonstrates that the IOCA is a reliable and robust method. Copyright © 2012 Elsevier GmbH. All rights reserved.

  14. 78 FR 16681 - International Conference on Harmonisation; Proposed Change to Rodent Carcinogenicity Testing of...

    Science.gov (United States)

    2013-03-18

    ...-evidence (WOE) factors proposed for inclusion in CADs. II. Past Experience With Carcinogenicity Assessment... Medicines Agency; and the Japanese Ministry of Health, Labour and Welfare. We would request that CADs be... WOE factors proposed for inclusion in carcinogenicity assessment documents. Submit either electronic...

  15. Identification of a new reactive metabolite of pyrrolizidine alkaloid retrorsine: (3H-pyrrolizin-7-yl)methanol.

    Science.gov (United States)

    Fashe, Muluneh M; Juvonen, Risto O; Petsalo, Aleksanteri; Rahnasto-Rilla, Minna; Auriola, Seppo; Soininen, Pasi; Vepsäläinen, Jouko; Pasanen, Markku

    2014-11-17

    Pyrrolizidine alkaloids (PAs) such as retrorsine are common food contaminants that are known to be bioactivated by cytochrome P450 enzymes to putative hepatotoxic, genotoxic, and carcinogenic metabolites known as dehydropyrrolizidine alkaloids (DHPs). We compared how both electrochemical (EC) and human liver microsomal (HLM) oxidation of retrorsine could produce short-lived intermediate metabolites; we also characterized a toxicologically important metabolite, (3H-pyrrolizin-7-yl)methanol. The EC cell was coupled online or offline to a liquid chromatograph/mass spectrometer (LC/MS), whereas the HLM oxidation was performed in 100 mM potassium phosphate (pH 7.4) in the presence of NADPH at 37 °C. The EC cell oxidation of retrorsine produced 12 metabolites, including dehydroretrorsine (m/z 350, [M + H(+)]), which was degraded to a new reactive metabolite at m/z 136 ([M + H(+)]). The molecular structure of this small metabolite was determined using high-resolution mass spectrometry and NMR spectroscopy followed by chemical synthesis. In addition, we also identified another minor but reactive metabolite at m/z 136, an isomer of (3H-pyrrolizin-7-yl)methanol. Both (3H-pyrrolizin-7-yl)methanol and its minor isomer were also observed after HLM oxidation of retrorsine and other hepatotoxic PAs such as lasiocarpine and senkirkin. In the presence of reduced glutathione (GSH), each isomer formed identical GSH conjugates at m/z 441 and m/z 730 in the negative ESI-MS. Because (3H-pyrrolizine-7-yl)methanol) and its minor isomer subsequently reacted with GSH, it is concluded that (3H-pyrrolizin-7-yl)methanol may be a common toxic metabolite arising from PAs.

  16. Moesin Is a Biomarker for the Assessment of Genotoxic Carcinogens in Mouse Lymphoma

    Science.gov (United States)

    Lee, Yoen Jung; Choi, In-Kwon; Sheen, Yhun Yhong; Park, Sue Nie; Kwon, Ho Jeong

    2012-01-01

    1,2-Dibromoethane and glycidol are well known genotoxic carcinogens, which have been widely used in industry. To identify a specific biomarker for these carcinogens in cells, the cellular proteome of L5178Y mouse lymphoma cells treated with these compounds was analyzed by 2-dimensional gel electrophoresis (2-DE) and MALDI-TOF mass spectrometry (MS). Of 50 protein spots showing a greater than 1.5-fold increase or decrease in intensity compared to control cells on a 2-D gel, we focused on the candidate biomarker moesin. Western analysis using monoclonal rabbit anti-moesin confirmed the identity of the protein and its increased level of expression upon exposure to the carcinogenic compounds. Moesin expression also increased in cells treated with six additional genotoxic carcinogens, verifying that moesin could serve as a biomarker to monitor phenotypic change upon exposure to genotoxic carcinogens in L5178Y mouse lymphoma cells. PMID:22358511

  17. The in vivo rodent test systems for assessment of carcinogenic potential

    DEFF Research Database (Denmark)

    van der Laan, Jan-Willem; Spindler, Per

    2002-01-01

    A Drug Information Association (DIA) workshop was held in May 2001 to discuss the outcome of the International Life Sciences Institute-Health and Environmental Sciences Institute (ILSI-HESI) project on alternative models for carcinogenicity assessment such as the P53(+/-) and XPA(+/-) knockout...... mouse models, the RasH2 and Tg.AC transgenic mouse models, and the neonatal mouse model. The "ICH Guideline S1B on Testing for Carcinogenicity of Pharmaceuticals" advocates that carcinogenicity testing of pharmaceuticals, when needed, might be carried out choosing one 2-year rodent carcinogenicity study...... (rat) plus one other study that supplements the 2-year study and providing additional information that is not readily available from the 2-year study: either (1) a short- or medium-term in vivo rodent test system or (2) a 2-year carcinogenicity study in a second rodent species (mouse). Another topic...

  18. PCB 28 metabolites elimination kinetics in human plasma on a real case scenario: Study of hydroxylated polychlorinated biphenyl (OH-PCB) metabolites of PCB 28 in a highly exposed German Cohort.

    Science.gov (United States)

    Quinete, Natalia; Esser, André; Kraus, Thomas; Schettgen, Thomas

    2017-07-05

    Polychlorinated biphenyls (PCBs) are suspected of carcinogenic, neurotoxic and immunotoxic effects in animals and humans. Although background levels of PCBs have been slowly decreased after their ban, they are still among the most persistent and ubiquitous pollutants in the environment, remaining the subject of great concern. PCB 28 is a trichlorinated PCB found in high concentrations not only in human plasma but also in indoor air in Europe, yet little is known about its metabolic pathway and potential metabolites in humans. The present study aims to elucidate the kinetics of metabolite formation and elimination by analyzing four hydroxylated PCBs (OH-PCBs) in human plasma as potential metabolites of the PCB 28 congener. For this purpose, the study was conducted in plasma samples of highly PCB-exposed individuals (N=268), collected from 2010 to 2014 as a representation of a real case scenario with longitudinal data. OH-PCBs have been predicted, synthesized in the course of this study and further identified and quantitated in human plasma. This is the first time that previously unknown PCB 28 metabolites have been measured in human plasma and half-lives have been estimated for PCB metabolites, which could then provide further understanding in the toxicological consequences of exposure to PCBs in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Activation and detoxification metabolism of urban air pollutants 2-nitrobenzanthrone and carcinogenic 3-nitrobenzanthrone by rat and mouse hepatic microsomes.

    Science.gov (United States)

    Stiborova, Marie; Cechova, Tereza; Borek-Dohalska, Lucie; Moserova, Michaela; Frei, Eva; Schmeiser, Heinz H; Paca, Jan; Arlt, Volker M

    2012-01-01

    2-Nitrobenzanthrone (2-NBA) has recently been detected in ambient air particulate matter. Its isomer 3-nitrobenzanthrone (3-NBA) is a potent mutagen and suspected human carcinogen identified in diesel exhaust. Understanding which enzymes are involved in metabolism of these toxicants is important in the assessment of individual susceptibility. Here, metabolism of 2-NBA and 3-NBA by rat and mouse hepatic microsomes containing cytochromes P450 (CYPs), their reductase (NADPH:CYP reductase), and NADH:cytochrome b5 reductase was investigated under anaerobic and aerobic conditions. In addition, using the same microsomal systems, 2-NBA and 3-NBA were evaluated to be enzymatically activated under anaerobic conditions to species generating 2-NBA- and 3-NBA-derived DNA adducts. High performance liquid chromatography (HPLC) with ultraviolet (UV) detection was employed for the separation and characterization of 2-NBA and 3-NBA metabolites formed by hepatic microsomes of rats and mice under the anaerobic and aerobic conditions. Microsomal systems isolated from the liver of the control (untreated) rats and rats pretreated with Sudan I, β-naphthoflavone (β-NF), phenobarbital (PB), ethanol and pregnenolon 16α-carbonitrile (PCN), the inducers of cytochromes P450 (CYP) 1A1, 1A1/2, 2B, 2E1 and 3A, respectively, were used in this study. Microsomes of mouse models, a control mouse line (wild-type, WT) and Hepatic Cytochrome P450 Reductase Null (HRN) mice with deleted gene of NADPH:CYP reductase in the liver, thus absenting this enzyme in their livers, were also employed. To detect and quantify the 2-NBA- and 3-NBA-derived DNA adducts, the 32P postlabeling technique was used. Both reductive metabolite of 3-NBA, 3-aminobenzanthrone (3-ABA), found to be formed predominantly under the anaerobic conditions, and two 3-NBA oxidative metabolites, whose structures have not yet been investigated, were formed by several microsomal systems used in the study. Whereas a 3-NBA reductive metabolite

  20. Metabolite Profiles of Diabetes Risk

    OpenAIRE

    Gerszten, Robert E.

    2013-01-01

    Metabolic diseases present particular difficulty for clinicians because they are often present for years before becoming clinically apparent. We investigated whether metabolite profiles can predict the development of diabetes in the Framingham Heart Study. Five branched-chain and aromatic amino acids had highly-significant associations with future diabetes, while a combination of three amino acids strongly predicted future diabetes by up to 12 years (>5-fold increased risk for individuals in ...

  1. Metabolites in vertebrate Hedgehog signaling.

    Science.gov (United States)

    Roberg-Larsen, Hanne; Strand, Martin Frank; Krauss, Stefan; Wilson, Steven Ray

    2014-04-11

    The Hedgehog (HH) signaling pathway is critical in embryonic development, stem cell biology, tissue homeostasis, chemoattraction and synapse formation. Irregular HH signaling is associated with a number of disease conditions including congenital disorders and cancer. In particular, deregulation of HH signaling has been linked to skin, brain, lung, colon and pancreatic cancers. Key mediators of the HH signaling pathway are the 12-pass membrane protein Patched (PTC), the 7-pass membrane protein Smoothened (SMO) and the GLI transcription factors. PTC shares homology with the RND family of small-molecule transporters and it has been proposed that it interferes with SMO through metabolites. Although a conclusive picture is lacking, substantial efforts are made to identify and understand natural metabolites/sterols, including cholesterol, vitamin D3, oxysterols and glucocorticoides, that may be affected by, or influence the HH signaling cascade at the level of PTC and SMO. In this review we will elaborate the role of metabolites in HH signaling with a focus on oxysterols, and discuss advancements in modern analytical approaches in the field. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Can creatine supplementation form carcinogenic heterocyclic amines in humans?

    Science.gov (United States)

    Pereira, Renato Tavares dos Santos; Dörr, Felipe Augusto; Pinto, Ernani; Solis, Marina Yazigi; Artioli, Guilherme Giannini; Fernandes, Alan Lins; Murai, Igor Hisashi; Dantas, Wagner Silva; Seguro, Antônio Carlos; Santinho, Mirela Aparecida Rodrigues; Roschel, Hamilton; Carpentier, Alain; Poortmans, Jacques Remi; Gualano, Bruno

    2015-01-01

    Abstract Creatine supplementation has been associated with increased cancer risk. In fact, there is evidence indicating that creatine and/or creatinine are important precursors of carcinogenic heterocyclic amines (HCAs). The present study aimed to investigate the acute and chronic effects of low- and high-dose creatine supplementation on the production of HCAs in healthy humans (i.e. 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx),  2-amino-(1,6-dimethylfuro[3,2-e]imidazo[4,5-b])pyridine (IFP) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx)). This was a non-counterbalanced single-blind crossover study divided into two phases, in which low- and high-dose creatine protocols were tested. After acute (1 day) and chronic supplementation (30 days), the HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx were assessed through a newly developed HPLC–MS/MS method. Dietary HCA intake and blood and urinary creatinine were also evaluated. Out of 576 assessments performed (from 149 urine samples), only nine (3 from creatine and 6 from placebo) showed quantifiable levels of HCAs (8-MeIQx: n = 3; 4,8-DiMeIQx: n = 2; PhIP: n = 4). Individual analyses revealed that diet rather than creatine supplementation was the main responsible factor for HCA formation in these cases. This study provides compelling evidence that both low and high doses of creatine supplementation, given either acutely or chronically, did not cause increases in the carcinogenic HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx in healthy subjects. These findings challenge the long-existing notion that creatine supplementation could potentially increase the risk of cancer by stimulating the formation of these mutagens. Key points There is a long-standing concern that creatine supplementation could be associated with cancer, possibly by facilitating the formation of carcinogenic heterocyclic amines (HCAs). This study provides compelling evidence

  3. 78 FR 44117 - Notice of a Public Comment Period on the Draft IRIS Carcinogenicity Assessment for Ethylene Oxide

    Science.gov (United States)

    2013-07-23

    ... Public Comment Period on the Draft IRIS Carcinogenicity Assessment for Ethylene Oxide AGENCY... Carcinogenicity of Ethylene Oxide'' (EPA/635/R-13/128a) and on the draft peer review charge questions. The draft... on the draft Evaluation of the Inhalation Carcinogenicity of Ethylene Oxide and on the draft peer...

  4. INTEGRATION OF QSAR AND SAR METHODS FOR THE MECHANISTIC INTERPRETATION OF PREDICTIVE MODELS FOR CARCINOGENICITY

    Directory of Open Access Journals (Sweden)

    Natalja Fjodorova

    2012-07-01

    Full Text Available The knowledge-based Toxtree expert system (SAR approach was integrated with the statistically based counter propagation artificial neural network (CP ANN model (QSAR approach to contribute to a better mechanistic understanding of a carcinogenicity model for non-congeneric chemicals using Dragon descriptors and carcinogenic potency for rats as a response. The transparency of the CP ANN algorithm was demonstrated using intrinsic mapping technique specifically Kohonen maps. Chemical structures were represented by Dragon descriptors that express the structural and electronic features of molecules such as their shape and electronic surrounding related to reactivity of molecules. It was illustrated how the descriptors are correlated with particular structural alerts (SAs for carcinogenicity with recognized mechanistic link to carcinogenic activity. Moreover, the Kohonen mapping technique enables one to examine the separation of carcinogens and non-carcinogens (for rats within a family of chemicals with a particular SA for carcinogenicity. The mechanistic interpretation of models is important for the evaluation of safety of chemicals.

  5. Approaches to the risk assessment of genotoxic carcinogens in food: a critical appraisal.

    Science.gov (United States)

    O'Brien, J; Renwick, A G; Constable, A; Dybing, E; Müller, D J G; Schlatter, J; Slob, W; Tueting, W; van Benthem, J; Williams, G M; Wolfreys, A

    2006-10-01

    The present paper examines the particular difficulties presented by low levels of food-borne DNA-reactive genotoxic carcinogens, some of which may be difficult to eliminate completely from the diet, and proposes a structured approach for the evaluation of such compounds. While the ALARA approach is widely applicable to all substances in food that are both carcinogenic and genotoxic, it does not take carcinogenic potency into account and, therefore, does not permit prioritisation based on potential risk or concern. In the absence of carcinogenicity dose-response data, an assessment based on comparison with an appropriate threshold of toxicological concern may be possible. When carcinogenicity data from animal bioassays are available, a useful analysis is achieved by the calculation of margins of exposure (MOEs), which can be used to compare animal potency data with human exposure scenarios. Two reference points on the dose-response relationship that can be used for MOE calculation were examined; the T25 value, which is derived from linear extrapolation, and the BMDL10, which is derived from mathematical modelling of the dose-response data. The above approaches were applied to selected food-borne genotoxic carcinogens. The proposed approach is applicable to all substances in food that are DNA-reactive genotoxic carcinogens and enables the formulation of appropriate semi-quantitative advice to risk managers.

  6. Enhanced replication of UV-damaged Simian virus 40 DNA in carcinogen-treated mammalian cells

    International Nuclear Information System (INIS)

    Maga, J.A.

    1983-01-01

    The replication of UV-damaged Simian virus 40 (SV40) in carcinogen-treated monkey cells has been studied to elucidate the mechanism of carcinogen-enhanced reactivation. Carcinogen enhanced reactivation is the observed increase in UV-irradiated virus survival in host cells treated with low doses of carcinogen compared to UV-irradiated virus survival in untreated hosts. Carcinogen treatment of monkey kidney cells with either N-acetoxy-2-acetylaminofluorene (AAAF) or UV radiation leads to an enhanced capacity to replicate UV-damaged virus during the first round of infection. To further define the mechanism leading to enhanced replication, a detailed biochemical analysis of replication intermediates in carcinogen-treated cells was performed. Several conclusions can be drawn. First enhanced replication can be observed in the first four rounds of replication after UV irradiation of viral templates. The second major finding is that the relaxed circular intermediate model proposed for the replication of UV-damaged templates in untreated cells appears valid for replication of UV-damaged templates in carcinogen-treated cells. Possible mechanisms and the supporting evidence are discussed and future experiments outlined

  7. Carcinogenicity of petroleum lubricating oil distillates: effects of solvent refining, hydroprocessing, and blending.

    Science.gov (United States)

    Halder, C A; Warne, T M; Little, R Q; Garvin, P J

    1984-01-01

    Certain refining processes were investigated to determine their influence on the dermal carcinogenic activity of petroleum-derived lubricating oil distillates. Specifically, the effects of solvent refining, hydroprocessing, a combination of both processes, and the blending of oils processed using each technique were evaluated in standard mouse skin-painting bioassays. The refining process used as well as the level or severity of treatment greatly influenced the carcinogenic outcome of processed lubricating oils. Solvent refining at severities normally used appeared to eliminate carcinogenicity. In contrast, hydroprocessing alone at mild levels of treatment was successful only in reducing the carcinogenic potency; severe hydroprocessing conditions were necessary to eliminate carcinogenic activity without the use of additional refining processes. Carcinogenic activity could also be eliminated by following moderate solvent refining with mild hydroprocessing. Blending of hydroprocessed oils with solvent-refined oils resulted in a substantial reduction or even elimination of carcinogenic activity. However, the degree of protection obtained varied with the particular distillates used and appeared largely dependent on the inherent biological activity of the hydroprocessed oil.

  8. Non-covalent interactions of the carcinogen (+)-anti-BPDE with exon 1 of the human K-ras proto-oncogene

    Science.gov (United States)

    Rodriguez, Jorge H.; Deligkaris, Christos

    2013-03-01

    Investigating the complementary, but different, effects of physical (non-covalent) and chemical (covalent) mutagen-DNA and carcinogen-DNA interactions is important for understanding possible mechanisms of development and prevention of mutagenesis and carcinogenesis. A highly mutagenic and carcinogenic metabolite of the polycyclic aromatic hydrocarbon benzo[ α]pyrene, namely (+)-anti-BPDE, is known to undergo both physical and chemical complexation with DNA. The major covalent adduct, a promutagenic, is known to be an external (+)-trans-anti-BPDE-N2-dGuanosine configuration whose origins are not fully understood. Thus, it is desirable to study the mechanisms of external non-covalent BPDE-DNA binding and their possible relationships to external covalent trans adduct formation. We present a detailed codon-by-codon computational study of the non-covalent interactions of (+)-anti-BPDE with DNA which explains and correctly predicts preferential (+)-anti-BPDE binding at minor groove guanosines. Due to its relevance to carcinogenesis, the interaction of (+)-anti-BPDE with exon 1 of the human K-ras gene has been studied in detail. Present address: Department of Physics, Drury University

  9. Ultimate architecture

    CERN Multimedia

    Jencks, Charles

    2007-01-01

    "European physics hothouse CERN recently unveiled Atlas, the world's most powerful particle detector, which it will use to search for the fundamental building blocks of nature from May next year. Charles Jencks describes the experience of getting up clsoe to the engineering marvel that could en up creating a mini-black hole."(5 pages with photos).

  10. Ultimate energy

    International Nuclear Information System (INIS)

    1994-01-01

    An explanation is given of the complexity faced by the scientific researcher in an effort to achieve fusion power. Outlines the theory and current experiments being pursued in this complex project, including visits to five major fusion research laboratories, and interviews with physicists

  11. Formation of glutathione conjugates by reactive metabolites of vinylidene chloride in microsomes and isolated hepatocytes

    International Nuclear Information System (INIS)

    Liebler, D.C.; Meredith, M.J.; Guengerich, F.P.

    1985-01-01

    Oxidation of the vinyl halide carcinogen and hepatotoxin vinylidene chloride (VDC) by microsomal cytochrome P-450 yields 2,2-dichloroacetaldehyde, 2-chloroacetyl chloride, 2-chloroacetic acid, and 1,1-dichloroethylene oxide. The roles of these metabolites in covalent modification of proteins and reduced glutathione (GSH) were examined. 2-Chloroacetyl chloride reacted with model thiols at least 10(3)-fold faster than did 1,1-dichloroethylene oxide and at least 10(5)-fold faster than did 2,2-dichloroacetaldehyde or 2-chloroacetic acid. Microsomal covalent binding of [ 14 C]VDC was inhibited by GSH but not by lysine, suggesting that protein thiols, rather than amino groups, are major targets. Liver microsomes catalyzed the formation of three GSH:VDC metabolite conjugates, identified as S-(2,2-dichloro-1-hydroxy)ethylglutathione, 2-(S-glutathionyl)acetate, and S-(2-glutathionyl)acetylglutathione, a novel conjugate containing both stable (thioether) and labile (thioester) linkages. The latter two conjugates also were formed in isolated rat hepatocytes and measurable amounts of 2-(S-glutathionyl)acetate were released into the incubation medium. Both 2-(S-glutathionyl)acetate and S-(2-glutathionyl)acetylglutathione were formed with [ 35 S]GSH added to the hepatic medium, indicating that reactive VDC metabolites are capable of crossing the plasma membrane to react with extracellular targets. Unlabeled S-(2-glutathionyl)-acetylglutathione underwent carbonyl substitution with added [ 35 S]GSH, suggesting that this conjugate may participate in modification of protein thiols. This conjugate also underwent hydrolysis with a half-life of approximately 3 hr. GSH:VDC metabolite conjugates may serve as accessible models for labile covalent adducts formed between VDC metabolites and protein thiols

  12. Identification of Radiation Effects on Carcinogenic Food Estimated by Ames Test

    International Nuclear Information System (INIS)

    Afifi, M.; Eid, I.; El - Nagdy, M.; Zaher, R.; Abd El-Karem, H.; Abd EL Karim, A.

    2016-01-01

    A major concern in studies related to carcinogenesis is the exposure to the exogenous carcinogens that may occur in food in both natural and polluted human environments. The purpose of the present study is to examine some of food products by Ames test to find out if food products carcinogenic then expose food to gamma radiation to find out the effect of radiation on it as a treatment. In this study, the food samples were examined by Ames test (Salmonella typhimurium mutagenicity test) to find out that a food product could be carcinogenic or highly mutated. Testing of chemicals for mutagenicity is based on the knowledge that a substance which is mutagenic in the bacterium is more likely than not to be a carcinogen in laboratory animals, and thus , by extension, present a risk of cancer to humans. After that food products that showed mutagenicity exposed to gamma radiation at different doses to examine the effect of gamma radiation on food products. This study represent γ radiation effect on carcinogenic food by using Ames test in the following steps: Detect food by Ames test using Salmonella typhimurium strains in which the colony count /plate for each food sample will show if food is slightly mutated or highly mutated or carcinogenic. If food is highly mutated or carcinogenic with high number of colonies /plate, then the carcinogenic food or highly mutated food exposed to different doses of radiation The applied doses in this study were 0, 2.5, 5, and 10 (KGy). Detect the radiation effect on food samples by Ames test after irradiation. The study shows that mutated and carcinogenic food products estimated by Ames test could be treated by irradiation

  13. Urinary polycyclic aromatic hydrocarbon metabolites among 3-year-old children from Krakow, Poland.

    Science.gov (United States)

    Sochacka-Tatara, Elżbieta; Majewska, Renata; Perera, Frederica P; Camann, David; Spengler, John; Wheelock, Kylie; Sowa, Agata; Jacek, Ryszard; Mróz, Elżbieta; Pac, Agnieszka

    2018-07-01

    Polycyclic aromatic hydrocarbons (PAHs) are widespread in the environment and can adversely affect human health. The aim of the present study is to describe the level of PAHs exposure in children living in Kraków, one of the most polluted cities in Poland, and to determine the relationship of urinary biomarkers with environmental PAHsexposure. Urinary monohydroxy metabolites (OH-PAHs) of 20 PAHs were assessed in 218 three-year old children, of which only 10 were present in nearly all the samples: monohydroxy metabolites of naphthalene, fluorene, phenantrene and pyrene. Of the metabolites analyzed, hydroxynaphthalenes were predominant and constituted almost 73% of total excreted OH-PAHs, while 1-OH-PYRene was the least abundant (2.3% of total OH-PAHs). All measured urinary OH-PAHs were statistically significantly correlated with each other (R = 0.165-0.880) but the highest correlation coefficients with other individual OH-PAHs and with total OH-PAHs were observed for 2-OH-FLUOR. Children exposed at home to environmental tobacco smoke (ETS) had higher concentrations of fluorene and pyrene urinary metabolites compared to those without ETS exposure; and those exposed to gas-based appliances used for cooking or heating water had higher levels of fluorene and phenanthrene metabolites than children not exposed. The use of coal, wood or oil for heating was associated with elevated levels of 1-OH-PYRene. Urinary PAHs metabolites only modestly reflect high molecular weight carcinogenic PAHs exposures such as those monitored in air in the present study. None of the measured PAHs metabolites was correlated with airborne PM 2.5 and only two were slightly correlated with measured higher molecular mass airborne PAHs. The average concentrations of these specific metabolites in Polish children were much higher than observed in other pediatric populations living in developed countries. Our findings suggest that to capture various sources of PAHs, in addition to 1-OH

  14. Engineering Microbial Metabolite Dynamics and Heterogeneity.

    Science.gov (United States)

    Schmitz, Alexander C; Hartline, Christopher J; Zhang, Fuzhong

    2017-10-01

    As yields for biological chemical production in microorganisms approach their theoretical maximum, metabolic engineering requires new tools, and approaches for improvements beyond what traditional strategies can achieve. Engineering metabolite dynamics and metabolite heterogeneity is necessary to achieve further improvements in product titers, productivities, and yields. Metabolite dynamics, the ensemble change in metabolite concentration over time, arise from the need for microbes to adapt their metabolism in response to the extracellular environment and are important for controlling growth and productivity in industrial fermentations. Metabolite heterogeneity, the cell-to-cell variation in a metabolite concentration in an isoclonal population, has a significant impact on ensemble productivity. Recent advances in single cell analysis enable a more complete understanding of the processes driving metabolite heterogeneity and reveal metabolic engineering targets. The authors present an overview of the mechanistic origins of metabolite dynamics and heterogeneity, why they are important, their potential effects in chemical production processes, and tools and strategies for engineering metabolite dynamics and heterogeneity. The authors emphasize that the ability to control metabolite dynamics and heterogeneity will bring new avenues of engineering to increase productivity of microbial strains. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Classification of weakly carcinogenic human papillomavirus types: addressing the limits of epidemiology at the borderline

    Directory of Open Access Journals (Sweden)

    Buonaguro Franco M

    2009-06-01

    Full Text Available Abstract Virtually all cases of cervical cancer are caused by persistent infections with a restricted set of human papillomaviruses (HPV. Some HPV types, like HPV16 and HPV18, are clear and powerful carcinogens. However, the categorization of the most weakly carcinogenic HPV types is extremely challenging. The decisions are important for screening test and vaccine development. This article describes for open discussion an approach recently taken by a World Health Organization International Agency for Research on Cancer (IARC Monographs Working Group to re-assess the carcinogenicity of different HPV types.

  16. 75 FR 76746 - Agency Information Collection Activities: Declaration of Ultimate Consignee That Articles Were...

    Science.gov (United States)

    2010-12-09

    ... Activities: Declaration of Ultimate Consignee That Articles Were Exported for Temporary Scientific or... That Articles Were Exported for Temporary Scientific or Educational Purposes. This is a proposed... forms of information. Title: Declaration of Ultimate Consignee That Articles Were Exported for Temporary...

  17. 7 CFR 4280.21 - Eligible REDG Ultimate Recipients and Projects.

    Science.gov (United States)

    2010-01-01

    ... care providers; (5) Projects that utilize Advanced Telecommunications or computer networks to... 7 Agriculture 15 2010-01-01 2010-01-01 false Eligible REDG Ultimate Recipients and Projects. 4280... Economic Development Loan and Grant Programs § 4280.21 Eligible REDG Ultimate Recipients and Projects. The...

  18. 78 FR 55117 - Ultimate Heat Sink for Nuclear Power Plants; Draft Regulatory Guide

    Science.gov (United States)

    2013-09-09

    ... NUCLEAR REGULATORY COMMISSION [NRC-2013-0203] Ultimate Heat Sink for Nuclear Power Plants; Draft... (DG), DG-1275, ``Ultimate Heat Sink for Nuclear Power Plants.'' This regulatory guide (RG) describes methods and procedures acceptable to the NRC staff that nuclear power plant facility licensees and...

  19. Advances in Carcinogenic Metal Toxicity and Potential Molecular Markers

    Directory of Open Access Journals (Sweden)

    Preeyaporn Koedrith

    2011-12-01

    Full Text Available Metal compounds such as arsenic, cadmium, chromium, cobalt, lead, mercury, and nickel are classified as carcinogens affecting human health through occupational and environmental exposure. However, the underlying mechanisms involved in tumor formation are not well clarified. Interference of metal homeostasis may result in oxidative stress which represents an imbalance between production of free radicals and the system’s ability to readily detoxify reactive intermediates. This event consequently causes DNA damage, lipid peroxidation, protein modification, and possibly symptomatic effects for various diseases including cancer. This review discusses predominant modes of action and numerous molecular markers. Attention is paid to metal-induced generation of free radicals, the phenomenon of oxidative stress, damage to DNA, lipid, and proteins, responsive signal transduction pathways with major roles in cell growth and development, and roles of antioxidant enzymatic and DNA repair systems. Interaction of non-enzymatic antioxidants (carotenoids, flavonoids, glutathione, selenium, vitamin C, vitamin E, and others with cellular oxidative stress markers (catalase, glutathione peroxidase, and superoxide dismutase as well as certain regulatory factors, including AP-1, NF-κB, Ref-1, and p53 is also reviewed. Dysregulation of protective pathways, including cellular antioxidant network against free radicals as well as DNA repair deficiency is related to oncogenic stimulation. These observations provide evidence that emerging oxidative stress-responsive regulatory factors and DNA repair proteins are putative predictive factors for tumor initiation and progression.

  20. Influence of cracks and pitting corrosion on residual ultimate strength of stiffened plates

    Directory of Open Access Journals (Sweden)

    ZHANG Jing

    2018-02-01

    Full Text Available [Objectives] Ships and offshore platforms serve in the harsh sea environment for a long time. Cracks and pitting corrosion will occur in such a structure and the damage will affect its ultimate strength.[Methods] To investigate the influence of cracks and pitting corrosion on ultimate bearing capacity, the ultimate strength of a structure under axial compression is studied by using a nonlinear finite element. The mesh size of a stiffened plate with cracks and pitting corrosion is first discussed. Then the influence of the relative positions of cracks and pitting corrosion, number of corrosion points and crack length impact on the residual ultimate strength of damaged stiffened plates is discussed via a series of calculations.[Results] The results indicate that the increase in crack length and pitting corrosion significantly decreases the ultimate strength of a stiffened plate. [Conclusions] This provides a useful reference for designing and maintaining ships and offshore structures in their life cycles.

  1. Ultimate capacity and influenced factors analysis of nuclear RC containment subjected to internal pressure

    International Nuclear Information System (INIS)

    Song Chenning; Hou Gangling; Zhou Guoliang

    2014-01-01

    Ultimate compressive bearing capacity, influenced factors and its rules of nuclear RC containment are key problems of safety assessment, accident treatment and structure design, etc. Ultimate compressive bearing capacity of nuclear RC containment is shown by concrete damaged plasticity model and steel double liner model of ABAQUS. The study shows that the concrete of nuclear RC containment cylinder wall becomes plastic when the internal pressure is up to 0.87 MPa, the maximum tensile strain of steel liner exceeds 3000 × 10 6 and nuclear RC containment reaches ultimate status when the internal pressure is up to 1.02 MPa. The result shows that nuclear RC containment is in elastic condition under the design internal pressure and the bearing capacity meets requirement. Prestress and steel liner play key parts in the ultimate internal pressure and failure mode of nuclear RC containment. The study results have value for the analysis of ultimate compressive bearing capacity, structure design and safety assessment. (authors)

  2. Editor's Highlight: High-Throughput Functional Genomics Identifies Modulators of TCE Metabolite Genotoxicity and Candidate Susceptibility Genes.

    Science.gov (United States)

    De La Rosa, Vanessa Y; Asfaha, Jonathan; Fasullo, Michael; Loguinov, Alex; Li, Peng; Moore, Lee E; Rothman, Nathaniel; Nakamura, Jun; Swenberg, James A; Scelo, Ghislaine; Zhang, Luoping; Smith, Martyn T; Vulpe, Chris D

    2017-11-01

    Trichloroethylene (TCE), an industrial chemical and environmental contaminant, is a human carcinogen. Reactive metabolites are implicated in renal carcinogenesis associated with TCE exposure, yet the toxicity mechanisms of these metabolites and their contribution to cancer and other adverse effects remain unclear. We employed an integrated functional genomics approach that combined functional profiling studies in yeast and avian DT40 cell models to provide new insights into the specific mechanisms contributing to toxicity associated with TCE metabolites. Genome-wide profiling studies in yeast identified the error-prone translesion synthesis (TLS) pathway as an import mechanism in response to TCE metabolites. The role of TLS DNA repair was further confirmed by functional profiling in DT40 avian cell lines, but also revealed that TLS and homologous recombination DNA repair likely play competing roles in cellular susceptibility to TCE metabolites in higher eukaryotes. These DNA repair pathways are highly conserved between yeast, DT40, and humans. We propose that in humans, mutagenic TLS is favored over homologous recombination repair in response to TCE metabolites. The results of these studies contribute to the body of evidence supporting a mutagenic mode of action for TCE-induced renal carcinogenesis mediated by reactive metabolites in humans. Our approach illustrates the potential for high-throughput in vitro functional profiling in yeast to elucidate toxicity pathways (molecular initiating events, key events) and candidate susceptibility genes for focused study. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Epigenome targeting by probiotic metabolites

    Directory of Open Access Journals (Sweden)

    Licciardi Paul V

    2010-12-01

    Full Text Available Abstract Background The intestinal microbiota plays an important role in immune development and homeostasis. A disturbed microbiota during early infancy is associated with an increased risk of developing inflammatory and allergic diseases later in life. The mechanisms underlying these effects are poorly understood but are likely to involve alterations in microbial production of fermentation-derived metabolites, which have potent immune modulating properties and are required for maintenance of healthy mucosal immune responses. Probiotics are beneficial bacteria that have the capacity to alter the composition of bacterial species in the intestine that can in turn influence the production of fermentation-derived metabolites. Principal among these metabolites are the short-chain fatty acids butyrate and acetate that have potent anti-inflammatory activities important in regulating immune function at the intestinal mucosal surface. Therefore strategies aimed at restoring the microbiota profile may be effective in the prevention or treatment of allergic and inflammatory diseases. Presentation of the hypothesis Probiotic bacteria have diverse effects including altering microbiota composition, regulating epithelial cell barrier function and modulating of immune responses. The precise molecular mechanisms mediating these probiotic effects are not well understood. Short-chain fatty acids such as butyrate are a class of histone deacetylase inhibitors important in the epigenetic control of host cell responses. It is hypothesized that the biological function of probiotics may be a result of epigenetic modifications that may explain the wide range of effects observed. Studies delineating the effects of probiotics on short-chain fatty acid production and the epigenetic actions of short-chain fatty acids will assist in understanding the association between microbiota and allergic or autoimmune disorders. Testing the hypothesis We propose that treatment with

  4. Metabolite Profiling of Red Sea Corals

    KAUST Repository

    Ortega, Jovhana Alejandra

    2016-12-01

    Looking at the metabolite profile of an organism provides insights into the metabolomic state of a cell and hence also into pathways employed. Little is known about the metabolites produced by corals and their algal symbionts. In particular, corals from the central Red Sea are understudied, but interesting study objects, as they live in one of the warmest and most saline environments and can provide clues as to the adjustment of corals to environmental change. In this study, we applied gas chromatography – mass spectrometry (GC–MS) metabolite profiling to analyze the metabolic profile of four coral species and their associated symbionts: Fungia granulosa, Acropora hemprichii, Porites lutea, and Pocillopora verrucosa. We identified and quantified 102 compounds among primary and secondary metabolites across all samples. F. granulosa and its symbiont showed a total of 59 metabolites which were similar to the 51 displayed by P. verrucosa. P. lutea and A. hemprichii both harbored 40 compounds in conjunction with their respective isolated algae. Comparing across species, 28 metabolites were exclusively present in algae, while 38 were exclusive to corals. A principal component and cluster analyses revealed that metabolite profiles clustered between corals and algae, but each species harbored a distinct catalog of metabolites. The major classes of compounds were carbohydrates and amino acids. Taken together, this study provides a first description of metabolites of Red Sea corals and their associated symbionts. As expected, the metabolites of coral hosts differ from their algal symbionts, but each host and algal species harbor a unique set of metabolites. This corroborates that host-symbiont species pairs display a fine-tuned complementary metabolism that provide insights into the specific nature of the symbiosis. Our analysis also revealed aquatic pollutants, which suggests that metabolite profiling might be used for monitoring pollution levels and assessing

  5. Determination of potentially carcinogenic compounds in food : trace analysis of vinylchloride, vinylidenechloride, acrylonitrile, epichlorohydrin and diethylpyrocarbonate

    NARCIS (Netherlands)

    Lierop, van J.B.H.

    1979-01-01

    Toxicological evidence shows that some monomers present in packaging materials may be carcinogenic. These monomers, notably vinylchloride, vinylidenechloride, acrylonitrile and epichlorohydrin, may migrate from the packaging material into the food. Therefore, severe limits are set to the contents of

  6. AI AND SAR APPROACHES FOR PREDICTING CHEMICAL CARCINOGENICITY: SURVEY AND STATUS REPORT

    Science.gov (United States)

    A wide variety of artificial intelligence (AI) and structure-activity relationship (SAR approaches have been applied to tackling the general problem of predicting rodent chemical carcinogenicity. Given the diversity of chemical structures and mechanisms relative to this endpoin...

  7. A review of biosensing techniques for detection of trace carcinogen contamination in food products.

    Science.gov (United States)

    Li, Zhanming; Yu, Yue; Li, Zhiliang; Wu, Tao

    2015-04-01

    Carcinogen contaminations in the food chain, for example heavy metal ions, pesticides, acrylamide, and mycotoxins, have caused serious health problems. A major objective of food-safety research is the identification and prevention of exposure to these carcinogens, because of their impossible-to-reverse tumorigenic effects. However, carcinogen detection is difficult because of their trace-level presence in food. Thus, reliable and accurate separation and determination methods are essential to protect food safety and human health. This paper summarizes the state of the art in separation and determination methods for analyzing carcinogen contamination, especially the advances in biosensing methods. Furthermore, the application of promising technology including nanomaterials, imprinted polymers, and microdevices is detailed. Challenges and perspectives are also discussed.

  8. OSHA Confronts Carcinogens in the Workplace as Inflation Fighters Confront OSHA.

    Science.gov (United States)

    Heller, Ilene

    1978-01-01

    Discusses the apparently opposing forces of worker safety, as represented by the Occupational Safety and Health Administration (OSHA), and economic inflation spawned by expensive industrial processes needed to limit the emission of carcinogens. (CP)

  9. Carcinogenicity and Immnotoxicity of Embedded Depleted Uranium and Heavy-Metal Tungsten Alloy in Rodents

    National Research Council Canada - National Science Library

    Miller, Alexandra

    2002-01-01

    .... We hypothesize that long-term chronic exposure to embedded DU and HMTA initiates changes in normal immune function that will eventually result in a carcinogenic response characterized by both tumor...

  10. Predictive Models for Carcinogenicity and Mutagenicity: Frameworks,State-of-the-Art, and Perspectives

    Science.gov (United States)

    Mutagenicity and carcinogenicity are endpoints of major environmental and regulatory concern. These endpoints are also important targets for development of alternative methods for screening and prediction due to the large number of chemicals of potential concern and the tremendou...

  11. On the International Agency for Research on Cancer classification of glyphosate as a probable human carcinogen.

    Science.gov (United States)

    Tarone, Robert E

    2018-01-01

    The recent classification by International Agency for Research on Cancer (IARC) of the herbicide glyphosate as a probable human carcinogen has generated considerable discussion. The classification is at variance with evaluations of the carcinogenic potential of glyphosate by several national and international regulatory bodies. The basis for the IARC classification is examined under the assumptions that the IARC criteria are reasonable and that the body of scientific studies determined by IARC staff to be relevant to the evaluation of glyphosate by the Monograph Working Group is sufficiently complete. It is shown that the classification of glyphosate as a probable human carcinogen was the result of a flawed and incomplete summary of the experimental evidence evaluated by the Working Group. Rational and effective cancer prevention activities depend on scientifically sound and unbiased assessments of the carcinogenic potential of suspected agents. Implications of the erroneous classification of glyphosate with respect to the IARC Monograph Working Group deliberative process are discussed.

  12. of Several Organophosphorus Insecticide Metabolites

    Directory of Open Access Journals (Sweden)

    Russell L. Carr

    2015-01-01

    Full Text Available Paraoxonase (PON1 is a calcium dependent enzyme that is capable of hydrolyzing organophosphate anticholinesterases. PON1 activity is present in most mammals and previous research established that PON1 activity differs depending on the species. These studies mainly used the organophosphate substrate paraoxon, the active metabolite of the insecticide parathion. Using serum PON1 from different mammalian species, we compared the hydrolysis of paraoxon with the hydrolysis of the active metabolites (oxons of two additional organophosphorus insecticides, methyl parathion and chlorpyrifos. Paraoxon hydrolysis was greater than that of methyl paraoxon, but the level of activity between species displayed a similar pattern. Regardless of the species tested, the hydrolysis of chlorpyrifos-oxon was significantly greater than that of paraoxon or methyl paraoxon. These data indicate that chlorpyrifos-oxon is a better substrate for PON1 regardless of the species. The pattern of species differences in PON1 activity varied with the change in substrate to chlorpyrifos-oxon from paraoxon or methyl paraoxon. For example, the sex difference observed here and reported elsewhere in the literature for rat PON1 hydrolysis of paraoxon was not present when chlorpyrifos-oxon was the substrate.

  13. A study on nonlinear behavior of reactor containment structures during ultimate accident condition(I)

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Hoon; Kim, Young Jin; Park, Joo Yeon [Youngdong Univ., Yeongdong (Korea, Republic of)] (and others)

    2003-03-15

    In this study, the following scope and contents are established for first year's study of determining ultimate pressure capacity of CANDU-type reactor containment. State-of-arts on the prediction of the ultimate pressure capacity of prestressed concrete reactor containment. Comparative study on structural characteristics and analysis model of CANDU-type reactor containment. State-of-arts on evaluation method of the ultimate pressure capacity of prestressed concrete reactor containment. Enhancement of evaluation method of the ultimate pressure capacity for PWR containment structure. In order to determine a realistic lower bound of a typical reactor containment structural capacity for internal pressure, modelling techniques and analytical investigation to predict its non-linear behavior up to ultimate capacity are required. Especially, the in-depth evaluation of modeling technique and analysis procedure for determining ultimate pressure capacity of CANDU-type reactor containment is required. Therefore, modelling techniques and analytical investigation to predict its non-linear behavior up to ultimate pressure capacity of CANDU-type reactor containment for internal pressure will be suggested in this study.

  14. A study on nonlinear behavior of reactor containment structures during ultimate accident condition(I)

    International Nuclear Information System (INIS)

    Kim, Sun Hoon; Kim, Young Jin; Park, Joo Yeon

    2003-03-01

    In this study, the following scope and contents are established for first year's study of determining ultimate pressure capacity of CANDU-type reactor containment. State-of-arts on the prediction of the ultimate pressure capacity of prestressed concrete reactor containment. Comparative study on structural characteristics and analysis model of CANDU-type reactor containment. State-of-arts on evaluation method of the ultimate pressure capacity of prestressed concrete reactor containment. Enhancement of evaluation method of the ultimate pressure capacity for PWR containment structure. In order to determine a realistic lower bound of a typical reactor containment structural capacity for internal pressure, modelling techniques and analytical investigation to predict its non-linear behavior up to ultimate capacity are required. Especially, the in-depth evaluation of modeling technique and analysis procedure for determining ultimate pressure capacity of CANDU-type reactor containment is required. Therefore, modelling techniques and analytical investigation to predict its non-linear behavior up to ultimate pressure capacity of CANDU-type reactor containment for internal pressure will be suggested in this study

  15. Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review

    Science.gov (United States)

    Chappell, Grace; Pogribny, Igor P.; Guyton, Kathryn Z.; Rusyn, Ivan

    2016-01-01

    Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although the epigenome and genome may be equally important in carcinogenicity, the genotoxicity of chemical agents and exposure-related transcriptomic responses have been more thoroughly studied and characterized. To better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints. Specifically, we searched for publications reporting epigenetic effects for the 28 agents and occupations included in Monograph Volume 100F of the International Agency for the Research on Cancer (IARC) that were classified as “carcinogenic to humans” (Group 1) with strong evidence of genotoxic mechanisms of carcinogenesis. We identified a total of 158 studies that evaluated epigenetic alterations for 12 of these 28 carcinogenic agents and occupations (1,3-butadiene, 4-aminobiphenyl, aflatoxins, benzene, benzidine, benzo[a]pyrene, coke production, formaldehyde, occupational exposure as a painter, sulfur mustard, and vinyl chloride). Aberrant DNA methylation was most commonly studied, followed by altered expression of non-coding RNAs and histone changes (totaling 85, 59 and 25 studies, respectively). For 3 carcinogens (aflatoxins, benzene and benzo[a]pyrene), 10 or more studies reported epigenetic effects. However, epigenetic studies were sparse for the remaining 9 carcinogens; for 4 agents, only 1 or 2 published reports were identified. While further research is needed to better identify carcinogenesis-associated epigenetic perturbations for many potential carcinogens, published reports on specific epigenetic endpoints can be systematically identified and increasingly incorporated in cancer hazard assessments. PMID:27234561

  16. Critical effective methods to detect genotoxic carcinogens and neoplasm-promoting agents.

    OpenAIRE

    Weisburger, J H; Williams, G M

    1991-01-01

    Neoplasia in fish can result from contamination of waters with carcinogens and promoters. Cancer in fish, therefore, is a possible indicator of cancer risk to man and serves as a guide to the need for preventive approaches involving improved means of waste disposal and environmental hygiene. Moreover, cancer in fish indicates that this important food source may be contaminated. Detection of genotoxic carcinogens to which fish are exposed can be achieved quickly and efficiently by carefully se...

  17. Quantitative structure activity relationship for the computational prediction of nitrocompounds carcinogenicity

    International Nuclear Information System (INIS)

    Morales, Aliuska Helguera; Perez, Miguel Angel Cabrera; Combes, Robert D.; Gonzalez, Maykel Perez

    2006-01-01

    Several nitrocompounds have been screened for carcinogenicity in rodents, but this is a lengthy and expensive process, taking two years and typically costing 2.5 million dollars, and uses large numbers of animals. There is, therefore, much impetus to develop suitable alternative methods. One possible way of predicting carcinogenicity is to use quantitative structure-activity relationships (QSARs). QSARs have been widely utilized for toxicity testing, thereby contributing to a reduction in the need for experimental animals. This paper describes the results of applying a TOPological substructural molecular design (TOPS-MODE) approach for predicting the rodent carcinogenicity of nitrocompounds. The model described 79.10% of the experimental variance, with a standard deviation of 0.424. The predictive power of the model was validated by leave-one-out validation, with a determination coefficient of 0.666. In addition, this approach enabled the contribution of different fragments to carcinogenic potency to be assessed, thereby making the relationships between structure and carcinogenicity to be transparent. It was found that the carcinogenic activity of the chemicals analysed was increased by the presence of a primary amine group bonded to the aromatic ring, a manner that was proportional to the ring aromaticity. The nitro group bonded to an aromatic carbon atom is a more important determinant of carcinogenicity than the nitro group bonded to an aliphatic carbon. Finally, the TOPS-MODE approach was compared with four other predictive models, but none of these could explain more than 66% of the variance in the carcinogenic potency with the same number of variables

  18. Gene discovery for the carcinogenic human liver fluke, Opisthorchis viverrini

    Directory of Open Access Journals (Sweden)

    Gasser Robin B

    2007-06-01

    Full Text Available Abstract Background Cholangiocarcinoma (CCA – cancer of the bile ducts – is associated with chronic infection with the liver fluke, Opisthorchis viverrini. Despite being the only eukaryote that is designated as a 'class I carcinogen' by the International Agency for Research on Cancer, little is known about its genome. Results Approximately 5,000 randomly selected cDNAs from the adult stage of O. viverrini were characterized and accounted for 1,932 contigs, representing ~14% of the entire transcriptome, and, presently, the largest sequence dataset for any species of liver fluke. Twenty percent of contigs were assigned GO classifications. Abundantly represented protein families included those involved in physiological functions that are essential to parasitism, such as anaerobic respiration, reproduction, detoxification, surface maintenance and feeding. GO assignments were well conserved in relation to other parasitic flukes, however, some categories were over-represented in O. viverrini, such as structural and motor proteins. An assessment of evolutionary relationships showed that O. viverrini was more similar to other parasitic (Clonorchis sinensis and Schistosoma japonicum than to free-living (Schmidtea mediterranea flatworms, and 105 sequences had close homologues in both parasitic species but not in S. mediterranea. A total of 164 O. viverrini contigs contained ORFs with signal sequences, many of which were platyhelminth-specific. Examples of convergent evolution between host and parasite secreted/membrane proteins were identified as were homologues of vaccine antigens from other helminths. Finally, ORFs representing secreted proteins with known roles in tumorigenesis were identified, and these might play roles in the pathogenesis of O. viverrini-induced CCA. Conclusion This gene discovery effort for O. viverrini should expedite molecular studies of cholangiocarcinogenesis and accelerate research focused on developing new interventions

  19. Non-carcinogenic late effects of ionizing radiation; human data

    International Nuclear Information System (INIS)

    Beebe, G.W.

    1979-01-01

    The late effects of ionizing radiation may be somatic effect or potential effect, about which such informations as follows are required: teratogenesis the disturbances in growth and development, cataracts, infertility, cytogenetic aberration, and accelerated aging. Although much is known about the nature of the malformations produced by ionizing radiation, and about the vulnerability of human embryonal and fetal tissues during various stages of organogenesis, the quantitative information is uncertain and incomplete. The data on A-bomb survivors were flawed by confounding radiation dose with nutritional and other influences caused by the disasters created by war-time bombings. If the effects of radiation are real, they are quite small for the dose below 100 rad (kerma), are confined to the children of pre-pubertal age at the time of exposure, and are of much less consequence for low-LET radiation than for high. Radiation-induced lenticular changes are of graded severity, and as for cataracts, the threshold is in the range from 600 to 1,000 rad of low-LET radiation, and perhaps 75 to 100 rad for fast neutrons; the average latent period is 2 to 7 years. The estimate of the RBE for neutrons is in the range from 2 to 10, and dose-dependent. Ionizing radiation has important effects on fertility only at very high dose. The relationship of the quantitative aspects of the biologic significance of chromosomal aberration in somatic cells to dose may provide an interesting parallel to the carcinogenic effect. For neutrons, the dose-response curve appears to be linear, at least for stable aberration. (Yamashita, S.)

  20. Anticarcinogenic effect of betel leaf extract against tobacco carcinogens.

    Science.gov (United States)

    Padma, P R; Lalitha, V S; Amonkar, A J; Bhide, S V

    1989-06-01

    Epidemiological studies have implicated that betel quid offers some protection to tobacco induced carcinogenesis. Earlier studies in our laboratory have shown betel leaf extract (BLE) to be antimutagenic against standard mutagens and tobacco-specific N'-nitrosamines (TSNA), N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In the present study, we have tested the anticarcinogenic effect of BLE using Swiss male mice. Two protocols of study were used to test this effect. In the first protocol, the effect of BLE was tested against the standard carcinogen benzo[a]pyrene (BP) using Wattenberg's stomach tumor model, Cancer Res., 41 (1981) 2820-2823. In this protocol, BLE inhibited the tumorigenicity of BP to a significant extent. In the second protocol, the effect of BLE against the two tobacco-specific nitrosamines, NNN and NNK was studied using long-term studies on Swiss male mice. The nitrosamines were administered on the tongues of the mice, while the BLE was supplied in drinking water. Two doses of NNN (22 mg and 72 mg) and one dose of NNK (22 mg) were used. In this study, it was observed that the number of tumor bearing animals decreased, but the difference was significant only in the group treated with the low dose of NNN in combination with BLE. However, in all the BLE treated animals, irrespective of the dose of nitrosamine, the hepatic vitamin A and C levels were elevated significantly as compared to the corresponding nitrosamine-treated controls. These results indicate that BLE has a promising anticarcinogenic role to play in tobacco induced cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Feasibility of preventing the effects of carcinogens on man

    Energy Technology Data Exchange (ETDEWEB)

    Shabad, L M; Wittig, K; Khesina, I A

    1973-01-01

    Measures are considered for reducing atmospheric levels of polycyclic aromatic hydrocarbons produced by domestic heating, industry, and motor vehicles. Older home heating systems should be replaced with ones which can burn more efficiently. It is recommended that emissions from industrial sources, such as by-product coke plants, petroleum refineries, and plants producing carbon black, resins, and gas, should be reduced by the use of filters or by more complete combustion. The amount of polycyclic aromatic hydrocarbons in motor vehicle exhaust can be reduced by using oil additives, changing the ratio of gasoline to oil, and using neutralizers, but more appropriate long-term solutions would be to use vehicles powered by gas or electricity. Since the largest amounts of benzyprene (BP) are produced by idling motors, traffic flow should be improved by separating foot and automobile traffic. The amount of BP in airplane emissions has been reduced by more than 30% by adding magnesium to the fuel and by about 60% by using dearomatized fuels. To prevent lung cancer it is necessary to reduce the levels of not only carcinogens and cocarcinogens, but also of toxic substances, e.g., sulfur dioxide, oxides of nitrogen, and acrolein, which reduce ciliary activity in the bronchial epithelium. Since it is impractical to eliminate polycyclic aromatic hydrocarbons from the human environment at present, maximum permissible concentrations of BP have been established in the Soviet Union. They are 0.01 microg/100 m/sup 3/ BP for the atmosphere and 15 microg/100 m/sup 3/ in work places.

  2. Seismic shear wall ISP NUPEC's seismic ultimate dynamic response test. Comparison report

    International Nuclear Information System (INIS)

    1996-01-01

    In the seismic design of a nuclear power plant, evaluation of the ultimate strength of the nuclear reactor building is an important subject for assessment of seismic reliability of the plant. In order to carry out the evaluation, the response characteristics of reinforced concrete seismic shear walls up to their ultimate state have to be understood. For this purpose, there is a need to develop reliable non-linear response analysis methods which enables the reliable ultimate strength evaluation of nuclear reactor buildings. Along with this need, many computer codes have been developed. These computer codes are compared. (K.A.)

  3. Effect of DNA type on response of DNA biosensor for carcinogens

    Science.gov (United States)

    Sani, Nor Diyana bt. Md.; Heng, Lee Yook; Surif, Salmijah; Lazim, Azwani Mat

    2013-11-01

    Carcinogens are cancer causing chemicals that can bind to DNA and cause damage to the DNA. These chemicals are available everywhere including in water, air, soil and food. Therefore, a sensor that can detect the presence of these chemicals will be a very useful tool. Since carcinogens bind to DNA, DNA can be used as the biological element in a biosensor. This study has utilized different types of DNA in a biosensor for carcinogen detection. The DNAs include double stranded calf thymus DNA, single stranded calf thymus DNA and guanine rich single stranded DNA. The modified SPE was exposed to a carcinogen followed by interaction with methylene blue which acts as the electroactive indicator. The SPE was then analysed using differential pulse voltammetry (DPV). Optimization studies were conducted for MB concentration and accumulation time, DNA concentration, as well as effect of buffer concentration, buffer pH and ionic strength. The performance of the biosensor was tested on a group 1 carcinogen, formaldehyde. The results indicated that the usage of guanine rich single stranded DNA also gives higher response as carcinogens prefer to bind with guanine compared to other bases.

  4. Carcinogen susceptibility is regulated by genome architecture and predicts cancer mutagenesis.

    Science.gov (United States)

    García-Nieto, Pablo E; Schwartz, Erin K; King, Devin A; Paulsen, Jonas; Collas, Philippe; Herrera, Rafael E; Morrison, Ashby J

    2017-10-02

    The development of many sporadic cancers is directly initiated by carcinogen exposure. Carcinogens induce malignancies by creating DNA lesions (i.e., adducts) that can result in mutations if left unrepaired. Despite this knowledge, there has been remarkably little investigation into the regulation of susceptibility to acquire DNA lesions. In this study, we present the first quantitative human genome-wide map of DNA lesions induced by ultraviolet (UV) radiation, the ubiquitous carcinogen in sunlight that causes skin cancer. Remarkably, the pattern of carcinogen susceptibility across the genome of primary cells significantly reflects mutation frequency in malignant melanoma. Surprisingly, DNase-accessible euchromatin is protected from UV, while lamina-associated heterochromatin at the nuclear periphery is vulnerable. Many cancer driver genes have an intrinsic increase in carcinogen susceptibility, including the BRAF oncogene that has the highest mutation frequency in melanoma. These findings provide a genome-wide snapshot of DNA injuries at the earliest stage of carcinogenesis. Furthermore, they identify carcinogen susceptibility as an origin of genome instability that is regulated by nuclear architecture and mirrors mutagenesis in cancer. © 2017 The Authors.

  5. Correcting ligands, metabolites, and pathways

    Directory of Open Access Journals (Sweden)

    Vriend Gert

    2006-11-01

    Full Text Available Abstract Background A wide range of research areas in bioinformatics, molecular biology and medicinal chemistry require precise chemical structure information about molecules and reactions, e.g. drug design, ligand docking, metabolic network reconstruction, and systems biology. Most available databases, however, treat chemical structures more as illustrations than as a datafield in its own right. Lack of chemical accuracy impedes progress in the areas mentioned above. We present a database of metabolites called BioMeta that augments the existing pathway databases by explicitly assessing the validity, correctness, and completeness of chemical structure and reaction information. Description The main bulk of the data in BioMeta were obtained from the KEGG Ligand database. We developed a tool for chemical structure validation which assesses the chemical validity and stereochemical completeness of a molecule description. The validation tool was used to examine the compounds in BioMeta, showing that a relatively small number of compounds had an incorrect constitution (connectivity only, not considering stereochemistry and that a considerable number (about one third had incomplete or even incorrect stereochemistry. We made a large effort to correct the errors and to complete the structural descriptions. A total of 1468 structures were corrected and/or completed. We also established the reaction balance of the reactions in BioMeta and corrected 55% of the unbalanced (stoichiometrically incorrect reactions in an automatic procedure. The BioMeta database was implemented in PostgreSQL and provided with a web-based interface. Conclusion We demonstrate that the validation of metabolite structures and reactions is a feasible and worthwhile undertaking, and that the validation results can be used to trigger corrections and improvements to BioMeta, our metabolite database. BioMeta provides some tools for rational drug design, reaction searches, and

  6. Ultimate Bound of a 3D Chaotic System and Its Application in Chaos Synchronization

    Directory of Open Access Journals (Sweden)

    Jiezhi Wang

    2014-01-01

    Full Text Available Two ellipsoidal ultimate boundary regions of a special three-dimensional (3D chaotic system are proposed. To this chaotic system, the linear coefficient of the ith state variable in the ith state equation has the same sign; it also has two one-order terms and one quadratic cross-product term in each equation. A numerical solution and an analytical expression of the ultimate bounds are received. To get the analytical expression of the ultimate boundary region, a new result of one maximum optimization question is proved. The corresponding ultimate boundary regions are demonstrated through numerical simulations. Utilizing the bounds obtained, a linear controller is proposed to achieve the complete chaos synchronization. Numerical simulation exhibits the feasibility of the designed scheme.

  7. LRFD software for design and actual ultimate capacity of confined rectangular columns.

    Science.gov (United States)

    2013-04-01

    The analysis of concrete columns using unconfined concrete models is a well established practice. On the : other hand, prediction of the actual ultimate capacity of confined concrete columns requires specialized nonlinear : analysis. Modern codes and...

  8. [Deniss Hanovs, Valdis Tēraudkalns: Ultimate Freedom - no choice] / Olaf Mertelsmann

    Index Scriptorium Estoniae

    Mertelsmann, Olaf, 1969-

    2014-01-01

    Arvustus: Deniss Hanovs, Valdis Tēraudkalns: Ultimate Freedom - no choice. The culture of authoritarianism in Latvia, 1934-1940. (Central and Eastern Europe. Reginal perspectives in global context, Bd. 2.) Brill. Leiden-Boston 2013

  9. Reduced design load basis for ultimate blade loads estimation in multidisciplinary design optimization frameworks

    DEFF Research Database (Denmark)

    Pavese, Christian; Tibaldi, Carlo; Larsen, Torben J.

    2016-01-01

    The aim is to provide a fast and reliable approach to estimate ultimate blade loads for a multidisciplinary design optimization (MDO) framework. For blade design purposes, the standards require a large amount of computationally expensive simulations, which cannot be efficiently run each cost...... function evaluation of an MDO process. This work describes a method that allows integrating the calculation of the blade load envelopes inside an MDO loop. Ultimate blade load envelopes are calculated for a baseline design and a design obtained after an iteration of an MDO. These envelopes are computed...... for a full standard design load basis (DLB) and a deterministic reduced DLB. Ultimate loads extracted from the two DLBs with the two blade designs each are compared and analyzed. Although the reduced DLB supplies ultimate loads of different magnitude, the shape of the estimated envelopes are similar...

  10. Carcinogenicity study of 3-monochloropropane-1, 2-diol (3-MCPD) administered by drinking water to B6C3F1 mice showed no carcinogenic potential.

    Science.gov (United States)

    Jeong, Jayoung; Han, Beom Seok; Cho, Wan-Seob; Choi, Mina; Ha, Chang-Su; Lee, Byoung-Seok; Kim, Yong-Bum; Son, Woo-Chan; Kim, Choong-Yong

    2010-09-01

    3-Monochloropropane-1, 2-diol (or 3-chloro-1,2-propanediol, 3-MCPD) is a well-known food processing contaminant found in a wide range of foods and ingredients. It has been classified as non-genotoxic carcinogen but its carcinogenic potential in the rodents has been controversial. The carcinogenicity to B6C3F1 mice by drinking water administration was assessed over a period of 104 weeks. Three groups, each comprising 50 male and 50 female mice received 3-MCPD at dosages of 30, 100 or 300 ppm up to Day 100 and 200 ppm onward (4.2, 14.3 and 33.0 mg/kg for males; 3.7, 12.2, and 31.0 mg/kg for females), were allocated. Survival was good, with at least 80% of males and 72% of females in each group surviving 104 weeks. Body weights and body weight gain were decreased in males and females receiving 200 ppm. Water and food consumptions of both sexes at 300/200 ppm were lowered. Emaciated or crouching position was observed for animals of both sexes exposed to 200 ppm. There were some differences in hematology and serum biochemistry compared with controls, although there was no histopathological evidence to support those changes. Histopathological examination did not reveal any neoplastic or non-neoplastic findings attributable to treatment with 3-MCPD. It is concluded that drinking water administration of 3-MCPD for 104 weeks revealed no evidence of carcinogenic potential.

  11. Comparative statistical analysis of carcinogenic and non-carcinogenic effects of uranium in groundwater samples from different regions of Punjab, India

    International Nuclear Information System (INIS)

    Saini, Komal; Singh, Parminder; Bajwa, Bikramjit Singh

    2016-01-01

    LED flourimeter has been used for microanalysis of uranium concentration in groundwater samples collected from six districts of South West (SW), West (W) and North East (NE) Punjab, India. Average value of uranium content in water samples of SW Punjab is observed to be higher than WHO, USEPA recommended safe limit of 30 µg l −1 as well as AERB proposed limit of 60 µg l −1 . Whereas, for W and NE region of Punjab, average level of uranium concentration was within AERB recommended limit of 60 µg l −1 . Average value observed in SW Punjab is around 3–4 times the value observed in W Punjab, whereas its value is more than 17 times the average value observed in NE region of Punjab. Statistical analysis of carcinogenic as well as non carcinogenic risks due to uranium have been evaluated for each studied district. - Highlights: • Uranium level in groundwater samples have been assessed in different regions of Punjab. • Comparative study of carcinogenic and non carcinogenic effects of uranium has been done. • Wide variation has been found for different geological regions. • It has been found that South west Punjab is worst affected by uranium contamination in its water. • For west and north east regions of Punjab, uranium levels in groundwater laid under recommended safe limits.

  12. Hydroquinone, a benzene metabolite, induces Hog1-dependent stress response signaling and causes aneuploidy in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Shiga, Takeki; Suzuki, Hiroyuki; Yamamoto, Hiroaki; Yamamoto, Kazuo; Yamamoto, Ayumi

    2010-01-01

    Previously, we have shown that phenyl hydroquinone, a hepatic metabolite of the Ames test-negative carcinogen o-phenylphenol, efficiently induced aneuploidy in Saccharomyces cerevisiae by arresting the cell cycle at the G2/M transition as a result of the activation of the Hog1 (p38 MAPK homolog)-Swe1 (Wee1 homolog) pathway. In this experiment, we examined the aneuploidy forming effects of hydroquinone, a benzene metabolite, since both phenyl hydroquinone and hydroquinone are Ames-test negative carcinogens and share similar molecular structures. As was seen in phenyl hydroquinone, hydroquinone induced aneuploidy in yeast by delaying the cell cycle at the G2/M transition. Deficiencies in SWE1 and HOG1 abolished the hydroquinone-induced delay at the G2/M transition and aneuploidy formation. Furthermore, Hog1 was phosphorylated by hydroquinone, which may stabilize Swe1. These data indicate that the hydroquinone-induced G2/M transition checkpoint, which is activated by the Hog1-Swe1 pathway, plays a role in the formation of aneuploidy. (author)

  13. Antimycobacterial Metabolites from Marine Invertebrates.

    Science.gov (United States)

    Daletos, Georgios; Ancheeva, Elena; Chaidir, Chaidir; Kalscheuer, Rainer; Proksch, Peter

    2016-10-01

    Marine organisms play an important role in natural product-based drug research due to accumulation of structurally unique and bioactive metabolites. The exploration of marine-derived compounds may significantly extend the scientific knowledge of potential scaffolds for antibiotic drug discovery. Development of novel antitubercular agents is especially significant as the emergence of drug-resistant Mycobacterium tuberculosis strains remains threateningly high. Marine invertebrates (i.e., sponges, corals, gorgonians) as a source of new chemical entities are the center of research for several scientific groups, and the wide spectrum of biological activities of marine-derived compounds encourages scientists to carry out investigations in the field of antibiotic research, including tuberculosis treatment. The present review covers published data on antitubercular natural products from marine invertebrates grouped according to their biogenetic origin. Studies on the structure-activity relationships of these important leads are highlighted as well. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. The secondary metabolite bioinformatics portal

    DEFF Research Database (Denmark)

    Weber, Tilmann; Kim, Hyun Uk

    2016-01-01

    . In this context, this review gives a summary of tools and databases that currently are available to mine, identify and characterize natural product biosynthesis pathways and their producers based on ‘omics data. A web portal called Secondary Metabolite Bioinformatics Portal (SMBP at http...... analytical and chemical methods gave access to this group of compounds, nowadays genomics-based methods offer complementary approaches to find, identify and characterize such molecules. This paradigm shift also resulted in a high demand for computational tools to assist researchers in their daily work......Natural products are among the most important sources of lead molecules for drug discovery. With the development of affordable whole-genome sequencing technologies and other ‘omics tools, the field of natural products research is currently undergoing a shift in paradigms. While, for decades, mainly...

  15. Recommendation for basis for decision on a Danish ultimate storage for low and intermediate radioactive wastes

    International Nuclear Information System (INIS)

    2006-12-01

    In 2003 the Danish Parliament consented to let the government start the preparation of a basis for decision on a Danish ultimate storage for low and intermediate radioactive wastes. The present report is the result of the preparation process, and it describes the fundamental safety and environmental principles for establishing an ultimate storage, including determining the principles for the site selection, storage construction, and safety analyses. (LN)

  16. A Technique for Temperature and Ultimate Load Calculations of Thin Targets in a Pulsed Electron Beam

    DEFF Research Database (Denmark)

    Hansen, Jørgen-Walther; Lundsager, Per

    1979-01-01

    A technique is presented for the calculation of transient temperature distributions and ultimate load of rotationally symmetric thin membranes with uniform lateral load and exposed to a pulsed electron beam from a linear accelerator. Heat transfer by conduction is considered the only transfer...... mechanism. The ultimate load is calculated on the basis of large plastic strain analysis. Analysis of one aluminum and one titanium membrane is shown....

  17. Use of the modified Ames test as an indicator of the carcinogenicity of residual aromatic extracts

    Energy Technology Data Exchange (ETDEWEB)

    Boogaard, P.; Hedelin, A.; Riley, A.; Rushton, E.; Vaissiere, M.; Minsavage, G.; Rohde, A.; Dalbey, W.

    2013-01-15

    Existing data demonstrate that residual aromatic extracts (RAEs) can be either carcinogenic or non-carcinogenic. CONCAWE had previously concluded that 'Although limited data available indicate that some RAEs are weakly carcinogenic, it is not possible to provide a general recommendation. Classify on a case-by-case basis' (CONCAWE 2005). Therefore CONCAWE's Health/Toxicology Subgroup (H/TSG) has developed a proposal for the use of the modified Ames test as a short-term predictive screening tool for decisions on the classification of RAEs for carcinogenicity. The relationship between RAE chemistry and carcinogenic potential is not as well understood as it is for some other categories of substances, e.g. Other Lubricant Base Oils (OLBO). However, a correlation has been found between the results of the skin carcinogenicity bioassay and the mutagenicity index (MI) obtained from the modified Ames test. Data supporting this correlation are summarised in this report. The H/TSG confirmed that the modified Ames test can be used as a predictive screening tool and that a cut-off value can be established to make a distinction between carcinogenic and non-carcinogenic products. RAEs with a MI > 0.4 demonstrated carcinogenic potential upon dermal application to mouse skin with chronic exposure. RAEs with a MI > 0.4 did not demonstrate a carcinogenic potential. To justify the use of the modified Ames test with RAEs, additional analysis of the repeatability of the test with RAEs was required. With this objective, CONCAWE sponsored a round robin study with different samples of RAEs from member companies, at three different laboratories. The repeatability demonstrated in the round robin study with RAEs support the proposed use of the modified Ames test. As part of the tools available for use by member companies, the H/TSG proposed a standard operating procedure (SOP) (included as an Appendix to this report) on the conduct of the modified Ames test with RAEs. The H

  18. Microsomal metabolism of trenbolone acetate metabolites ...

    Science.gov (United States)

    Trenbolone acetate (TBA) is a synthetic growth promoter widely used in animal agriculture, and its metabolites are suspected endocrine disrupting compounds in agriculturally impacted receiving waters. However, beyond the three widely recognized TBA metabolites (17-trenbolone, 17-trenbolone and trendione), little is known about other metabolites formed in vivo and subsequently discharged into the environment, with some evidence suggesting these unknown metabolites comprise a majority of the TBA mass dosed to the animal. Here, we explored the metabolism of the three known TBA metabolites using rat liver microsome studies. All TBA metabolites are transformed into a complex mixture of monohydroxylated products. Based on product characterization, the majority are more polar than the parent metabolites but maintain their characteristic trienone backbone. A minor degree of interconversion between known metabolites was also observed, as were higher order hydroxylated products with a greater extent of reaction. Notably, the distribution and yield of products were generally comparable across a series of variably induced rat liver microsomes, as well as during additional studies with human and bovine liver microsomes. Bioassays conducted with mixtures of these transformation products suggest that androgen receptor (AR) binding activity is diminished as a result of the microsomal treatment, suggesting that the transformation products are generally less potent than

  19. SECONDARY METABOLITES FROM MARINE PENICILLIUM BREVICOMPACTUM

    OpenAIRE

    ROVIROSA, JUANA; DIAZ-MARRERO, ANA; DARIAS, JOSE; PAINEMAL, KARIN; SAN MARTIN, AURELIO

    2006-01-01

    In a screening of Basidiomycete cultures isolated from marine invertebrates collected along the Chilean coastline for the production of antibiotics we identified a Penicillium brevicompactum strain as a producer of metabolites inhibiting the growth of bacteria and fungi. Bioactivity guided purification resulted in the isolation of four known metabolites. Their structures were elucidated by spectroscopic methods.

  20. Biochemical and secondary metabolites changes under moisture ...

    African Journals Online (AJOL)

    The study showed the importance of carbohydrate and nitrogen cycle related metabolites in mediating tolerance in cassava by affecting their phenotypic expression in the plant. Keywords: Hydrothermal stress, bio-chemicals, pigments, secondary metabolites, cassava. African Journal of Biotechnology, Vol 13(31) 3173-3186 ...

  1. MARSI: metabolite analogues for rational strain improvement

    DEFF Research Database (Denmark)

    Cardoso, João G. R.; Zeidan, Ahmad A; Jensen, Kristian

    2018-01-01

    reactions in an organism can be used to predict effects of MAs on cellular phenotypes. Here, we present the Metabolite Analogues for Rational Strain Improvement (MARSI) framework. MARSI provides a rational approach to strain improvement by searching for metabolites as targets instead of genes or reactions...

  2. Educational attainment and ultimate fertility among Swedish women born in 1955-59

    Directory of Open Access Journals (Sweden)

    Gerda Neyer

    2006-05-01

    Full Text Available This is the second of two companion papers addressing the association between educational attainment and fertility for some sixty educational groups of Swedish women, defined according to field of education as well as level of education. The first paper is about childlessness and education, the present one about the mean number of children ever born. We find that ultimate fertility decreases somewhat with an increasing educational level, but its dependence on the field of education is much more impressive. In general, educational groups with relatively little childlessness also have relatively high ultimate fertility, and educational groups with much childlessness have relatively low ultimate fertility. In particular, women educated for the teaching or health-care professions have less childlessness and a higher ultimate fertility than others. Conversely, women with an education for esthetic or (non-teacher humanist occupations have unusually high fractions childless and low ultimate fertility. Women with religious educations stand out by having very high fractions childless but quite ordinary mean ultimate fertility nevertheless; such women have very little childbearing outside of marriage. Women with research degrees have remarkably ordinary childbearing behavior; they do not forego motherhood to the extent that some theories would predict.

  3. Excess glycogen does not resolve high ultimate pH of oxidative muscle.

    Science.gov (United States)

    England, Eric M; Matarneh, Sulaiman K; Oliver, Emily M; Apaoblaza, Ariel; Scheffler, Tracy L; Shi, Hao; Gerrard, David E

    2016-04-01

    Skeletal muscle glycogen content can impact the extent of postmortem pH decline. Compared to glycolytic muscles, oxidative muscles contain lower glycogen levels antemortem which may contribute to the higher ultimate pH. In an effort to explore further the participation of glycogen in postmortem metabolism, we postulated that increasing the availability of glycogen would drive additional pH decline in oxidative muscles to equivalent pH values similar to the ultimate pH of glycolytic muscles. Glycolysis and pH declines were compared in porcine longissimus lumborum (glycolytic) and masseter (oxidative) muscles using an in vitro system in the presence of excess glycogen. The ultimate pH of the system containing longissimus lumborum reached a value similar to that observed in intact muscle. The pH decline of the system containing masseter samples stopped prematurely resulting in a higher ultimate pH which was similar to that of intact masseter muscle. To investigate further, we titrated powdered longissimus lumborum and masseter samples in the reaction buffer. As the percentage of glycolytic sample increased, the ultimate pH decreased. These data show that oxidative muscle produces meat with a high ultimate pH regardless of glycogen content and suggest that inherent muscle factors associated with glycolytic muscle control the extent of pH decline in pig muscles. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Assessment on Ultimate Load of Cold-formed Steel Channel (CFSC Stub Column

    Directory of Open Access Journals (Sweden)

    Mohd Sani Mohd Syahrul Hisyam

    2015-01-01

    Full Text Available Cold-formed steel is used as the non-structural and structural material in civil engineering work and building. Cold-formed steel channel is selected and cut into 100 mm, 200 mm, 300 mm, 400 mm and 500 mm. The slenderness ratio is calculated and noted as a stub or short column because below 40. The column is tested by using Universal Testing Machine to determine the ultimate load of the stub column. Besides, the CFSC is determined the material properties of CFSC for checking it’s the originality of steel based material. The experimental data are tested and compared with the Direct Strength Method (DSM. It showed that the CFSC1 with a height of 100 mm is reported to have a higher value of ultimate load when compared with other samples. When the height of the stub column increased, the ultimate load of the sample is decreased. Then, the CFSC1 also showed a higher in initial stiffness when compared with other samples. All samples are shown having a higher data in ultimate load when compared with the Direct Strength Method prediction. The ultimate load of experimental and DSM all gave a ratio below 1.03. Finally, all samples can further recommend determining the relation between the ultimate loads with variations of height of the column.

  5. Complicating factors in safety testing of drug metabolites: Kinetic differences between generated and preformed metabolites

    International Nuclear Information System (INIS)

    Prueksaritanont, Thomayant; Lin, Jiunn H.; Baillie, Thomas A.

    2006-01-01

    This paper aims to provide a scientifically based perspective on issues surrounding the proposed toxicology testing of synthetic drug metabolites as a means of ensuring adequate nonclinical safety evaluation of drug candidates that generate metabolites considered either to be unique to humans or are present at much higher levels in humans than in preclinical species. We put forward a number of theoretical considerations and present several specific examples where the kinetic behavior of a preformed metabolite given to animals or humans differs from that of the corresponding metabolite generated endogenously from its parent. The potential ramifications of this phenomenon are that the results of toxicity testing of the preformed metabolite may be misleading and fail to characterize the true toxicological contribution of the metabolite when formed from the parent. It is anticipated that such complications would be evident in situations where (a) differences exist in the accumulation of the preformed versus generated metabolites in specific tissues, and (b) the metabolite undergoes sequential metabolism to a downstream product that is toxic, leading to differences in tissue-specific toxicity. Owing to the complex nature of this subject, there is a need to treat drug metabolite issues in safety assessment on a case-by-case basis, in which a knowledge of metabolite kinetics is employed to validate experimental paradigms that entail administration of preformed metabolites to animal models

  6. A new paradigm for known metabolite identification in metabonomics/metabolomics: metabolite identification efficiency.

    Science.gov (United States)

    Everett, Jeremy R

    2015-01-01

    A new paradigm is proposed for assessing confidence in the identification of known metabolites in metabonomics studies using NMR spectroscopy approaches. This new paradigm is based upon the analysis of the amount of metabolite identification information retrieved from NMR spectra relative to the molecular size of the metabolite. Several new indices are proposed including: metabolite identification efficiency (MIE) and metabolite identification carbon efficiency (MICE), both of which can be easily calculated. These indices, together with some guidelines, can be used to provide a better indication of known metabolite identification confidence in metabonomics studies than existing methods. Since known metabolite identification in untargeted metabonomics studies is one of the key bottlenecks facing the science currently, it is hoped that these concepts based on molecular spectroscopic informatics, will find utility in the field.

  7. A New Paradigm for Known Metabolite Identification in Metabonomics/Metabolomics: Metabolite Identification Efficiency

    Directory of Open Access Journals (Sweden)

    Jeremy R. Everett

    2015-01-01

    Full Text Available A new paradigm is proposed for assessing confidence in the identification of known metabolites in metabonomics studies using NMR spectroscopy approaches. This new paradigm is based upon the analysis of the amount of metabolite identification information retrieved from NMR spectra relative to the molecular size of the metabolite. Several new indices are proposed including: metabolite identification efficiency (MIE and metabolite identification carbon efficiency (MICE, both of which can be easily calculated. These indices, together with some guidelines, can be used to provide a better indication of known metabolite identification confidence in metabonomics studies than existing methods. Since known metabolite identification in untargeted metabonomics studies is one of the key bottlenecks facing the science currently, it is hoped that these concepts based on molecular spectroscopic informatics, will find utility in the field.

  8. The carcinogenic effects of aspartame: The urgent need for regulatory re-evaluation.

    Science.gov (United States)

    Soffritti, Morando; Padovani, Michela; Tibaldi, Eva; Falcioni, Laura; Manservisi, Fabiana; Belpoggi, Fiorella

    2014-04-01

    Aspartame (APM) is an artificial sweetener used since the 1980s, now present in >6,000 products, including over 500 pharmaceuticals. Since its discovery in 1965, and its first approval by the US Food and Drugs Administration (FDA) in 1981, the safety of APM, and in particular its carcinogenicity potential, has been controversial. The present commentary reviews the adequacy of the design and conduct of carcinogenicity bioassays on rodents submitted by G.D. Searle, in the 1970s, to the FDA for market approval. We also review how experimental and epidemiological data on the carcinogenic risks of APM, that became available in 2005 motivated the European Commission (EC) to call the European Food and Safety Authority (EFSA) for urgent re-examination of the available scientific documentation (including the Searle studies). The EC has further requested that, if the results of the evaluation should suggest carcinogenicity, major changes must be made to the current APM specific regulations. Taken together, the studies performed by G.D. Searle in the 1970s and other chronic bioassays do not provide adequate scientific support for APM safety. In contrast, recent results of life-span carcinogenicity bioassays on rats and mice published in peer-reviewed journals, and a prospective epidemiological study, provide consistent evidence of APM's carcinogenic potential. On the basis of the evidence of the potential carcinogenic effects of APM herein reported, a re-evaluation of the current position of international regulatory agencies must be considered an urgent matter of public health. © 2014 Wiley Periodicals, Inc.

  9. Development of quantitative structure-activity relationship (QSAR) models to predict the carcinogenic potency of chemicals

    International Nuclear Information System (INIS)

    Venkatapathy, Raghuraman; Wang Chingyi; Bruce, Robert Mark; Moudgal, Chandrika

    2009-01-01

    Determining the carcinogenicity and carcinogenic potency of new chemicals is both a labor-intensive and time-consuming process. In order to expedite the screening process, there is a need to identify alternative toxicity measures that may be used as surrogates for carcinogenic potency. Alternative toxicity measures for carcinogenic potency currently being used in the literature include lethal dose (dose that kills 50% of a study population [LD 50 ]), lowest-observed-adverse-effect-level (LOAEL) and maximum tolerated dose (MTD). The purpose of this study was to investigate the correlation between tumor dose (TD 50 ) and three alternative toxicity measures as an estimator of carcinogenic potency. A second aim of this study was to develop a Classification and Regression Tree (CART) between TD 50 and estimated/experimental predictor variables to predict the carcinogenic potency of new chemicals. Rat TD 50 s of 590 structurally diverse chemicals were obtained from the Cancer Potency Database, and the three alternative toxicity measures considered in this study were estimated using TOPKAT, a toxicity estimation software. Though poor correlations were obtained between carcinogenic potency and the three alternative toxicity (both experimental and TOPKAT) measures for the CPDB chemicals, a CART developed using experimental data with no missing values as predictor variables provided reasonable estimates of TD 50 for nine chemicals that were part of an external validation set. However, if experimental values for the three alternative measures, mutagenicity and logP are not available in the literature, then either the CART developed using missing experimental values or estimated values may be used for making a prediction

  10. Detection of genotoxic and non-genotoxic carcinogens in Xpc−/−p53+/− mice

    International Nuclear Information System (INIS)

    Melis, Joost P.M.; Speksnijder, Ewoud N.; Kuiper, Raoul V.; Salvatori, Daniela C.F.; Schaap, Mirjam M.; Maas, Saskia; Robinson, Joke; Verhoef, Aart; Benthem, Jan van; Luijten, Mirjam; Steeg, Harry van

    2013-01-01

    An accurate assessment of the carcinogenic potential of chemicals and pharmaceutical drugs is essential to protect humans and the environment. Therefore, substances are extensively tested before they are marketed to the public. Currently, the rodent two-year bioassay is still routinely used to assess the carcinogenic potential of substances. However, over time it has become clear that this assay yields false positive results and also has several economic and ethical drawbacks including the use of large numbers of animals, the long duration, and the high cost. The need for a suitable alternative assay is therefore high. Previously, we have proposed the Xpa*p53 mouse model as a very suitable alternative to the two-year bioassay. We now show that the Xpc*p53 mouse model preserves all the beneficial traits of the Xpa*p53 model for sub-chronic carcinogen identification and can identify both genotoxic and non-genotoxic carcinogens. Moreover, Xpc*p53 mice appear to be more responsive than Xpa*p53 mice towards several genotoxic and non-genotoxic carcinogens. Furthermore, Xpc*p53 mice are far less sensitive than Xpa*p53 mice for the toxic activity of DNA damaging agents and as such clearly respond in a similar way as wild type mice do. These advantageous traits of the Xpc*p53 model make it a better alternative for in vivo carcinogen testing than Xpa*p53. This pilot study suggests that Xpc*p53 mice are suited for routine sub-chronic testing of both genotoxic and non-genotoxic carcinogens and as such represent a suitable alternative to possibly replace the murine life time cancer bioassay. Highlights: ► The Xpc*p53 mouse model is able to identify genotoxic and non-genotoxic carcinogens. ► Time, animals and cost can be significantly reduced compared to the 2-year bioassay. ► Xpc*p53 mice are more advantageous for carcinogen identification than Xpa*p53 mice. ► Xpc*p53 mice exhibit a wild type response upon exposure to genotoxicants.

  11. Non-genotoxic carcinogens: early effects on gap junctions, cell proliferation and apoptosis in the rat

    International Nuclear Information System (INIS)

    Mally, Angela; Chipman, James Kevin

    2002-01-01

    Non-genotoxic carcinogens are thought to induce tumour formation by disturbing the balance between cell growth and cell death. Gap junctions (GJ) contribute to the maintenance of tissue homeostasis by allowing the intercellular exchange of growth regulatory signals and potential inhibition of GJ intercellular communication through loss of connexin (Cx) plaques has been shown to be involved in the cancer process. We have investigated the time- and dose-dependent effects of the non-genotoxic hepatocarcinogens Wy-14,643, 2,3,7,8-tetrachlorodibenzo-p-dioxin, methapyrilene and hexachlorobenzene and the male rat kidney carcinogens chloroform, p-dichlorobenzene and d-limonene on gap junction plaque expression in relation to proliferation and apoptosis. With the exception of limonene, all non-genotoxic carcinogens significantly reduced the expression of GJ plaques containing Cx32 in their respective target tissue. No dose-dependent, significant effects were seen in non-target organs. Although alteration of Cx32 expression did not appear to correlate with induction of cell proliferation, out data suggest that the interaction of both processes--interference of GJ coupled with a proliferative stimulus (at the carcinogenic dose)--may be important in non-genotoxic carcinogenesis and provide a potential alert for non-genotoxic carcinogens in short-term toxicity tests

  12. Identifying carcinogenic activity of methylated and non-methylated polycyclic aromatic hydrocarbons (PAHs) through electronic and topological indices

    CERN Document Server

    Braga, R S; Barone, P M V B

    2000-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are a class of planar molecules, abundant in urban environment, which can induce chemical carcinogenesis. Their carcinogenic power varies in a large range, from very strong carcinogens to inactive ones. In a previous study, we proposed a methodology to identify the PAHs carcinogenic activity exploring electronic and topological indices. In the present work, we show that it is possible to simplify that methodology and expand its applicability to include methylated PAHs compounds. Using very simple rules, we can predict their carcinogenic activity with high accuracy (approx 89%).

  13. Dynamic Metabolite Profiling in an Archaeon Connects Transcriptional Regulation to Metabolic Consequences.

    Directory of Open Access Journals (Sweden)

    Horia Todor

    Full Text Available Previous work demonstrated that the TrmB transcription factor is responsible for regulating the expression of many enzyme-coding genes in the hypersaline-adapted archaeon Halobacterium salinarum via a direct interaction with a cis-regulatory sequence in their promoters. This interaction is abolished in the presence of glucose. Although much is known about the effects of TrmB at the transcriptional level, it remains unclear whether and to what extent changes in mRNA levels directly affect metabolite levels. In order to address this question, here we performed a high-resolution metabolite profiling time course during a change in nutrients using a combination of targeted and untargeted methods in wild-type and ΔtrmB strain backgrounds. We found that TrmB-mediated transcriptional changes resulted in widespread and significant changes to metabolite levels across the metabolic network. Additionally, the pattern of growth complementation using various purines suggests that the mis-regulation of gluconeogenesis in the ΔtrmB mutant strain in the absence of glucose results in low phosphoribosylpyrophosphate (PRPP levels. We confirmed these low PRPP levels using a quantitative mass spectrometric technique and found that they are associated with a metabolic block in de novo purine synthesis, which is partially responsible for the growth defect of the ΔtrmB mutant strain in the absence of glucose. In conclusion, we show how transcriptional regulation of metabolism affects metabolite levels and ultimately, phenotypes.

  14. Dynamic Metabolite Profiling in an Archaeon Connects Transcriptional Regulation to Metabolic Consequences.

    Science.gov (United States)

    Todor, Horia; Gooding, Jessica; Ilkayeva, Olga R; Schmid, Amy K

    2015-01-01

    Previous work demonstrated that the TrmB transcription factor is responsible for regulating the expression of many enzyme-coding genes in the hypersaline-adapted archaeon Halobacterium salinarum via a direct interaction with a cis-regulatory sequence in their promoters. This interaction is abolished in the presence of glucose. Although much is known about the effects of TrmB at the transcriptional level, it remains unclear whether and to what extent changes in mRNA levels directly affect metabolite levels. In order to address this question, here we performed a high-resolution metabolite profiling time course during a change in nutrients using a combination of targeted and untargeted methods in wild-type and ΔtrmB strain backgrounds. We found that TrmB-mediated transcriptional changes resulted in widespread and significant changes to metabolite levels across the metabolic network. Additionally, the pattern of growth complementation using various purines suggests that the mis-regulation of gluconeogenesis in the ΔtrmB mutant strain in the absence of glucose results in low phosphoribosylpyrophosphate (PRPP) levels. We confirmed these low PRPP levels using a quantitative mass spectrometric technique and found that they are associated with a metabolic block in de novo purine synthesis, which is partially responsible for the growth defect of the ΔtrmB mutant strain in the absence of glucose. In conclusion, we show how transcriptional regulation of metabolism affects metabolite levels and ultimately, phenotypes.

  15. Focused Metabolite Profiling for Dissecting Cellular and Molecular Processes of Living Organisms in Space Environments

    Science.gov (United States)

    2008-01-01

    Regulatory control in biological systems is exerted at all levels within the central dogma of biology. Metabolites are the end products of all cellular regulatory processes and reflect the ultimate outcome of potential changes suggested by genomics and proteomics caused by an environmental stimulus or genetic modification. Following on the heels of genomics, transcriptomics, and proteomics, metabolomics has become an inevitable part of complete-system biology because none of the lower "-omics" alone provide direct information about how changes in mRNA or protein are coupled to changes in biological function. The challenges are much greater than those encountered in genomics because of the greater number of metabolites and the greater diversity of their chemical structures and properties. To meet these challenges, much developmental work is needed, including (1) methodologies for unbiased extraction of metabolites and subsequent quantification, (2) algorithms for systematic identification of metabolites, (3) expertise and competency in handling a large amount of information (data set), and (4) integration of metabolomics with other "omics" and data mining (implication of the information). This article reviews the project accomplishments.

  16. Ultimate dynamics of the Kirschner-Panetta model: Tumor eradication and related problems

    Science.gov (United States)

    Starkov, Konstantin E.; Krishchenko, Alexander P.

    2017-10-01

    In this paper we consider the ultimate dynamics of the Kirschner-Panetta model which was created for studying the immune response to tumors under special types of immunotherapy. New ultimate upper bounds for compact invariant sets of this model are given, as well as sufficient conditions for the existence of a positively invariant polytope. We establish three types of conditions for the nonexistence of compact invariant sets in the domain of the tumor-cell population. Our main results are two types of conditions for global tumor elimination depending on the ratio between the proliferation rate of the immune cells and their mortality rate. These conditions are described in terms of simple algebraic inequalities imposed on model parameters and treatment parameters. Our theoretical studies of ultimate dynamics are complemented by numerical simulation results.

  17. Revisiting perceptions of quality of hospice care: managing for the ultimate referral.

    Science.gov (United States)

    Churchman, Richard; York, Grady S; Woodard, Beth; Wainright, Charles; Rau-Foster, Mary

    2014-08-01

    Hospice services provided in the final months of life are delivered through complex interpersonal relationships between caregivers, patients, and families. Often, service value and quality are defined by these interpersonal interactions. This understanding provides hospice leaders with an enormous opportunity to create processes that provide the optimal level of care during the last months of life. The authors argue that the ultimate referral is attained when a family member observes the care of a loved one, and the family member conveys a desire to receive the same quality of services their loved one received at that facility. The point of this article is to provide evidence that supports the methods to ultimately enhance the patient's and family's experience and increase the potential for the ultimate referral. © The Author(s) 2013.

  18. Ultimate Owner and Firm Performance - Evidence from Romanian Mining and Quarrying Listed Firms

    Directory of Open Access Journals (Sweden)

    Cosmin MIHAI

    2012-08-01

    Full Text Available The main objectives of this paper are to describe the necessary steps to identify the ultimate owner and to investigate the relation between the ultimate ownership and the financial performance of Romanian mining and quarrying listed firms. The study was conducted for the companies listed on Bucharest Stock Exchange, in both regulated and non-regulated segments. The final sample included 17 companies of mining and quarrying. Return on Equity was used for measuring the financial performance of the firms. The ultimate ownership was measured by the percentage of voting rights held by a shareholder. Econometric tools like multiple linear regression analysis were used for analysis. The results of the study suggest that there is a significant negative link between financial performance and divergence between voting rights and cash-flow rights.

  19. The importance of mines for ultimate storage at Deilmann-Haniel Shaft Sinking

    International Nuclear Information System (INIS)

    Greinacher, Jochen; Oellers, Thomas; Ahlbrecht, Thomas

    2011-01-01

    Deilmann-Haniel Shaft Sinking GmbH and its predecessor and associate companies have been involved in projects for underground ultimate storage in Germany, Europe and America for over 45 years. The field of activities previously comprised surveying, planning and sinking of shafts, repair and conversion work, design of underground sealing structures, planning of conveyors and support of the BfS in planning approval procedures. Following discontinuation of activities in the German coal mining industry the use of mines for ultimate storage is an important support for German specialist mining companies. The use of mines for ultimate storage ensures that the existing mining know how in Germany is maintained, because training of the younger generation on the commercial and engineering side of the companies is made possible by the imminent major projects.

  20. Identification of an unintended consequence of Nrf2-directed cytoprotection against a key tobacco carcinogen plus a counteracting chemopreventive intervention

    Science.gov (United States)

    Paonessa, Joseph D.; Ding, Yi; Randall, Kristen L.; Munday, Rex; Argoti, Dayana; Vouros, Paul; Zhang, Yuesheng

    2011-01-01

    Nrf2 is a major cytoprotective gene and is a key chemopreventive target against cancer and other diseases. Here we show that Nrf2 faces a dilemma in defense against 4-aminobiphenyl (ABP), a major human bladder carcinogen from tobacco smoke and other environmental sources. While Nrf2 protected mouse liver against ABP (which is metabolically activated in liver), the bladder level of N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP), the predominant ABP-DNA adduct formed in bladder cells and tissues, was markedly higher in Nrf2+/+ mice than in Nrf2−/− mice after ABP exposure. Notably, Nrf2 protected bladder cells against ABP in vitro. Mechanistic investigations showed that the dichotomous effects of Nrf2 could be explained at least partly by upregulation of UDP-glucuronosyltransferase (UGT). Nrf2 promoted conjugation of ABP with glucuronic acid in the liver, increasing urinary excretion of the conjugate. While glucuronidation of ABP and its metabolites is a detoxification process, these conjugates, which are excreted in urine, are known to be unstable in acidic urine, leading to delivery of the parent compounds to bladder. Hence, while higher liver UGT activity may protect the liver against ABP it increases bladder exposure to ABP. These findings raise concerns of potential bladder toxicity when Nrf2-activating chemopreventive agents are used in humans exposed to ABP, especially in smokers. We further demonstrate that 5,6-dihydrocyclopenta[c][1,2]-dithiole-3(4H)-thione (CPDT) significantly inhibits dG-C8-ABP formation in bladder cells and tissues, but does not appear to significantly modulate ABP-catalyzing UGT in liver. Thus, CPDT exemplifies a counteracting solution to the dilemma posed by Nrf2. PMID:21487034

  1. On the decrease of ultimate elongation of gum elastomer by irradiation

    International Nuclear Information System (INIS)

    Ito, Masayuki

    1986-01-01

    The reason why the ultimate elongation of gum elastomer decreases by irradiation was studied. The sample used is tetrafluoroethylenepropylene copolymer vulcanized which is a heat resistant elastomer. The sample was irradiated by a electron beam at room temperature. Cross-linking predominate in the operation. (Case 1) Scission predominant condition (Case 2) was given by irradiation of Co-60 γ ray at 100 deg C. Alternative irradiation of γ ray and electron beam under above condition can keep the original cross-linking density by the appropriate choice of each of the doses. (Case 3) The three cases mentioned above involve all of the cases of radiation induced aging of elastomers. Therefor, the following explanation for three cases shows the reason why the ultimate elongation of gum elastomer decreases by irradiation. Case 1. Cross-linking predominant condition. Ultimate elongation is proportional to -0.5 power of the dose. This fact can be explicable by the model of Buche, i.e. the breaking of a short chain causes another to break and that so on throughout the whole sample. Case 2. Chain scission predominant condition. Ultimate elongation increases by irradiation for a certain dose. This fact can understand by the model of Buche. But from a certain dose ultimate elongation does not increase. In the period the structure of the sample turned to be the same structure as the low molecular weight amorphose polymer vulcanized. Case 3. Rate of cross-linking and scission is the same. The average chain length does not chainge in the condition. But the distribution of chain length became wider and wider by irradiation. The increase of short chain result the decrease in ultimate elongation. (author)

  2. Factors modifying sensitivity to carcinogens and the problem of threshold in carcinogenesis

    International Nuclear Information System (INIS)

    Anisimov, V.N.

    1983-01-01

    Maximum allowable concentrations of chemical carcinogens and dose rates of ionizing radiation have been under extensive study both experimentally and epidemiologically. The problem of the carcinogenic hazards of low-level radiation is a very difficult one: in epidemiological studies it is hard to take into account the many factors (e.g. diseases, diet, genetic peculiarities) that may affect sensitivity to radiation; in experimental studies it is hard to extrapolate with accuracy from one species to another or from the individual threshold to that of the whole population. Age, enzyme activity, sex, and DNA repair capability also modify sensitivity to radiation; when factors such as these are better understood it is expected that epidemiological studies will give a solution that allows estimation of the carcinogenic risk from low-level radiation and hence establishment of a threshold dose. (author)

  3. Inconsistency... or why differentiate, where prevention is concerned, between radioactive substances and carcinogenic chemicals

    International Nuclear Information System (INIS)

    Choquet, R.; Vinit, J.

    1982-01-01

    Radiotracers, low-activity unsealed radioactive sources, and certain chemical products belong to the list of substances and agents known to promote cancers in humans. The dangers of radiotracers and carcinogenic chemicals being very similar, or even identical, it is inadmissible that preventive measures have not been equally developed and are not viewed in the same way in our country. It should be noted that the International Labour Bureau has long since included radioactive products in the list of carcinogenic substances and agents and treated preventive measures as a whole by proceeding in this way it would be easier to account for the possible combined effects of ionising radiations and chemical molecules. After a review of some facts about cancer the present situation is examined with regard to statutory measures applied on the one hand to radioelements and on the other to chemicals recognised as carcinogenic by international organisations. Proposals are made to remedy this illogical situation [fr

  4. [Cardiovascular risk, occupation and exposure to occupational carcinogens in a group of workers in Salamanca].

    Science.gov (United States)

    González-Sánchez, Jesús

    2015-01-01

    Identify the cardiovascular risk factors in a group of workers in the province of Salamanca, protected by external prevention services, as regards exposure to occupational carcinogens, by sector of activity and gender. An observational descriptive epidemiological study was conducted. The sample selection was by stratified random sampling in each entity. The variables collected by questionnaire were, sociodemographic characteristics, exposure to occupational carcinogens, and cardiovascular risk factors (smoking, hypertension, dyslipidemia, and diabetes), using the clinical-work histories as a source of information. Statistically significant differences were observed in cardiovascular risk according to the exposure to occupational carcinogens (p cardiovascular risk in the work place. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  5. Policy issues in setting de minimis standards for latent cancer risks of radiation and chemical carcinogens

    International Nuclear Information System (INIS)

    Spangler, M.

    1984-01-01

    In the fuel cycles for the development and utilization of alternative energy resources, the risk of latent cancer arises from a number of sources. Included are ionizing radiation and the carcinogenic potential of polluting chemicals present in certain fuels or in materials associated with the construction, operation, maintenance or waste treatment processes of nuclear power, fossil fuels, synfuels, biomass, and other sources of energy. One aspect of developing a carcinogen guideline policy for a consistent and effective regulatory regime to use in dealing with these assorted carcinogenic risks is the setting of de minimis quantitative standards. In this report, 11 policy issues related to the setting of such regulatory standards are identified and a brief commentary is provided. 15 references, 1 table

  6. The carcinogenicity of 1-methyl-3(p-bromophenyl)-1-nitrosourea (Br-MPNU).

    Science.gov (United States)

    Warzok, R; Martin, J; Mendel, J; Thust, R; Schwarz, H

    1983-01-01

    In long-term experiments with Hooded rats the carcinogenic potential of 1-methyl-3(p-bromophenyl)-1-nitrosourea (Br-MPNU) could be demonstrated for the first time. Br-MPNU is formed also endogenously after combined administration of 1-methyl-3(p-bromophenyl)-urea (Br-MPU) and sodium nitrite. After repeated intragastric administration of 0.33 mmol Br-MPU and 0.73 mmol NaNO2 per kg b.w. papillomas and carcinomas of the forestomach developed in 83%. After repeated administration of 0.28 mmol Br-MPNU per kg b.w. these neoplasms were observed in 88%. The comparison of results obtained in similar experiments with 1-methyl-3-phenyl-1-nitrosourea shows that bromine substitution led to a reduction of the carcinogenic activity. The present paper is part of a complex program studying the interrelationships between structure, physico-chemical properties, mutagenicity and carcinogenicity of nitrosoureas.

  7. Ultimate strength and ductility of steel reinforced concrete beam-columns

    International Nuclear Information System (INIS)

    Shohara, Ryoichi

    1991-01-01

    The ultimate strength and ductility of SRC beam-columns are investigated using the data gathered in Architectural Institute of Japan. Though the simple superposed strength formula in AIJ standard underestimates the strength of SRC beam-column failed in flexure, the generalized superposed strength formula estimates it satisfactory. The strength formula in AIJ standard does not good agreement with test data. The SRC beam-column failed in shear has almost equalductility with that failed in flexure owing to the encased steel. Author presents the formulas which estimate the ultimate deformation angle for SRC beam-columns. (author)

  8. Maintained ship hull girder ultimate strength reliability considering corrosion and fatigue

    DEFF Research Database (Denmark)

    Hu, Yong; Cui, W.; Pedersen, Preben Terndrup

    2004-01-01

    The prupose of this paper is to propose a methodology to assess the time-variant ultimate strength of ship hull girder under the degradations of corrosion and fatigue. The effects of fatigue cracks on the tensile and compressive residual ultimate strength of stiffened panels and unstiffened plates......, webs and flanges, respectively. The effects of inspections and repair are taken into account. A minimum net thickness rule is used to determine repair policies. A procedure is proposed to determine the maximum allowable corrosion thickness of different parts of the hull cross section. The procedure...

  9. Behaviour of concrete nuclear containment structures upto ultimate failure with special reference to MAPP-1 containment

    International Nuclear Information System (INIS)

    Appa Rao, T.V.S.R.

    1975-01-01

    Theoretical and experimental methods for investigating the behaviour of concrete secondary containment structures subjected to loads upto their ultimate failure have been discussed in the paper. Need for inelastic nonlinear analysis of containments has been emphasized. Different contitutive models of concrete that can be employed in the nonlinear analysis of concrete structures were briefly reviewed. Based on the experimental results obtained in a 1:12 scale model test conducted at the Structural Engineering Research (Regional) Centre, Madras, behaviour of the MAPP-1 containment to internal pressure loading upto its ultimate failure has been discussed. (author)

  10. Decision basis for a Danish ultimate storage for low and intermediate radioactive wastes

    International Nuclear Information System (INIS)

    2008-11-01

    In 2003 the Danish Parliament consented to let the government start the preparation of a basis for decision on a Danish ultimate storage for low and intermediate radioactive wastes. The present report was prepared by a working group and it presents the final proposal for such a decision basis. The report describes the fundamental safety and environmental principles for establishing an ultimate storage, including determining the principles for site selection, storage construction, and safety analysis. In an appendix, the amount, types, and activity level of the Danish radioactive wastes are presented. (ln)

  11. Conception of electron beam-driven subcritical molten salt ultimate safety reactor

    Energy Technology Data Exchange (ETDEWEB)

    Abalin, S.S.; Alekseev, P.N.; Ignat`ev, V.V. [Kurchatov Institute, Moscow (Russian Federation)] [and others

    1995-10-01

    This paper is a preliminary sketch of a conception to develop the {open_quotes}ultimate safety reactor{close_quotes} using modern reactor and accelerator technologies. This approach would not require a long-range R&D program. The ultimate safety reactor could produce heat and electric energy, expand the production of fuel, or be used for the transmutation of long-lived wastes. The use of the combined double molten salt reactor system allows adequate neutron multiplication to permit using an electron accelerator for the initial neutron flux. The general parameters of such a system are discussed in this paper.

  12. Comparative statistical analysis of carcinogenic and non-carcinogenic effects of uranium in groundwater samples from different regions of Punjab, India.

    Science.gov (United States)

    Saini, Komal; Singh, Parminder; Bajwa, Bikramjit Singh

    2016-12-01

    LED flourimeter has been used for microanalysis of uranium concentration in groundwater samples collected from six districts of South West (SW), West (W) and North East (NE) Punjab, India. Average value of uranium content in water samples of SW Punjab is observed to be higher than WHO, USEPA recommended safe limit of 30µgl -1 as well as AERB proposed limit of 60µgl -1 . Whereas, for W and NE region of Punjab, average level of uranium concentration was within AERB recommended limit of 60µgl -1 . Average value observed in SW Punjab is around 3-4 times the value observed in W Punjab, whereas its value is more than 17 times the average value observed in NE region of Punjab. Statistical analysis of carcinogenic as well as non carcinogenic risks due to uranium have been evaluated for each studied district. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Embryonic turkey liver: activities of biotransformation enzymes and activation of DNA-reactive carcinogens

    International Nuclear Information System (INIS)

    Perrone, Carmen E.; Duan, Jian Dong; Jeffrey, Alan M.; Williams, Gary M.; Ahr, Hans-Juergen; Schmidt, Ulrich; Enzmann, Harald H.

    2004-01-01

    Avian embryos are a potential alternative model for chemical toxicity and carcinogenicity research. Because the toxic and carcinogenic effects of some chemicals depend on bioactivation, activities of biotransformation enzymes and formation of DNA adducts in embryonic turkey liver were examined. Biochemical analyses of 22-day in ovoturkey liver post-mitochondrial fractions revealed activities of the biotransformation enzymes 7-ethoxycoumarin de-ethylase (ECOD), 7-ethoxyresorufin de-ethylase (EROD), aldrin epoxidase (ALD), epoxide hydrolase (EH), glutathione S-transferase (GST), and UDP-glucuronyltransferase (GLUT). Following the administration of phenobarbital (24 mg/egg) on day 21, enzyme activities of ECOD, EROD, ALD, EH and GLUT, but not of GST, were increased by two-fold or higher levels by day 22. In contrast, acute administration of 3-methylcholanthrene (5 mg/egg) induced only ECOD and EROD activities. Bioactivation of structurally diverse pro-carcinogens was also examined using 32 P-postlabeling for DNA adducts. In ovoexposure of turkey embryos on day 20 of gestation to 2-acetylaminofluorene (AAF), 4,4'-methylenebis(2-chloroaniline) (MOCA), benzo[a]pyrene (BaP), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) resulted in the formation of DNA adducts in livers collected by day 21. Some of the DNA adducts had 32 P-postlabeling chromatographic migration patterns similar to DNA adducts found in livers from Fischer F344 rats exposed to the same pro-carcinogens. We conclude that 21-day embryonic turkey liver is capable of chemical biotransformation and activation of genotoxic carcinogens to form DNA adducts. Thus, turkey embryos could be utilized to investigate potential chemical toxicity and carcinogenicity. (orig.)

  14. Proposed changes in the classification of carcinogenic chemicals in the work area.

    Science.gov (United States)

    Neumann, H G; Thielmann, H W; Filser, J G; Gelbke, H P; Greim, H; Kappus, H; Norpoth, K H; Reuter, U; Vamvakas, S; Wardenbach, P; Wichmann, H E

    1997-12-01

    Carcinogenic chemicals in the work area are currently classified into three categories in Section III of the German List of MAK and BAT Values. This classification is based on qualitative criteria and reflects essentially the weight of evidence available for judging the carcinogenic potential of the chemicals. It is proposed that these Categories--IIIA1, IIIA2, and IIIB--be retained as Categories 1, 2, and 3, to conform with EU regulations. On the basis of our advancing knowledge of reaction mechanisms and the potency of carcinogens, it is now proposed that these three categories be supplemented with two additional categories. The essential feature of substances classified in the new categories is that exposure to these chemicals does not convey a significant risk of cancer to man, provided that an appropriate exposure limit (MAK value) is observed. It is proposed that chemicals known to act typically by nongenotoxic mechanisms and for which information is available that allows evaluation of the effects of low-dose exposures be classified in Category 4. Genotoxic chemicals for which low carcinogenic potency can be expected on the basis of dose-response relationships and toxicokinetics and for which risk at low doses can be assessed will be classified in Category 5. The basis for a better differentiation of carcinogens is discussed, the new categories are defined, and possible criteria for classification are described. Examples for Category 4 (1,4-dioxane) and Category 5 (styrene) are presented. The proposed changes in classifying carcinogenic chemicals in the work area are presented for further discussion.

  15. Chemical carcinogenic and mutagenic agents in the workplace, Poland, 2008–2010

    Directory of Open Access Journals (Sweden)

    Katarzyna Konieczko

    2013-04-01

    Full Text Available Background: The aim of this paper is to present a concise but comprehensive information on the occurrence of carcinogenic or mutagenic agents in Polish enterprises and the number of workers exposed to those agents reported to the central register by employers. Objectives and responsibilities of the register, as well as the range and methods of data gathering are discussed. Material and Methods: Data concerning carcinogenic or mutagenic chemical substances and technological processes reported to central register in 2008-2010 were analyzed. Results: In 2008-2010 more than 300 carcinogenic or mutagenic chemical substances were reported to the register. Approximately 2500 plants reported above 150 000 per-person-exposures annually. Among all technological processes regarded as occupational carcinogens, hardwood dusts exposure (about 660 companies; 11 000-13 000 exposed workers each year and exposure to polycyclic aromatic hydrocarbons (PAHs present in coal products (117-125 plantsl 3000 exposed per year were reported. Conclusions: The most widespread carcinogenic/mutagenic substances were: benzene, chromium(VI compounds: potassium dichromate and chromate, chromium(VI trioxide and other chromium compounds, ethylene oxide, asbestos, benzo[a]pyrene and gasoline. The highest number of men was exposed to particular PAHs and benzene , and the majority of women was exposed to benzene, potassium dichromate and chromate, acrylamide, ethylene oxide and gasoline. The lack of clear-cut definitione of occupational exposure to carcinogen creates a problem faced by employers in defining the accurate number of exposed workers. Med Pr 2013;64(2:181–192

  16. Application of the key characteristics of carcinogens in cancer hazard identification

    Science.gov (United States)

    Guyton, Kathryn Z; Rusyn, Ivan; Chiu, Weihsueh A; Corpet, Denis E; van den Berg, Martin; Ross, Matthew K; Christiani, David C; Beland, Frederick A; Smith, Martyn T

    2018-01-01

    Abstract Smith et al. (Env. Health Perspect. 124: 713, 2016) identified 10 key characteristics (KCs), one or more of which are commonly exhibited by established human carcinogens. The KCs reflect the properties of a cancer-causing agent, such as ‘is genotoxic,’ ‘is immunosuppressive’ or ‘modulates receptor-mediated effects,’ and are distinct from the hallmarks of cancer, which are the properties of tumors. To assess feasibility and limitations of applying the KCs to diverse agents, methods and results of mechanistic data evaluations were compiled from eight recent IARC Monograph meetings. A systematic search, screening and evaluation procedure identified a broad literature encompassing multiple KCs for most (12/16) IARC Group 1 or 2A carcinogens identified in these meetings. Five carcinogens are genotoxic and induce oxidative stress, of which pentachlorophenol, hydrazine and malathion also showed additional KCs. Four others, including welding fumes, are immunosuppressive. The overall evaluation was upgraded to Group 2A based on mechanistic data for only two agents, tetrabromobisphenol A and tetrachloroazobenzene. Both carcinogens modulate receptor-mediated effects in combination with other KCs. Fewer studies were identified for Group 2B or 3 agents, with the vast majority (17/18) showing only one or no KCs. Thus, an objective approach to identify and evaluate mechanistic studies pertinent to cancer revealed strong evidence for multiple KCs for most Group 1 or 2A carcinogens but also identified opportunities for improvement. Further development and mapping of toxicological and biomarker endpoints and pathways relevant to the KCs can advance the systematic search and evaluation of mechanistic data in carcinogen hazard identification. PMID:29562322

  17. Morpho-chemical characterization and surface properties of carcinogenic zeolite fibers

    International Nuclear Information System (INIS)

    Mattioli, Michele; Giordani, Matteo; Dogan, Meral; Cangiotti, Michela; Avella, Giuseppe; Giorgi, Rodorico; Dogan, A. Umran; Ottaviani, Maria Francesca

    2016-01-01

    Highlights: • Differently carcinogenic zeolite fibers were investigated combining physico-chemical methods. • For the first time, zeolite fibers were studied by means of the EPR technique using different spin probes. • The structural properties and the adsorption capability are function of different types and distributions of adsorption sites. • The interacting ability of erionite is higher than that of other fibrous zeolites. • The surface interacting properties may be related with the carcinogenicity of the zeolite fibers. - Abstract: Erionite belonging to the zeolite family is a human health-hazard, since it was demonstrated to be carcinogenic. Conversely, offretite family zeolites were suspected carcinogenic. Mineralogical, morphological, chemical, and surface characterizations were performed on two erionites (GF1, MD8) and one offretite (BV12) fibrous samples and, for comparison, one scolecite (SC1) sample. The specific surface area analysis indicated a larger availability of surface sites for the adsorption onto GF1, while SC1 shows the lowest one and the presence of large pores in the poorly fibrous zeolite aggregates. Selected spin probes revealed a high adsorption capacity of GF1 compared to the other zeolites, but the polar/charged interacting sites were well distributed, intercalated by less polar sites (Si–O–Si). MD8 surface is less homogeneous and the polar/charged sites are more interacting and closer to each other compared to GF1. The interacting ability of BV12 surface is much lower than that found for GF1 and MD8 and the probes are trapped in small pores into the fibrous aggregates. In comparison with the other zeolites, the non-carcinogenic SC1 shows a poor interacting ability and a lower surface polarity. These results helped to clarify the chemical properties and the surface interacting ability of these zeolite fibers which may be related to their carcinogenicity.

  18. Embryonic turkey liver: activities of biotransformation enzymes and activation of DNA-reactive carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Perrone, Carmen E.; Duan, Jian Dong; Jeffrey, Alan M.; Williams, Gary M. [New York Medical College, Department of Pathology, Valhalla (United States); Ahr, Hans-Juergen; Schmidt, Ulrich [Bayer AG, Institute of Toxicology, Wuppertal (Germany); Enzmann, Harald H. [Federal Institute for Drugs and Medical Devices, Bonn (Germany)

    2004-10-01

    Avian embryos are a potential alternative model for chemical toxicity and carcinogenicity research. Because the toxic and carcinogenic effects of some chemicals depend on bioactivation, activities of biotransformation enzymes and formation of DNA adducts in embryonic turkey liver were examined. Biochemical analyses of 22-day in ovoturkey liver post-mitochondrial fractions revealed activities of the biotransformation enzymes 7-ethoxycoumarin de-ethylase (ECOD), 7-ethoxyresorufin de-ethylase (EROD), aldrin epoxidase (ALD), epoxide hydrolase (EH), glutathione S-transferase (GST), and UDP-glucuronyltransferase (GLUT). Following the administration of phenobarbital (24 mg/egg) on day 21, enzyme activities of ECOD, EROD, ALD, EH and GLUT, but not of GST, were increased by two-fold or higher levels by day 22. In contrast, acute administration of 3-methylcholanthrene (5 mg/egg) induced only ECOD and EROD activities. Bioactivation of structurally diverse pro-carcinogens was also examined using {sup 32}P-postlabeling for DNA adducts. In ovoexposure of turkey embryos on day 20 of gestation to 2-acetylaminofluorene (AAF), 4,4'-methylenebis(2-chloroaniline) (MOCA), benzo[a]pyrene (BaP), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) resulted in the formation of DNA adducts in livers collected by day 21. Some of the DNA adducts had {sup 32}P-postlabeling chromatographic migration patterns similar to DNA adducts found in livers from Fischer F344 rats exposed to the same pro-carcinogens. We conclude that 21-day embryonic turkey liver is capable of chemical biotransformation and activation of genotoxic carcinogens to form DNA adducts. Thus, turkey embryos could be utilized to investigate potential chemical toxicity and carcinogenicity. (orig.)

  19. Metabolite profiles of common Stemphylium species

    DEFF Research Database (Denmark)

    Andersen, Birgitte; Solfrizzo, Michelle; Visconti, Angelo

    1995-01-01

    and identified by their chromatographic and spectroscopic data (Rf values, reflectance spectrum, retention index and ultraviolet spectrum). These metabolites have been used for the chemotaxonomical characterization of Stemphylium botryosum, S. herbarum, S. alfalfae, S. majusculum, S. sarciniforme, S. vesicarium...

  20. Detecting beer intake by unique metabolite patterns

    DEFF Research Database (Denmark)

    Gürdeniz, Gözde; Jensen, Morten Georg; Meier, Sebastian

    2016-01-01

    Evaluation of health related effects of beer intake is hampered by the lack of accurate tools for assessing intakes (biomarkers). Therefore, we identified plasma and urine metabolites associated with recent beer intake by untargeted metabolomics and established a characteristic metabolite pattern...... representing raw materials and beer production as a qualitative biomarker of beer intake. In a randomized, crossover, single-blinded meal study (MSt1) 18 participants were given one at a time four different test beverages: strong, regular and non-alcoholic beers and a soft drink. Four participants were...... assigned to have two additional beers (MSt2). In addition to plasma and urine samples, test beverages, wort and hops extract were analyzed by UPLC-QTOF. A unique metabolite pattern reflecting beer metabolome, including metabolites derived from beer raw material (i.e. N-methyl tyramine sulfate and the sum...

  1. METABOLITE CHARACTERIZATION IN SERUM SAMPLES FROM ...

    African Journals Online (AJOL)

    Preferred Customer

    Metabonomics offers a distinct advantage over other tests as it can be ... Metabolic profiling in heart disease has also been successfully ... resonances of the small metabolites showing fingerprints of serum metabolomic profile (Figure. 3).

  2. Secondary metabolites of cyanobacteria Nostoc sp.

    Science.gov (United States)

    Kobayashi, Akio; Kajiyama, Shin-Ichiro

    1998-03-01

    Cyanobacteria attracted much attention recently because of their secondary metabolites with potent biological activities and unusual structures. This paper reviews some recent studies on the isolation, structural, elucidation and biological activities of the bioactive compounds from cyanobacteria Nostoc species.

  3. Metabolite Profiling of Red Sea Corals

    KAUST Repository

    Ortega, Jovhana Alejandra

    2016-01-01

    that provide insights into the specific nature of the symbiosis. Our analysis also revealed aquatic pollutants, which suggests that metabolite profiling might be used for monitoring pollution levels and assessing environmental impact.

  4. Analysis of mutagenic and carcinogenic risks: nitrates, nitrites, N-Nitroso compounds. Comparison with radioactive risks

    International Nuclear Information System (INIS)

    Bittel, R.

    1987-07-01

    This report comes within the scope of the general studies on mutagenic and carcinogenic agents other than ionizing radiations. Through feeding, way of life and working activities, man is exposed to genotoxic risks of N-nitroso compounds (NNC). In spite of differences in the molecular modes of action, there exists some analogy between the effects of radiation exposures and those of NNC: DNA is the target in either instance. Unlike radiations, NNC are alkylating agents. The whole activation process of carcinogens arises from mechanisms leading to DNA repair [fr

  5. Prediction of Chemical Carcinogenicity in Rodents from in vitro Genetic Toxicity Assays

    Science.gov (United States)

    Tennant, Raymond W.; Margolin, Barry H.; Shelby, Michael D.; Zeiger, Errol; Haseman, Joseph K.; Spalding, Judson; Caspary, William; Resnick, Michael; Stasiewicz, Stanley; Anderson, Beth; Minor, Robert

    1987-05-01

    Four widely used in vitro assays for genetic toxicity were evaluated for their ability to predict the carcinogenicity of selected chemicals in rodents. These assays were mutagenesis in Salmonella and mouse lymphoma cells and chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells. Seventy-three chemicals recently tested in 2-year carcinogenicity studies conducted by the National Cancer Institute and the National Toxicology Program were used in this evaluation. Test results from the four in vitro assays did not show significant differences in individual concordance with the rodent carcinogenicity results; the concordance of each assay was approximately 60 percent. Within the limits of this study there was no evidence of complementarity among the four assays, and no battery of tests constructed from these assays improved substantially on the overall performance of the Salmonella assay. The in vitro assays which represented a range of three cell types and four end points did show substantial agreement among themselves, indicating that chemicals positive in one in vitro assay tended to be positive in the other in vitro assays. To help put this project into its proper context, we emphasize certain features of the study: 1) Standard protocols were used to mimic the major use of STTs worldwide--screening for mutagens and carcinogens; no attempt was made to optimize protocols for specific chemicals. 2) The 73 NTP chemicals and their 60% incidence of carcinogenicity are probably not representative of the universe of chemicals but rather reflect the recent chemical selection process for the NTP carcinogenicity assay. 3) The small, diverse group of chemicals precludes a meaningful evaluation of the predictive utility of chemical structure information. 4) The NTP is currently testing these same 73 chemicals in two in vivo STTs for chromosomal effects. 5) Complete data for an additional group of 30 to 40 NTP chemicals will be gathered on

  6. Participation of IPEN in the international program of information about occupational exposure to carcinogen risks

    International Nuclear Information System (INIS)

    Osores, Jose; Gonzales, Susana

    2014-01-01

    During 2014, the Peruvian Nuclear Energy Institute participated in the mapping of risks to carcinogens due to occupational exposure for our country through CAREX program because all radioactive substances are considered by the International Agency for Research Cancer as type 1 carcinogens (high risk) and the presence of these substances in the work environment are unknown to professionals from other institutions. This occasion allowed the incorporation of Natural Occurring Radioactive Materials (NORM) as indicators in all work activities that were not considered by the Energy and Mining Sector. (authors).

  7. Hydrophobicity and charge shape cellular metabolite concentrations.

    Directory of Open Access Journals (Sweden)

    Arren Bar-Even

    2011-10-01

    Full Text Available What governs the concentrations of metabolites within living cells? Beyond specific metabolic and enzymatic considerations, are there global trends that affect their values? We hypothesize that the physico-chemical properties of metabolites considerably affect their in-vivo concentrations. The recently achieved experimental capability to measure the concentrations of many metabolites simultaneously has made the testing of this hypothesis possible. Here, we analyze such recently available data sets of metabolite concentrations within E. coli, S. cerevisiae, B. subtilis and human. Overall, these data sets encompass more than twenty conditions, each containing dozens (28-108 of simultaneously measured metabolites. We test for correlations with various physico-chemical properties and find that the number of charged atoms, non-polar surface area, lipophilicity and solubility consistently correlate with concentration. In most data sets, a change in one of these properties elicits a ~100 fold increase in metabolite concentrations. We find that the non-polar surface area and number of charged atoms account for almost half of the variation in concentrations in the most reliable and comprehensive data set. Analyzing specific groups of metabolites, such as amino-acids or phosphorylated nucleotides, reveals even a higher dependence of concentration on hydrophobicity. We suggest that these findings can be explained by evolutionary constraints imposed on metabolite concentrations and discuss possible selective pressures that can account for them. These include the reduction of solute leakage through the lipid membrane, avoidance of deleterious aggregates and reduction of non-specific hydrophobic binding. By highlighting the global constraints imposed on metabolic pathways, future research could shed light onto aspects of biochemical evolution and the chemical constraints that bound metabolic engineering efforts.

  8. Urinary metabolites of tetrahydronorharman in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Greiner, B.; Rommelspacher, H.

    1982-01-01

    The metabolism of THN in the rat was studied in vivo by use of /sup 14/C-radiolabelled compound. Structures of major urinary metabolites were determined by exact spectral data. Their concentrations were measured by liquid scintillation counting. It was found that THN is submitted to endogenous transformation, and that the excreted derivatives form three groups of similar concentration: unchanged substance, hydroxylated/conjugated compounds, and aromatic metabolites. Structures and proposed pathways are summed in diagram.

  9. Urinary metabolites of tetrahydronorharman in the rat

    International Nuclear Information System (INIS)

    Greiner, B.; Rommelspacher, H.

    1982-01-01

    The metabolism of THN in the rat was studied in vivo by use of 14 C-radiolabelled compound. Structures of major urinary metabolites were determined by exact spectral data. Their concentrations were measured by liquid scintillation counting. It was found that THN is submitted to endogenous transformation, and that the excreted derivatives form three groups of similar concentration: unchanged substance, hydroxylated/conjugated compounds, and aromatic metabolites. Structures and proposed pathways are summed in diagram

  10. GPCR-Mediated Signaling of Metabolites

    DEFF Research Database (Denmark)

    Husted, Anna Sofie; Trauelsen, Mette; Rudenko, Olga

    2017-01-01

    microbiota target primarily enteroendocrine, neuronal, and immune cells in the lamina propria of the gut mucosa and the liver and, through these tissues, the rest of the body. In contrast, metabolites from the intermediary metabolism act mainly as metabolic stress-induced autocrine and paracrine signals...... and obesity. The concept of key metabolites as ligands for specific GPCRs has broadened our understanding of metabolic signaling significantly and provides a number of novel potential drug targets....

  11. High Level of Tobacco Carcinogen-Derived DNA Damage in Oral Cells Is an Independent Predictor of Oral/Head and Neck Cancer Risk in Smokers.

    Science.gov (United States)

    Khariwala, Samir S; Ma, Bin; Ruszczak, Chris; Carmella, Steven G; Lindgren, Bruce; Hatsukami, Dorothy K; Hecht, Stephen S; Stepanov, Irina

    2017-09-01

    Exposure to tobacco-specific nitrosamines (TSNA) and polycyclic aromatic hydrocarbons (PAH) is recognized to play an important role in the development of oral/head and neck squamous cell cancer (HNSCC). We recently reported higher levels of TSNA-associated DNA adducts in the oral cells of smokers with HNSCC as compared with cancer-free smokers. In this study, we further investigated the tobacco constituent exposures in the same smokers to better understand the potential causes for the elevated oral DNA damage in smokers with HNSCC. Subjects included cigarette smokers with HNSCC (cases, n = 30) and cancer-free smokers (controls, n = 35). At recruitment, tobacco/alcohol use questionnaires were completed, and urine and oral cell samples were obtained. Analysis of urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and N '-Nitrosonornicotine (NNN; TSNA biomarkers), 1-hydroxypyrene (1-HOP, a PAH), cotinine, 3'-hydroxycotinine, and the nicotine metabolite ratio (NMR) were performed. Cases and controls differed in mean age, male preponderance, and frequency of alcohol consumption (but not total alcoholic drinks). Univariate analysis revealed similar levels of NNN, 1-HOP, and cotinine between groups but, as reported previously, significantly higher DNA adduct formation in the cases. Multiple regression adjusting for potential confounders showed persistent significant difference in DNA adduct levels between cases and controls [ratio of geometric means, 20.0; 95% CI, 2.7-148.6). Our cohort of smokers with HNSCC demonstrates higher levels of TSNA-derived oral DNA damage in the setting of similar exposure to nicotine and tobacco carcinogens. Among smokers, DNA adduct formation may act as a predictor of eventual development of HNSCC that is independent of carcinogen exposure indicators. Cancer Prev Res; 10(9); 507-13. ©2017 AACR See related editorial by Johnson and Bauman, p. 489 . ©2017 American Association for Cancer Research.

  12. New metabolites of hongdenafil, homosildenafil and hydroxyhomosildenafil.

    Science.gov (United States)

    Yeo, Miseon; Park, Yujin; Lee, Heesang; Choe, Sanggil; Baek, Seung-Hoon; Kim, Hye Kyung; Pyo, Jae Sung

    2018-02-05

    Recently, illegal sildenafil analogues have emerged, causing serious social issues. In spite of the importance of sildenafil analogues, their metabolic profiles or clinical effects have not been reported yet. In this study, new metabolites of illegal sildenafil analogues such as hongdenafil, homosildenafil, and hydroxyhomosildenafil were determined using liquid chromatography quadrupole-time of flight mass spectrometry (LC-Q-TOF-MS) and tandem mass spectrometry (LC-Q-TOF-MS/MS). To prepare metabolic samples, in vitro and in vivo studies were performed. For in vivo metabolites analysis, urine and feces samples of rats treated with sildenafil analogues were analyzed. For in vitro metabolites analysis, human liver microsomes incubated with sildenafil analogues were extracted and analyzed. All metabolites were characterized by LC-Q-TOF-MS and LC-Q-TOF-MS/MS. As a result, five, six, and seven metabolites were determined in hongdenafil, homosildenafil, and hydroxyhomosildenafil treated samples, respectively. These results could be applied to forensic science and other analytical fields. Moreover, these newly identified metabolites could be used as fundamental data to determine the side effect and toxicity of illegal sildenafil analogues. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Metabolites of cannabidiol identified in human urine.

    Science.gov (United States)

    Harvey, D J; Mechoulam, R

    1990-03-01

    1. Urine from a dystonic patient treated with cannabidiol (CBD) was examined by g.l.c.-mass spectrometry for CBD metabolites. Metabolites were identified as their trimethylsilyl (TMS), [2H9]TMS, and methyl ester/TMS derivatives and as the TMS derivatives of the product of lithium aluminium deuteride reduction. 2. Thirty-three metabolites were identified in addition to unmetabolized CBD, and a further four metabolites were partially characterized. 3. The major metabolic route was hydroxylation and oxidation at C-7 followed by further hydroxylation in the pentyl and propenyl groups to give 1"-, 2"-, 3"-, 4"- and 10-hydroxy derivatives of CBD-7-oic acid. Other metabolites, mainly acids, were formed by beta-oxidation and related biotransformations from the pentyl side-chain and these were also hydroxylated at C-6 or C-7. The major oxidized metabolite was CBD-7-oic acid containing a hydroxyethyl side-chain. 4. Two 8,9-dihydroxy compounds, presumably derived from the corresponding epoxide were identified. 5. Also present were several cyclized cannabinoids including delta-6- and delta-1-tetrahydrocannabinol and cannabinol. 6. This is the first metabolic study of CBD in humans; most observed metabolic routes were typical of those found for CBD and related cannabinoids in other species.

  14. 39-week carcinogenicity study with cyclosporin A in XPA-/- mice, wild type mice and XPA-/-.P53+/- double transgenic mice. Part of the ILSI/HESI Program on Alternative Methods for Carcinogenicity Testing

    NARCIS (Netherlands)

    Beems RB; Kreijl CF van; Steeg H van; LPI; LEO

    2002-01-01

    The objective of this study was to evaluate the carcinogenic response of cyclosporin A in XPA-/- mice having a C57BL/6 background. XPA-/- mice are deficient in nucleotide excision repair and have shown increased susceptibility to genotoxic carcinogens and uv-light. The study was part of a world-wide

  15. Evaluation of the genotoxic potential of 3-monochloropropane-1,2-diol (3-MCPD) and its metabolites, glycidol and beta-chlorolactic acid, using the single cell gel/comet assay.

    Science.gov (United States)

    El Ramy, R; Ould Elhkim, M; Lezmi, S; Poul, J M

    2007-01-01

    3-monochloropropane-1,2-diol (3-MCPD) is a member of a group of chemicals known as chloropropanols. It is found in many foods and food ingredients as a result of food processing. 3-MCPD is regarded as a rat carcinogen known to induce Leydig-cell and mammary gland tumours in males and kidney tumours in both genders. The aim of our study was to clarify the possible involvement of genotoxic mechanisms in 3-MCPD induced carcinogenicity at the target organ level. For that purpose, we evaluated DNA damages in selected target (kidneys and testes) and non-target (blood leukocytes, liver and bone marrow) male rat organs by the in vivo alkaline single cell gel electrophoresis (comet) assay, 3 and 24 h after 3-MCPD oral administration to Sprague-Dawley and Fisher 344 adult rats. 3-MCPD may be metabolised to a genotoxic intermediate, glycidol, whereas the predominant urinary metabolite in rats following 3-MCPD administration is beta-chlorolactic acid. Therefore, we also studied the DNA damaging effects of 3-MCPD and its metabolites, glycidol and beta-chlorolactic acid, in the in vitro comet assay on CHO cells. Our results show the absence of genotoxic potential of 3-MCPD in vivo in the target as well as in the non-target organs. Glycidol, the epoxide metabolite, induced DNA damages in CHO cells. beta-Chlorolactic acid, the main metabolite of 3-MCPD in rats, was shown to be devoid of DNA-damaging effects in vitro in mammalian cells.

  16. Prediction of Local Ultimate Strain and Toughness of Trabecular Bone Tissue by Raman Material Composition Analysis

    Directory of Open Access Journals (Sweden)

    Roberto Carretta

    2015-01-01

    Full Text Available Clinical studies indicate that bone mineral density correlates with fracture risk at the population level but does not correlate with individual fracture risk well. Current research aims to better understand the failure mechanism of bone and to identify key determinants of bone quality, thus improving fracture risk prediction. To get a better understanding of bone strength, it is important to analyze tissue-level properties not influenced by macro- or microarchitectural factors. The aim of this pilot study was to identify whether and to what extent material properties are correlated with mechanical properties at the tissue level. The influence of macro- or microarchitectural factors was excluded by testing individual trabeculae. Previously reported data of mechanical parameters measured in single trabeculae under tension and bending and its compositional properties measured by Raman spectroscopy was evaluated. Linear and multivariate regressions show that bone matrix quality but not quantity was significantly and independently correlated with the tissue-level ultimate strain and postyield work (r=0.65–0.94. Principal component analysis extracted three independent components explaining 86% of the total variance, representing elastic, yield, and ultimate components according to the included mechanical parameters. Some matrix parameters were both included in the ultimate component, indicating that the variation in ultimate strain and postyield work could be largely explained by Raman-derived compositional parameters.

  17. Molar mass of poly(ethylene terephthalate) (PET) during ultimate uniaxial drawing

    NARCIS (Netherlands)

    Göschel, U.; Cools, P.J.C.H.

    2000-01-01

    The changes of the average molar mass Mw, Mn, Mz, and molar mass distributions during multistep uniaxial drawing of poly(ethylene terephthalate) (PET) to achieve ultimate mechanical properties have been studied in detail by means of size exclusion chromatography (SEC) with triple detection:

  18. Molar-Mass of Poly(Ethylene-Terephthalate) (PET) During Ultimate Uniaxial Drawing

    NARCIS (Netherlands)

    Göschel, A.G.P.U.; Cools, P.J.C.H.

    2000-01-01

    The changes of the average molar mass Mw, Mn, Mz, and molar mass distributions during multistep uniaxial drawing of poly(ethylene terephthalate) (PET) to achieve ultimate mechanical properties have been studied in detail by means of size exclusion chromatography (SEC) with triple detection:

  19. Prisoner Fasting as Symbolic Speech: The Ultimate Speech-Action Test.

    Science.gov (United States)

    Sneed, Don; Stonecipher, Harry W.

    The ultimate test of the speech-action dichotomy, as it relates to symbolic speech to be considered by the courts, may be the fasting of prison inmates who use hunger strikes to protest the conditions of their confinement or to make political statements. While hunger strikes have been utilized by prisoners for years as a means of protest, it was…

  20. Reliability analysis of production ships with emphasis on load combination and ultimate strength

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiaozhi

    1995-05-01

    This thesis deals with ultimate strength and reliability analysis of offshore production ships, accounting for stochastic load combinations, using a typical North Sea production ship for reference. A review of methods for structural reliability analysis is presented. Probabilistic methods are established for the still water and vertical wave bending moments. Linear stress analysis of a midships transverse frame is carried out, four different finite element models are assessed. Upon verification of the general finite element code ABAQUS with a typical ship transverse girder example, for which test results are available, ultimate strength analysis of the reference transverse frame is made to obtain the ultimate load factors associated with the specified pressure loads in Det norske Veritas Classification rules for ships and rules for production vessels. Reliability analysis is performed to develop appropriate design criteria for the transverse structure. It is found that the transverse frame failure mode does not seem to contribute to the system collapse. Ultimate strength analysis of the longitudinally stiffened panels is performed, accounting for the combined biaxial and lateral loading. Reliability based design of the longitudinally stiffened bottom and deck panels is accomplished regarding the collapse mode under combined biaxial and lateral loads. 107 refs., 76 refs., 37 tabs.

  1. Magnetic surfaces, particle orbits and neutral injection in conventional and ultimate torsatrons

    International Nuclear Information System (INIS)

    Anderson, D.T.; Derr, J.A.; Kruckewitt, T.; Shohet, J.L.; Rehker, S.; Tataronis, J.A.

    1979-01-01

    Capabilities in fully non-axisymmetric numerical methods have resulted in a parametric study of various conventional and ultimate torsatron configurations. No superbananas are found in torsatrons without local magnetic wells. Neutral injection calculations show that, if the vacuum magnetic surfaces are well defined, tangential injection is very efficient

  2. Study of ultimate heat sink to Angra-1,2 and 3 Nuclear Power Plants

    International Nuclear Information System (INIS)

    Moreira, R.M.; Pinto, A.M.F.

    1985-03-01

    This report presents the premises, results and conclusion of study done to ultimate heat sink of Angra 1,2 and 3 units, with base in postulated accidents that generate transient heat discharges to environment. It's explicitily presumed the eventuality of discharging heat water recirculation. (C.M.) [pt

  3. Method for ultimate disposition of borate containing radioactive wastes by vitrification

    International Nuclear Information System (INIS)

    Bege, D.; Faust, H.J.; Puthawala, A.; Stunkel, H.

    1984-01-01

    Method for the ultimate disposition of radioactive wastes by vitrification, in which weak to medium radioactive waste concentrates from borate-containing radioactive liquids are mixed with added glass-forming materials, maximally in a ratio of 1:3, and the mixture heated to obtain a glass-forming melt

  4. 26 CFR 48.6427-10 - Kerosene; claims by registered ultimate vendors (blocked pumps).

    Science.gov (United States)

    2010-04-01

    ... (blocked pumps). 48.6427-10 Section 48.6427-10 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE...; claims by registered ultimate vendors (blocked pumps). (a) Overview. This section provides rules under... allowed by section 6427(l)(5)(B)(i). These claims relate to kerosene sold from a blocked pump. Claims...

  5. Discussion of the Method to Determine the Ultimate Bearing Capacity of Soil Foundation

    Science.gov (United States)

    Du, Peng; Liu, Xiaoling; Zhang, Yangfu

    2017-12-01

    Combining literature examples, this paper has carried out Contrastive analysis of the theoretical formula method and finite element method about the ultimate bearing capacity of foundation, To verify rationality and superiority of the incremental load method in finite element ABAQUS in solving the bearing capacity of foundation soil. The study can provide certain reference for practical engineering calculation and analysis of foundation bearing capacity.

  6. Too many journals? Towards a theory of repeated rejections and ultimate acceptance

    NARCIS (Netherlands)

    Oosterhaven, Jan

    Under a set of reasonable assumptions, it is shown that all manuscripts submitted to any journal will ultimately be published, either by the first journal or by one of the following journals to which a manuscript is resubmitted. This suggests that low quality manuscripts may also be published, which

  7. A comparison of international criteria for the ultimate storage of radioactive wastes

    International Nuclear Information System (INIS)

    Mielke, H.

    1985-01-01

    In countries other than the Federal Republic of Germany and internationally there are no comprehensive codes referring to criteria and safety requirements except those of the IAEA and USA. In other countries there exist safety goals for the ultimate storage or for purely geological criteria. The degree of detailing regulations differs widely abroad and internationally. Safety goals abroad and internationally as well as measures for their realisation in the ultimate storage of radioactive wastes in deep geological formations are in line with the German safety goals. The IAEA refers to general aspects of geological, waste technology and ultimate storage technology criteria. In the USA, ultimate storage technology criteria have been quantified in part. The quantitative geological criteria existing in Great Britain and in the Netherlands are only relevant in as much as safety analyses must be performed for a specific site to provide evidence for the safety of this site. The comparison shows that most requirements pronounced abroad are also made for the Federal Republic of Germany. Some requirements are more specified in the Federal Republic of Germany, some are more detailed abroad. (orig./HP) [de

  8. proximate and ultimate analysis of fuel pellets from oil palm residues

    African Journals Online (AJOL)

    HOD

    Keywords: Oil Palm Residues, Fuel Pellets, Proximate Analysis, Ultimate Analysis. 1. INTRODUCTION ... Pelletizing of this biomass resources into pellets is a way of ensuring a ... demand for pellets [3], and alternative feed-stocks such as palm kernel ... agro-residues, selection of the best pellets has to be made based on ...

  9. 7 CFR 4280.29 - Supplemental financing required for the Ultimate Recipient Project.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Supplemental financing required for the Ultimate Recipient Project. 4280.29 Section 4280.29 Agriculture Regulations of the Department of Agriculture... AND GRANTS Rural Economic Development Loan and Grant Programs § 4280.29 Supplemental financing...

  10. Brain metabolite levels and language abilities in preschool children.

    Science.gov (United States)

    Lebel, Catherine; MacMaster, Frank P; Dewey, Deborah

    2016-10-01

    Language acquisition occurs rapidly during early childhood and lays the foundation for future reading success. However, little is known about the brain-language relationships in young children. The goal of this study was to investigate relationships between brain metabolites and prereading language abilities in healthy preschool-aged children. Participants were 67 healthy children aged 3.0-5.4 years scanned on a 3T GE MR750w MRI scanner using short echo proton spectroscopy with a voxel placed in the anterior cingulate gyrus ( n  = 56) and/or near the left angular gyrus ( n  = 45). Children completed the NEPSY-II Phonological Processing and Speeded Naming subtests at the same time as their MRI scan. We calculated glutamate, glutamine, creatine/phosphocreatine, choline, inositol, and NAA concentrations, and correlated these with language skills. In the anterior cingulate, Phonological Processing Scaled Scores were significantly correlated with glutamate, creatine, and inositol concentrations. In the left angular gyrus, Speeded Naming Combined Scaled Scores showed trend correlations with choline and glutamine concentrations. For the first time, we demonstrate relationships between brain metabolites and prereading language abilities in young children. Our results show relationships between language and inositol and glutamate that may reflect glial differences underlying language function, and a relationship of language with creatine. The trend between Speeded Naming and choline is consistent with previous research in older children and adults; however, larger sample sizes are needed to confirm whether this relationship is indeed significant in young children. These findings help understand the brain basis of language, and may ultimately lead to earlier and more effective interventions for reading disabilities.

  11. The relevance of "non-relevant metabolites" from plant protection products (PPPs) for drinking water: the German view.

    Science.gov (United States)

    Dieter, Hermann H

    2010-03-01

    "Non-relevant metabolites" are those degradation products of plant protection products (PPPs), which are devoid of the targeted toxicities of the PPP and devoid of genotoxicity. Most often, "non-relevant metabolites" have a high affinity to the aquatic environment, are very mobile within this environment, and, usually, are also persistent. Therefore, from the point of drinking water hygiene, they must be characterized as "relevant for drinking water" like many other hydrophilic/polar environmental contaminants of different origins. "Non-relevant metabolites" may therefore penetrate to water sources used for abstraction of drinking water and may thus ultimately be present in drinking water. The presence of "non-relevant metabolites" and similar trace compounds in the water cycle may endanger drinking water quality on a long-term scale. During oxidative drinking water treatment, "non-relevant metabolites" may also serve as the starting material for toxicologically relevant transformation products similar to processes observed by drinking water disinfection with chlorine. This hypothesis was recently confirmed by the detection of the formation of N-nitroso-dimethylamine from ozone and dimethylsulfamide, a "non-relevant metabolite" of the fungicide tolylfluanide. In order to keep drinking water preferably free of "non-relevant metabolites", the German drinking water advisory board of the Federal Ministry of Health supports limiting their penetration into raw and drinking water to the functionally (agriculturally) unavoidable extent. On this background, the German Federal Environment Agency (UBA) recently has recommended two health related indication values (HRIV) to assess "non-relevant metabolites" from the view of drinking water hygiene. Considering the sometimes incomplete toxicological data base for some "non-relevant metabolites", HRIV also have the role of health related precautionary values. Depending on the completeness and quality of the toxicological

  12. Structure-activity relationships for the fluorescence of ochratoxin A: Insight for detection of ochratoxin A metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Frenette, Christine; Paugh, Robert J. [Departments of Chemistry and Toxicology, University of Guelph, Guelph, Ontario, N1G 2W1 (Canada); Tozlovanu, Mariana; Juzio, Maud [ENSAT, UMR CNRS 5503, 1 Avenue Agrobiopole 31326 Auzeville-Tolosane (France); Pfohl-Leszkowicz, Annie [ENSAT, UMR CNRS 5503, 1 Avenue Agrobiopole 31326 Auzeville-Tolosane (France)], E-mail: leszkowicz@ensat.fr; Manderville, Richard A. [Departments of Chemistry and Toxicology, University of Guelph, Guelph, Ontario, N1G 2W1 (Canada)], E-mail: rmanderv@uoguelph.ca

    2008-06-09

    Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium that is widely found as a contaminant of food products. The toxin is a renal carcinogen in male rats, the cause of mycotoxicoses in pigs and has been associated with chronic human kidney diseases. Bioactivation has been implicated in OTA-mediated toxicity, although inconsistent results have been reported, due, in part, to the difficulty in detecting OTA metabolites in vivo. Liquid chromatography (LC) coupled with fluorescence detection (FLD) is the most widely used analytical detection method for OTA. Under acidic conditions the toxin generates blue fluorescence (465 nm) that is due to an excited state intramolecular proton transfer (ESIPT) process that generates an emissive keto tautomer. Disruption of this ESIPT process quenches fluorescence intensity and causes a blue shift in emission maxima. The aim of the present study was to determine the impact of the C5-chlorine atom, the lactone moiety and the amide bond on OTA fluorescence and derive optical parameters for OTA metabolites that have been detected in vitro. Our results highlight the limitations of LC/FLD for OTA metabolites that do not undergo ESIPT. For emissive derivatives, our absorption and emission data improves the sensitivity of LC/FLD (3-4-fold increase in the limit of detection (LOD)) for OTA analogues bearing a C5-OH group, such as the hydroquinone (OTHQ) metabolite and the glutathione conjugate of OTA (OTA-GSH). This increased sensitivity may facilitate the detection of OTA metabolites bearing a C5-OH group in biological fluids and enhance our understanding of OTA-mediated toxicity.

  13. Novel adducts from the reaction of 1-chloro-3-buten-2-one with 2'-deoxyguanosine. Structural characterization and potential as tools to investigate 1,3-butadiene carcinogenicity.

    Science.gov (United States)

    Zheng, Jin; Li, Yan; Yu, Ying-Xin; An, Jing; Zhang, Xin-Yu; Elfarra, Adnan A

    2015-01-25

    1-Chloro-3-buten-2-one (CBO) is a potential reactive metabolite of 1,3-butadiene (BD), a carcinogenic air pollutant. To develop tools that may help investigate the role of CBO in BD carcinogenicity and to develop biomarkers that can be used to assess BD exposure, the reaction of CBO with 2'-deoxyguanosine (dG) under in vitro physiological conditions (pH 7.4, 37°C) was investigated and the products (designated as CG-1, CG-2, CG-3, CG-4, CG-5, and CG-6 based on their retention times on HPLC) were characterized by MS and NMR spectroscopy. The structures of CG-1, CG-2, CG-3, and CG-4 were 1,N2-(3-hydroxy-3-hydroxymethylpropan-1,3-diyl)-2'-deoxyguanosine, N7-(4-chloro-3-oxobutyl)-2'-deoxyguanosine, N7,8-(3-hydroxy-3-chloromethylpropan-1,3-diyl)guanine and N2-(4-chloro-3-oxobutyl)-2'-deoxyguanosine, respectively. CG-5 and CG-6, a pair of diastereomers, were characterized as 1,N2-(3-hydroxy-3-chloromethylpropan-1,3-diyl)-2'-deoxyguanosine. CG-1 was stable under in vitro physiological conditions, whereas CG-2, CG-3, CG-4, and CG-5/6 were unstable and exhibited the half-lives at CG-2 decomposed primarily via a retro-Michael reaction to produce dG and CBO, with only a small fraction of CG-2 degrading to CG-3. Decomposition of CG-4 proceeded via a cyclization reaction and/or replacement of the chlorine atom by a hydroxyl group to form 1,N2-(1-hydroxy-1-hydroxymethylpropan-1,3-diyl)-2'-deoxyguanosine (CG-4D1) and N(2)-(4-hydroxy-3-oxobutyl)-2'-deoxyguanosine (CG-4D2), whereas decomposition of CG-5/6 yielded CG-1. Collectively, the newly characterized CBO adducts could be used to investigate the role of CBO in the mechanism of BD carcinogenicity and could also be used to develop biomarkers for BD exposure. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Induction of biotransformation enzymes by the carcinogenic air-pollutant 3-nitrobenzanthrone in liver, kidney and lung, after intra-tracheal instillation in rats.

    Science.gov (United States)

    Mizerovská, Jana; Dračínská, Helena; Frei, Eva; Schmeiser, Heinz H; Arlt, Volker M; Stiborová, Marie

    2011-02-28

    3-Nitrobenzanthrone (3-NBA), a carcinogenic air pollutant, was investigated for its ability to induce cytochrome P450 (CYP) 1A1/2 and NAD(P)H:quinone oxidoreductase (NQO1) in liver, kidney and lung of rats treated by intra-tracheal instillation. The organs used were from a previous study performed to determine the persistence of 3-NBA-derived DNA adducts in target and non-target tissues (Bieler et al., Carcinogenesis 28 (2007) 1117-1121, [22]). NQO1 is the enzyme reducing 3-NBA to N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA) and CYP1A enzymes oxidize a human metabolite of 3-NBA, 3-aminobenzanthrone (3-ABA), to yield the same reactive intermediate. 3-NBA and 3-ABA are both activated to species forming DNA adducts by cytosols and/or microsomes isolated from rat lung, the target organ for 3-NBA carcinogenicity, and from liver and kidney. Each compound generated the same five DNA adducts detectable by (32)P-postlabelling. When hepatic cytosols from rats treated with 0.2 or 2mg/kg body weight of 3-NBA were incubated with 3-NBA, DNA adduct formation was 3.2- and 8.6-fold higher, respectively, than in incubations with cytosols from control animals. Likewise, cytosols isolated from lungs and kidneys of rats exposed to 3-NBA more efficiently activated 3-NBA than those of control rats. This increase corresponded to an increase in protein levels and enzymatic activities of NQO1. Incubations of hepatic, pulmonary or renal microsomes of 3-NBA-treated rats with 3-ABA led to an 9.6-fold increase in DNA-adduct formation relative to controls. The highest induction in DNA-adduct levels was found in lung. The stimulation of DNA-adduct formation correlated with expression of CYP1A1/2 induced by the intra-tracheal instillation of 3-NBA. The results demonstrate that 3-NBA induces NQO1 and CYP1A1/2 in livers, lungs and kidneys of rats after intra-tracheal instillation, thereby enhancing its own genotoxic and carcinogenic potential. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. Research results from inquiries into the carcinogenic effects of surface active agents. On the non-hazardous nature of ABS

    Energy Technology Data Exchange (ETDEWEB)

    Toyama, Shinichi

    1963-03-15

    Although the trial-production alkylbenzene used behaved atypically and so is presumed to contain complex carcinogenic hydrocarbon-like impurity by-products, commercially available alkylbenzenes generally did not possess carcinogenic properties. These substances used in alkylbenzene sulfonate production have very small promotive characteristics comparable to croton oil. However, alkylbenzene sulfonate demonstrated no cancer producing properties. (DT)

  16. Carcinogenic risk assessment and management of ionising radiation, asbestos and nickel: a comparative approach

    International Nuclear Information System (INIS)

    Schneider, T.; Lepicard, S.; Oudiz, A.; Heriard Dubreuil, G.; Gadbois, S.

    2000-01-01

    assessment of individual exposures and their measurements are difficult to achieve. In this context, the ALARA approach refers mainly to the adoption of good practices. In this study, a quantitative comparison of risks in the various sectors is less important than a qualitative comparison of the risk-assessment and management approaches. It is felt that identifying similarities and differences is an objective in its own right in that it provides a basis on which to challenge, where necessary, some commonly-held beliefs regarding the advances that some sectors are assumed to have over others. The collected data reveal some significant similarities in the principles on which the assessment and management of risks of low-level exposure are based. At the same time, the procedures which are actually used in practice, despite being based on relatively distinct 'instruments', ultimately produce results that are not dissimilar and that in general reflect the shared concern to devise reasonable' solutions with regard to the prevention of carcinogenic risks. (author)

  17. In Vivo acrylamide exposure may cause severe toxicity to mouse oocytes through its metabolite glycidamide.

    Directory of Open Access Journals (Sweden)

    Duru Aras

    Full Text Available High acrylamide (ACR content in heat-processed carbohydrate-rich foods, as well as roasted products such as coffee, almonds etc., has been found to be as a risk factor for carcinogenicity and genotoxicity by The World Health Organization. Glycidamide (GLY, the epoxide metabolite of ACR, is processed by the cytochrome P-450 enzyme system and has also been found to be a genotoxic agent. The aim of this study was to determine whether ACR and/or GLY have any detrimental effect on the meiotic cell division of oocytes. For this purpose, germinal vesicle-stage mouse oocytes were treated with 0, 100, 500, or 1000 μM ACR or 0, 25, or 250 μM GLY in vitro. In vivo experiments were performed after an intraperitoneal injection of 25 mg/kg/day ACR of female BALB/c mice for 7 days. The majority of in vitro ACR-treated oocytes reached the metaphase-II stage following 18 hours of incubation, which was not significantly different from the control group. Maturation of the oocytes derived from in vivo ACR-treated mice was impaired significantly. Oocytes, reaching the M-II stage in the in vivo ACR-treated group, were characterized by a decrease in meiotic spindle mass and an increase in chromosomal disruption. In vitro GLY treatment resulted in the degeneration of all oocytes, indicating that ACR toxicity on female germ cells may occur through its metabolite, GLY. Thus, ACR exposure must be considered, together with its metabolite GLY, when female fertility is concerned.

  18. Moving forward in carcinogenicity assessment : Report of an EURL ECVAM/ESTIV workshop

    NARCIS (Netherlands)

    Corvi, Raffaella; Madia, Federica; Guyton, Kathryn Z; Kasper, Peter; Rudel, Ruthann; Colacci, Annamaria; Kleinjans, Jos; Jennings, Paul

    2017-01-01

    There is an increased need to develop novel alternative approaches to the two-year rodent bioassay for the carcinogenicity assessment of substances where the rodent bioassay is still a basic requirement, as well as for those substances where animal use is banned or limited or where information gaps

  19. Search for Internal Cancers in Mice Tattooed with Inks of High Contents of Potential Carcinogens

    DEFF Research Database (Denmark)

    Sepehri, Mitra; Lerche, Catharina M; Hutton Carlsen, Katrina

    2017-01-01

    on the Danish market due to the measured contents of potential carcinogens; benzo(a)pyrene and 2-anisidine, respectively. The mice were housed for 1 year after tattooing, and autopsy study on internal organs was performed. Tissue samples were systematically taken from major organs for screening of subclinical...

  20. Repair of DNA treated with lambda-irradiation and chemical carcinogens. Progress report, 1984-1985

    International Nuclear Information System (INIS)

    Goldthwait, D.A.

    1985-01-01

    Research progress is reported in the following areas: (1) DNA repair in HeLa cells; (2) a search for human transposable elements; (3) the effect of radiation and carcinogens on the activation of LTR sequences; and (4) studies on oncogenes of central nervous system tumors

  1. Morpho-chemical characterization and surface properties of carcinogenic zeolite fibers.

    Science.gov (United States)

    Mattioli, Michele; Giordani, Matteo; Dogan, Meral; Cangiotti, Michela; Avella, Giuseppe; Giorgi, Rodorico; Dogan, A Umran; Ottaviani, Maria Francesca

    2016-04-05

    Erionite belonging to the zeolite family is a human health-hazard, since it was demonstrated to be carcinogenic. Conversely, offretite family zeolites were suspected carcinogenic. Mineralogical, morphological, chemical, and surface characterizations were performed on two erionites (GF1, MD8) and one offretite (BV12) fibrous samples and, for comparison, one scolecite (SC1) sample. The specific surface area analysis indicated a larger availability of surface sites for the adsorption onto GF1, while SC1 shows the lowest one and the presence of large pores in the poorly fibrous zeolite aggregates. Selected spin probes revealed a high adsorption capacity of GF1 compared to the other zeolites, but the polar/charged interacting sites were well distributed, intercalated by less polar sites (Si-O-Si). MD8 surface is less homogeneous and the polar/charged sites are more interacting and closer to each other compared to GF1. The interacting ability of BV12 surface is much lower than that found for GF1 and MD8 and the probes are trapped in small pores into the fibrous aggregates. In comparison with the other zeolites, the non-carcinogenic SC1 shows a poor interacting ability and a lower surface polarity. These results helped to clarify the chemical properties and the surface interacting ability of these zeolite fibers which may be related to their carcinogenicity. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Site-specific induction of nuclear anomalies (apoptotic bodies and micronuclei) by carcinogens in mice

    International Nuclear Information System (INIS)

    Ronen, A.; Heddle, J.A.

    1984-01-01

    The usefulness of nuclear anomalies (NA) as a short-term test for indication of carcinogens in the mouse colon has been suggested previously by experiments in which colon-specific carcinogens induced NA in the colon, whereas non-colon carcinogens were, in general, impotent in that organ. We have extended this work to other sites in the digestive tract of female C57BL/6 mice treated with gamma-rays, 1,2-dimethylhydrazine dihydrochloride, or N-methylnitrosourea. Each agent induced NA at all of the sites examined. The frequency of NA at different times after treatment depended upon both the agent used and the site examined. 1,2-Dimethylhydrazine dihydrochloride (which is known to induce tumors predominantly in the colon) induces NA with the highest efficiency (relative to gamma-rays) in the descending colon. N-Methylnitrosourea (which induces tumors mainly in the forestomach) induces NA with the highest efficiency in the forestomach. These results further support the usefulness of the assay in that the frequency of NA produced at the various sites by 1,2-dimethylhydrazine dihydrochloride and N-methylnitrosourea correlates with that found in the carcinogenicity studies

  3. Methodology in use for the assessment of carcinogenic risk. II. Radiation. Oncology overview

    International Nuclear Information System (INIS)

    1983-04-01

    Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories throughout the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Assessment of carcinogenic risk from environmental and occupational exposures to ionizing radiation; Assessment of carcinogenic risk from exposure to ionizing radiation used for medical diagnosis or treatment; Assessment of carcinogenic risk from exposure to ionizing radiation following nuclear bomb explosions; Comparison of risk from radiation sources with risk from nonradiation sources; Experimental studies to assess risk of carcinogenesis following exposure to ionizing radiation; Theoretical aspects of dose-response relationships in the assessment of carcinogenic risk from exposure to ionizing radiation; Public policy and standards for acceptable risk from exposure to ionizing radiation; General reviews on the assessment of risk from exposure to ionizing radiation

  4. Carcinogenic agents present in the atmosphere and incidence of primary lung tumors in mice

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, J A

    1939-01-01

    Exposure of mice to suspended benzene extracts of exhaust pipe soot from engine burning heavy oil for once/hr, 6 hr/day, for a lifetime, produced a slight increase in lung tumors whereas chimney soot had no effect. Conversely, chimney soot extract painted on skin was judged carcinogenic, whereas exhaust soot did not produce cancer.

  5. Asian Americans and disproportionate exposure to carcinogenic hazardous air pollutants: A national study.

    Science.gov (United States)

    Grineski, Sara E; Collins, Timothy W; Morales, Danielle X

    2017-07-01

    Studies have demonstrated disparate exposures to carcinogenic hazardous air pollutants (HAPs) in neighborhoods with high densities of Black and Hispanic residents in the US. Asians are the fastest growing racial/ethnic group in the US, yet they have been underemphasized in previous studies of environmental health and injustice. This cross-sectional study investigated possible disparities in residential exposure to carcinogenic HAPs among Asian Americans, including Asian American subgroups in the US (including all 50 states and the District of Columbia, n = 71,208 US census tracts) using National Air Toxics Assessment and US Census data. In an unadjusted analysis, Chinese and Korean Americans experience the highest mean cancer risks from HAPs, followed by Blacks. The aggregated Asian category ranks just below Blacks and above Hispanics, in terms of carcinogenic HAP risk. Multivariate models adjusting for socioeconomic status, population density, urban location, and geographic clustering show that an increase in proportion of Asian residents in census tracts is associated with significantly greater cancer risk from HAPs. Neighborhoods with higher proportions (as opposed to lower proportions) of Chinese, Korean, and South Asian residents have significantly greater cancer risk burdens relative to Whites. Tracts with higher concentrations of Asians speaking a non-English language and Asians that are US-born have significantly greater cancer risk burdens. Asian Americans experience substantial residential exposure to carcinogenic HAPs in US census tracts and in the US more generally. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Myricetin stimulates the absorption of the pro-carcinogen PhIP

    NARCIS (Netherlands)

    Schutte, M.E.; Sandt, J.J.M. van de; Alink, G.M.; Groten, J.P.; Rietjens, I.M.C.M.

    2006-01-01

    The effect of the flavonoid myricetin on the transport of the pro-carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through differentiated Caco-2 monolayers, a model for the intestinal epithelium, is described. Myricetin causes an increase of the transport of PhIP from the apical to

  7. Approaches to the risk assessment of genotoxic carcinogens in food: a critical appraisal.

    NARCIS (Netherlands)

    O'Brien, J; Renwick, A G; Constable, A; Dybing, Erik; Müller, D J G; Schlatter, J; Slob, Wout; Tueting, W; Benthem, Jan van; Williams, G M; Wolfreys, A

    2006-01-01

    The present paper examines the particular difficulties presented by low levels of food-borne DNA-reactive genotoxic carcinogens, some of which may be difficult to eliminate completely from the diet, and proposes a structured approach for the evaluation of such compounds. While the ALARA approach is

  8. Mutagenicity of food-derived carcinogens and the effect of antioxidant vitamins.

    Science.gov (United States)

    Montgomery, Beverly A; Murphy, Jessica; Chen, James J; Desai, Varsha G; McGarrity, Lynda; Morris, Suzanne M; Casciano, Daniel A; Aidoo, Anane

    2002-01-01

    The food-derived heterocyclic amines (HCAs) 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are mutagenic in the Ames test and produce tumors in laboratory animals, including monkeys. These HCAs have also been shown to induce gene mutations in vivo. To assess the antimutagenic effects of dietary antioxidant vitamins, beta-carotene, ascorbic acid (vitamin C), and alpha-tocopherol (vitamin E), on food-borne mutagenes/carcinogens, we evaluated the mutagenic activity of the compounds alone or combined with antioxidant vitamins. We utilized the rat lymphocyte mutation assay at the hypoxanthine guanine phosphoribosyl transferase (Hprt) locus. Female Fischer 344 rats treated with different doses (0, 2.5, 5.0, 25.0, and 50.0 mg/kg) of the carcinogens were sacrificed 5 wk after mutagen treatment. Although IQ and MeIQ slightly increased mutation frequency (MF) at some doses, a significant (P carcinogen metabolism would be affected by ingestion of vitamins. The activities of endogenous detoxification enzymes, glutathione S-transferase and glutathione peroxidase (GPx), were thus examined. Intake of beta-carotene and vitamin C without the carcinogen resulted in an increase (P food or taken as supplements could, in part, counteract such mutagenic activities.

  9. Biomarkers of exposure to carcinogenic PAHs and their relationship with environmental factors

    Czech Academy of Sciences Publication Activity Database

    Taioli, E.; Šrám, Radim; Binková, Blanka; Kalina, I.; Popov, T. A.; Garte, S.; Farmer, P. B.

    2007-01-01

    Roč. 620, - (2007), s. 16-21 ISSN 0027-5107 Grant - others:EU(GB) 2000-00091 Institutional research plan: CEZ:AV0Z50390512 Source of funding: R - rámcový projekt EK Keywords : DNA adducts * air pollution * carcinogenic PAHs Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 4.159, year: 2007

  10. An evaluation of the mode of action framework for mutagenic carcinogens: Chromium (VI): SOT.

    Science.gov (United States)

    In response to the 2005 revised U.S Environmental Protection Agency’s (EPA) Cancer Guidelines, a strategy is being developed to determine whether a carcinogen operates through a mutagenic mode of action (MOA). This information is necessary for EPA to decide whether age-dependent ...

  11. An evaluation of the mode of action framework for mutagenic carcinogens: chromium (VI)

    Science.gov (United States)

    In response to the 2005 revised U.S Environmental Protection Agency’s (EPA) Cancer Guidelines, a strategy is being developed to determine whether a carcinogen operates through a mutagenic mode of action (MOA). This information is necessary for EPA to decide whether age-dependent ...

  12. Carcinogens, Teratogens and Mutagens: Their Impact on Occupational Health, Particularly for Women in Veterinary Medicine.

    Science.gov (United States)

    Milligan, J. E.; And Others

    1983-01-01

    Pregnant women, especially those working in veterinary medicine, face occupational health/disease risks from mutagens, teratogens, and carcinogens. These hazards can be placed into three categories: physical, chemical, and biological. Each of these hazards is discussed with examples. (Author/JN)

  13. TLR2 Controls Intestinal Carcinogen Detoxication by CYP1A1

    DEFF Research Database (Denmark)

    Do, Khoa; Fink, Lisbeth Nielsen; Jensen, Thomas Elbenhardt

    2012-01-01

    of ligands for TLR2 of bacterial origin seems to be crucial for detoxication of luminal carcinogens by CYP1A1 in the intestine. This unprecedented finding indicates a complex interplay between the immune system of the host and intestinal bacteria with detoxication mechanisms. This highlights the relevance...

  14. Production of carcinogenic acetaldehyde by Candida albicans from patients with potentially malignant oral mucosal disorders.

    Science.gov (United States)

    Gainza-Cirauqui, M L; Nieminen, M T; Novak Frazer, L; Aguirre-Urizar, J M; Moragues, M D; Rautemaa, R

    2013-03-01

    Production of carcinogenic acetaldehyde by Candida has been suggested to contribute to epithelial dysplasia and oral carcinogenesis. Oral lichen planus (OLP), oral lichenoid lesion (OLL) and oral leukoplakia (OL) are potentially carcinogenic oral diseases where colonisation by Candida is common, but acetaldehyde production by Candida has not been studied. Acetaldehyde production in ethanol (11 mM), glucose (100 mM), ethanol-glucose (11 mM and 100 mM) or red wine (1200 mM ethanol) incubation by Candida albicans from patients with OLL (n = 6), OLP (n = 16), OL (n = 6) and controls (n = 6) was measured by gas chromatography. Participants completed a questionnaire regarding their smoking habits and alcohol consumption. All Candida albicans isolates produced potentially carcinogenic levels of acetaldehyde (>100 μM) in all incubations containing ethanol. The control group isolates produced the highest acetaldehyde levels. Isolates from smokers produced more acetaldehyde in all incubations than those from non-smokers. The difference was significant in ethanol-glucose incubation. Isolates from patients who were both smokers and drinkers produced the highest amounts when incubated in ethanol, ethanol-glucose and wine. Candida albicans isolated from potentially carcinogenic oral diseases can produce mutagenic amounts of acetaldehyde. Cigarette smoking and alcohol consumption may favour adaptational changes resulting in the upregulation of candidal acetaldehyde metabolism. © 2012 John Wiley & Sons A/S. All rights reserved.

  15. 78 FR 4419 - Draft Report on Carcinogens Monographs for 1-Bromopropane and Cumene; Availability of Documents...

    Science.gov (United States)

    2013-01-22

    ... Monographs for 1-Bromopropane and Cumene; Availability of Documents; Request for Comments; Notice of Meeting SUMMARY: Peer review meeting of the Draft Report on Carcinogens (RoC) Monographs for 1-Bromopropane and... monographs will be available by January [[Page 4420

  16. SYN-JEM : A Quantitative Job-Exposure Matrix for Five Lung Carcinogens

    NARCIS (Netherlands)

    Peters, Susan; Vermeulen, Roel; Portengen, L??tzen; Olsson, Ann; Kendzia, Benjamin; Vincent, Raymond; Savary, Barbara; LavouCrossed Sign, Jcrossed D Signr??me; Cavallo, Domenico; Cattaneo, Andrea; Mirabelli, Dario; Plato, Nils; Fevotte, Joelle; Pesch, Beate; Br??ning, Thomas; Straif, Kurt; Kromhout, Hans

    2016-01-01

    OBJECTIVE The use of measurement data in occupational exposure assessment allows more quantitative analyses of possible exposure-response relations. We describe a quantitative exposure assessment approach for five lung carcinogens (i.e. asbestos, chromium-VI, nickel, polycyclic aromatic hydrocarbons

  17. 78 FR 57868 - Nominations to the Report on Carcinogens; Request for Information

    Science.gov (United States)

    2013-09-20

    ... Carcinogens (ORoC) requests information on 20 substances, mixtures, and exposure circumstances (collectively... for the following topics: (1) data on current production, use patterns, and human exposure; (2... (CAS No. 108-10-1) Nickel nanoparticles Nitro polycyclic aromatic hydrocarbons (PAH) as a class...

  18. SYN-JEM : A Quantitative Job-Exposure Matrix for Five Lung Carcinogens

    NARCIS (Netherlands)

    Peters, Susan; Vermeulen, Roel; Portengen, Lützen; Olsson, Ann C.; Kendzia, Benjamin; Vincent, Raymond; Savary, Barbara; LavouCrossed Sign, Jcrossed D.Signrôme; Cavallo, Domenico; Cattaneo, Andrea; Mirabelli, Dario; Plato, Nils; Fevotte, Joelle; Pesch, Beate; Brüning, Thomas; Straif, Kurt; Kromhout, Hans

    2016-01-01

    Objective: The use of measurement data in occupational exposure assessment allows more quantitative analyses of possible exposure-response relations. We describe a quantitative exposure assessment approach for five lung carcinogens (i.e. asbestos, chromium-VI, nickel, polycyclic aromatic

  19. 78 FR 67372 - Evaluation of Trichloroethylene for the Report on Carcinogens; Request for Nominations of...

    Science.gov (United States)

    2013-11-12

    ... Trichloroethylene for the Report on Carcinogens; Request for Nominations of Scientific Experts for Proposed Webinar... association of exposure to trichloroethylene (TCE) and cancer. DATES: The deadline for receipt of nominations.../Trichloroethylene.pdf ). The NTP selected TCE for evaluation to determine whether a change in its listing status in...

  20. Critical effective methods to detect genotoxic carcinogens and neoplasm-promoting agents.

    Science.gov (United States)

    Weisburger, J H; Williams, G M

    1991-01-01

    Neoplasia in fish can result from contamination of waters with carcinogens and promoters. Cancer in fish, therefore, is a possible indicator of cancer risk to man and serves as a guide to the need for preventive approaches involving improved means of waste disposal and environmental hygiene. Moreover, cancer in fish indicates that this important food source may be contaminated. Detection of genotoxic carcinogens to which fish are exposed can be achieved quickly and efficiently by carefully selected batteries of complementary in vitro and in vivo bioassays. One such battery consists of the Ames test, a reverse mutation assay in prokaryotic Salmonella typhimurium, and the Williams test, involving DNA repair in freshly explanted metabolically highly competent liver cells from diverse species, including humans. Determination of DNA-carcinogen adducts by varied techniques, including 32P-postlabeling, as well as DNA breakage, mammalian cell mutagenicity, chromosome aberrations, sister chromatid exchange, or cell transformation represent additional approaches, each with its own advantages and disadvantages. More research is needed on systems to apprehend neoplasm promoters, but tests to determine interruption of intercellular communications through gap junctions appear promising. Other approaches rely on measurement of enzymes such as ornithine decarboxylase and protein kinase C. Approaches to the definition of risk to fish or humans require characterization of the genotoxic or nongenotoxic properties of a chemical, relative potency data obtained in select, limited rodent bioassays, and knowledge of prevailing environmental concentrations of specific carcinogens.

  1. The Carcinogenic Agent Azoxymethane (AOM) Enhances Early Inflammation-induced Colon Crypt Pathology

    DEFF Research Database (Denmark)

    Venning, Freja Albjerg; Claesson, Mogens Helweg; Kissow, Hannelouise

    2013-01-01

    Severe combined immunodeficiency (SCID) mice transplanted with CD4+ T cells depleted of CD25+ regulatory T cells develop colitis within 2-3 weeks after the T cell transfer. In the present study we studied the effect of the carcinogen azoxymethane (AOM) on the colon crypt pathology of normal SCID...

  2. Modelling of carcinogenic effects resulting from the combined action of radon and smoking

    Energy Technology Data Exchange (ETDEWEB)

    Ryabova, S.V.; Petin, V.G. [Medical Radiological Research Centre, Obninsk (Russian Federation)

    2002-03-01

    A simple mathematical model designed for the description of cell survival [1] and later developed for the evaluation of mutagenic effects [2] was proposed for the optimisation of the determination and prognosis of levels of carcinogenic effects in organisms, resulting from the combined action of different agents. The model postulates that the occurrence of synergism is to be expected as a result of additional carcinogenic damage arising from the interaction of sublesions induced by the two agents under investigation. These molecular sublesions are suggested to be non-carcinogenic, if each agent is taken separately. The main conclusion pertaining to this model is the existence of the highest level of synergistic effect. The model predicts the input values and conditions under which this level is reached. The synergistic effect appeared to decline with any deviation from the optimal value for the ratio of carcinogenic effects produced by each agent alone. These conclusions were verified by comparison with experimental data published by other researchers. (orig.)

  3. Environmental Carcinogen Releases and Lung Cancer Mortality in Rural-Urban Areas of the United States

    Science.gov (United States)

    Luo, Juhua; Hendryx, Michael

    2011-01-01

    Purpose: Environmental hazards are unevenly distributed across communities and populations; however, little is known about the distribution of environmental carcinogenic pollutants and lung cancer risk across populations defined by race, sex, and rural-urban setting. Methods: We used the Toxics Release Inventory (TRI) database to conduct an…

  4. On the carcinogenic polycyclic aromatic hydrocarbon benzo(a)pyrene in volcano exhausts.

    Science.gov (United States)

    Ilnitsky, A P; Belitsky, G A; Shabad, L M

    1976-05-01

    The content of benzo(a)pyrene in the juvenile ashes of the volcano Tyatya (Kunashir Island, Kuriles) and in the soil, vegetation and volcanic mud collected near volcanos in Kamchatka was studied. It was concluded that volcanic activity does not play a large role in forming the background level of this carcinogen in the human environment.

  5. Mode of carcinogenic action of pesticides inducing thyroid follicular cell tumors in rodents.

    Science.gov (United States)

    Hurley, P M

    1998-08-01

    Of 240 pesticides screened for carcinogenicity by the U.S. Environmental Protection Agency Office of Pesticide Programs, at least 24 (10%) produce thyroid follicular cell tumors in rodents. Thirteen of the thyroid carcinogens also induce liver tumors, mainly in mice, and 9 chemicals produce tumors at other sites. Some mutagenic data are available on all 24 pesticides producing thyroid tumors. Mutagenicity does not seem to be a major determinant in thyroid carcinogenicity, except for possibly acetochlor; evidence is less convincing for ethylene thiourea and etridiazole. Studies on thyroid-pituitary functioning, including indications of thyroid cell growth and/or changes in thyroxine, triiodothyronine, or thyroid-stimulating hormone levels, are available on 19 pesticides. No such antithyroid information is available for etridiazole, N-octyl bicycloheptene dicarboximide, terbutryn, triadimefon, and trifluralin. Of the studied chemicals, only bromacil lacks antithyroid activity under study conditions. Intrathyroidal and extrathyroidal sites of action are found: amitrole, ethylene thiourea, and mancozeb are thyroid peroxidase inhibitors; and acetochlor, clofentezine, fenbuconazole, fipronil, pendimethalin, pentachloronitrobenzene, prodiamine, pyrimethanil, and thiazopyr seem to enhance the hepatic metabolism and excretion of thyroid hormone. Thus, with 12 pesticides that mode of action judgments can be made, 11 disrupt thyroid-pituitary homeostasis only; no chemical is mutagenic only; and acetochlor may have both antithyroid and some mutagenic activity. More information is needed to identify other potential antithyroid modes of thyroid carcinogenic action.

  6. To the application of the emission Mössbauer and positron annihilation spectroscopies for detection of carcinogens

    Science.gov (United States)

    Bokov, A. V.; Byakov, V. M.; Kulikov, L. A.; Perfiliev, Yu. D.; Stepanov, S. V.

    2017-11-01

    Being the main cause of cancer, almost all chemical carcinogens are strong electrophiles, that is, they have a high affinity for the electron. We have shown that positron annihilation lifetime spectroscopy (PALS) is able to detect chemical carcinogens by their inhibition of positronium (Ps) formation in liquid media. Electrophilic carcinogens intercept thermalized track electrons, which are precursors of Ps, and as a result, when they are present Ps atom does not practically form. Available biophysical data seemingly indicate that frozen solutions model better an intracellular medium than the liquid ones. So it is reasonable to use emission Mössbauer spectroscopy (EMS) to detect chemical carcinogens, measuring the yield of 57Fe2+ions formed in reactions of Auger electrons and other secondary electrons they produced with 57Fe3+. These reactions are similar to the Ps formation process in the terminal part the positron track: e++ e- =>Ps. So EMS and PALS are complementary methods for detection of carcinogenic compounds.

  7. Human bronchus-mediated mutagenesis of mammalian cells by carcinogenic polycyclic aromatic hydrocarbon

    DEFF Research Database (Denmark)

    Hsu, Ih Chang; Stoner, Gary D.; Autrup, Herman

    1978-01-01

    Cultured human bronchial explants activated benzo[alpha]pyrene (BzaP) into electrophilic metabolites that bind to DNA in bronchial epithelial cells. Promutagenic and mutagenic metabolites of BzaP were also released into the culture medium. An increase in mutation frequency for ouabain resistance ...

  8. Hepatitis B spliced protein (HBSP) promotes the carcinogenic effects of benzo [alpha] pyrene by interacting with microsomal epoxide hydrolase and enhancing its hydrolysis activity

    International Nuclear Information System (INIS)

    Chen, Jin-Yan; Chen, Wan-Nan; Jiao, Bo-Yan; Lin, Wan-Song; Wu, Yun-Li; Liu, Ling-Ling; Lin, Xu

    2014-01-01

    The risk of hepatocellular carcinoma (HCC) increases in chronic hepatitis B surface antigen (HBsAg) carriers who often have concomitant increase in the levels of benzo[alpha]pyrene-7,8-diol-9,10-epoxide(±) (BPDE)-DNA adduct in liver tissues, suggesting a possible co-carcinogenesis of Hepatitis B virus (HBV) and benzo[alpha]pyrene in HCC; however the exact mechanisms involved are unclear. The interaction between hepatitis B spliced protein (HBSP) and microsomal epoxide hydrolase (mEH) was confirmed using GST pull-down, co-immunoprecipitation and mammalian two-hybrid assay; the effects of HBSP on mEH-mediated B[alpha]P metabolism was examined by high performance liquid chromatography (HPLC); and the influences of HBSP on B[alpha]P carcinogenicity were evaluated by bromodeoxyuridine cell proliferation, anchorage-independent growth and tumor xenograft. HBSP could interact with mEH in vitro and in vivo, and this interaction was mediated by the N terminal 47 amino acid residues of HBSP. HBSP could greatly enhance the hydrolysis activity of mEH in cell-free mouse liver microsomes, thus accelerating the metabolism of benzo[alpha]pyrene to produce more ultimate carcinnogen, BPDE, and this effect of HBSP requires the intact HBSP molecule. Expression of HBSP significantly increased the formation of BPDE-DNA adduct in benzo[alpha]pyrene-treated Huh-7 hepatoma cells, and this enhancement was blocked by knockdown of mEH. HBSP could enhance the cell proliferation, accelerate the G1/S transition, and promote cell transformation and tumorigenesis of B[alpha]P-treated Huh-7 hepatoma cells. Our results demonstrated that HBSP could promote carcinogenic effects of B[alpha]P by interacting with mEH and enhancing its hydrolysis activity

  9. A study of tobacco carcinogenesis XLVIII. Carcinogenicity of N'-nitrosonornicotine in mink (Mustela vison).

    Science.gov (United States)

    Koppang, N; Rivenson, A; Reith, A; Dahle, H K; Evensen, O; Hoffmann, D

    1992-11-01

    During tobacco processing and smoking, nicotine and nornicotine give rise to N'-nitrosonornicotine (NNN), a highly abundant, strong carcinogen. NNN is known to exert carcinogenic activity in mice, rats and hamsters. Major target organs for NNN carcinogenicity in the rat are the esophagus and the nasal mucosa, and in the Syrian golden hamster trachea and nasal mucosa. In comparison with the rat, the mink (Mustela vison) has a markedly expanded nasal mucosa. Therefore, we explored in this study whether the mink could serve as a non-rodent model for nasal carcinogenesis using NNN as the carcinogen. Twenty random-bred mink, beginning at the age of 3 weeks, received twice weekly s.c. injections of NNN, a total dose of 11.9 mM per animal over a 38 week period. All of the 19 mink at risk developed malignant tumors of both the respiratory and the olfactory region of the nose within 3.5 years. In most animals the malignant tumors, primarily esthesioneuroepithelioma, invaded the brain. Remarkably, NNN induced no other tumors in the mink. None of the control animals developed nasal tumors nor tumors at other sites during the 3.5 years of the assay. The historical data from the farm did not reveal any spontaneous occurrence of nasal tumors in mink at any age. This study supports the concept that NNN is a proven carcinogen for multiple species of mammals and that the mink can serve as a non-rodent, non-inbred animal model for nasal carcinogenesis, especially since NNN induces only tumors in the nasal cavity in this species and not at other sites, as it does in mice, rats and hamsters.

  10. Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses

    International Nuclear Information System (INIS)

    Qi, Xiaozhe; Yu, Tao; Zhu, Liye; Gao, Jing; He, Xiaoyun; Huang, Kunlun; Luo, Yunbo; Xu, Wentao

    2014-01-01

    Ochratoxin A (OTA) has displayed nephrotoxicity and renal carcinogenicity in mammals, however, no clear mechanisms have been identified detailing the relationship between oxidative stress and these toxicities. This study was performed to clarify the relationship between oxidative stress and the renal carcinogenicity induced by OTA. Rats were treated with 70 or 210 μg/kg b.w. OTA for 4 or 13 weeks. In the rats administrated with OTA for 13 weeks, the kidney was damaged seriously. Cytoplasmic vacuolization was observed in the outer stripe of the outer medulla. Karyomegaly was prominent in the tubular epithelium. Kidney injury molecule-1 (Kim-1) was detected in the outer stripe of the outer medulla in both low- and high-dose groups. OTA increased the mRNA levels of clusterin in rat kidneys. Interestingly, OTA did not significantly alter the oxidative stress level in rat liver and kidney. Yet, some indications related to proliferation and carcinogenicity were observed. A dose-related increase in proliferating cell nuclear antigen (PCNA) was observed at 4 weeks in both liver and kidney, but at 13 weeks, only in the kidney. OTA down-regulated reactive oxygen species (ROS) and up-regulated vimentin and lipocalin 2 in rat kidney at 13 weeks. The p53 gene was decreased in both liver and kidney at 13 weeks. These results suggest that OTA caused apparent kidney damage within 13 weeks but exerted limited effect on oxidative stress parameters. It implies that cell proliferation is the proposed mode of action for OTA-induced renal carcinogenicity. - Highlights: • We studied OTA toxicities in both the rat liver and kidney for 13 weeks. • OTA exerts limited effects on oxidative stress in the rat liver and kidney. • OTA induced renal carcinogenicity resulting from cell proliferation

  11. Effect of chemical mutagens and carcinogens on gene expression profiles in human TK6 cells.

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    Lode Godderis

    Full Text Available Characterization of toxicogenomic signatures of carcinogen exposure holds significant promise for mechanistic and predictive toxicology. In vitro transcriptomic studies allow the comparison of the response to chemicals with diverse mode of actions under controlled experimental conditions. We conducted an in vitro study in TK6 cells to characterize gene expression signatures of exposure to 15 genotoxic carcinogens frequently used in European industries. We also examined the dose-responsive changes in gene expression, and perturbation of biochemical pathways in response to these carcinogens. TK6 cells were exposed at 3 dose levels for 24 h with and without S9 human metabolic mix. Since S9 had an impact on gene expression (885 genes, we analyzed the gene expression data from cells cultures incubated with S9 and without S9 independently. The ribosome pathway was affected by all chemical-dose combinations. However in general, no similar gene expression was observed among carcinogens. Further, pathways, i.e. cell cycle, DNA repair mechanisms, RNA degradation, that were common within sets of chemical-dose combination were suggested by clustergram. Linear trends in dose-response of gene expression were observed for Trichloroethylene, Benz[a]anthracene, Epichlorohydrin, Benzene, and Hydroquinone. The significantly altered genes were involved in the regulation of (anti- apoptosis, maintenance of cell survival, tumor necrosis factor-related pathways and immune response, in agreement with several other studies. Similarly in S9+ cultures, Benz[a]pyrene, Styrene and Trichloroethylene each modified over 1000 genes at high concentrations. Our findings expand our understanding of the transcriptomic response to genotoxic carcinogens, revealing the alteration of diverse sets of genes and pathways involved in cellular homeostasis and cell cycle control.

  12. Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses

    Energy Technology Data Exchange (ETDEWEB)

    Qi, Xiaozhe; Yu, Tao; Zhu, Liye; Gao, Jing [College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); He, Xiaoyun; Huang, Kunlun; Luo, Yunbo [College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Xu, Wentao, E-mail: xuwentao@cau.edu.cn [College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China)

    2014-11-01

    Ochratoxin A (OTA) has displayed nephrotoxicity and renal carcinogenicity in mammals, however, no clear mechanisms have been identified detailing the relationship between oxidative stress and these toxicities. This study was performed to clarify the relationship between oxidative stress and the renal carcinogenicity induced by OTA. Rats were treated with 70 or 210 μg/kg b.w. OTA for 4 or 13 weeks. In the rats administrated with OTA for 13 weeks, the kidney was damaged seriously. Cytoplasmic vacuolization was observed in the outer stripe of the outer medulla. Karyomegaly was prominent in the tubular epithelium. Kidney injury molecule-1 (Kim-1) was detected in the outer stripe of the outer medulla in both low- and high-dose groups. OTA increased the mRNA levels of clusterin in rat kidneys. Interestingly, OTA did not significantly alter the oxidative stress level in rat liver and kidney. Yet, some indications related to proliferation and carcinogenicity were observed. A dose-related increase in proliferating cell nuclear antigen (PCNA) was observed at 4 weeks in both liver and kidney, but at 13 weeks, only in the kidney. OTA down-regulated reactive oxygen species (ROS) and up-regulated vimentin and lipocalin 2 in rat kidney at 13 weeks. The p53 gene was decreased in both liver and kidney at 13 weeks. These results suggest that OTA caused apparent kidney damage within 13 weeks but exerted limited effect on oxidative stress parameters. It implies that cell proliferation is the proposed mode of action for OTA-induced renal carcinogenicity. - Highlights: • We studied OTA toxicities in both the rat liver and kidney for 13 weeks. • OTA exerts limited effects on oxidative stress in the rat liver and kidney. • OTA induced renal carcinogenicity resulting from cell proliferation.

  13. Detecting Beer Intake by Unique Metabolite Patterns.

    Science.gov (United States)

    Gürdeniz, Gözde; Jensen, Morten Georg; Meier, Sebastian; Bech, Lene; Lund, Erik; Dragsted, Lars Ove

    2016-12-02

    Evaluation of the health related effects of beer intake is hampered by the lack of accurate tools for assessing intakes (biomarkers). Therefore, we identified plasma and urine metabolites associated with recent beer intake by untargeted metabolomics and established a characteristic metabolite pattern representing raw materials and beer production as a qualitative biomarker of beer intake. In a randomized, crossover, single-blinded meal study (MSt1), 18 participants were given, one at a time, four different test beverages: strong, regular, and nonalcoholic beers and a soft drink. Four participants were assigned to have two additional beers (MSt2). In addition to plasma and urine samples, test beverages, wort, and hops extract were analyzed by UPLC-QTOF. A unique metabolite pattern reflecting beer metabolome, including metabolites derived from beer raw material (i.e., N-methyl tyramine sulfate and the sum of iso-α-acids and tricyclohumols) and the production process (i.e., pyro-glutamyl proline and 2-ethyl malate), was selected to establish a compliance biomarker model for detection of beer intake based on MSt1. The model predicted the MSt2 samples collected before and up to 12 h after beer intake correctly (AUC = 1). A biomarker model including four metabolites representing both beer raw materials and production steps provided a specific and accurate tool for measurement of beer consumption.

  14. Plant metabolites and nutritional quality of vegetables.

    Science.gov (United States)

    Hounsome, N; Hounsome, B; Tomos, D; Edwards-Jones, G

    2008-05-01

    Vegetables are an important part of the human diet and a major source of biologically active substances such as vitamins, dietary fiber, antioxidants, and cholesterol-lowering compounds. Despite a large amount of information on this topic, the nutritional quality of vegetables has not been defined. Historically, the value of many plant nutrients and health-promoting compounds was discovered by trial and error. By the turn of the century, the application of chromatography, mass spectrometry, infrared spectrometry, and nuclear magnetic resonance allowed quantitative and qualitative measurements of a large number of plant metabolites. Approximately 50000 metabolites have been elucidated in plants, and it is predicted that the final number will exceed 200000. Most of them have unknown function. Metabolites such as carbohydrates, organic and amino acids, vitamins, hormones, flavonoids, phenolics, and glucosinolates are essential for plant growth, development, stress adaptation, and defense. Besides the importance for the plant itself, such metabolites determine the nutritional quality of food, color, taste, smell, antioxidative, anticarcinogenic, antihypertension, anti-inflammatory, antimicrobial, immunostimulating, and cholesterol-lowering properties. This review is focused on major plant metabolites that characterize the nutritional quality of vegetables, and methods of their analysis.

  15. Secondary metabolites in fungus-plant interactions

    Science.gov (United States)

    Pusztahelyi, Tünde; Holb, Imre J.; Pócsi, István

    2015-01-01

    Fungi and plants are rich sources of thousands of secondary metabolites. The genetically coded possibilities for secondary metabolite production, the stimuli of the production, and the special phytotoxins basically determine the microscopic fungi-host plant interactions and the pathogenic lifestyle of fungi. The review introduces plant secondary metabolites usually with antifungal effect as well as the importance of signaling molecules in induced systemic resistance and systemic acquired resistance processes. The review also concerns the mimicking of plant effector molecules like auxins, gibberellins and abscisic acid by fungal secondary metabolites that modulate plant growth or even can subvert the plant defense responses such as programmed cell death to gain nutrients for fungal growth and colonization. It also looks through the special secondary metabolite production and host selective toxins of some significant fungal pathogens and the plant response in form of phytoalexin production. New results coming from genome and transcriptional analyses in context of selected fungal pathogens and their hosts are also discussed. PMID:26300892

  16. Functional metabolite assemblies—a review

    Science.gov (United States)

    Aizen, Ruth; Tao, Kai; Rencus-Lazar, Sigal; Gazit, Ehud

    2018-05-01

    Metabolites are essential for the normal operation of cells and fulfill various physiological functions. It was recently found that in several metabolic disorders, the associated metabolites could self-assemble to generate amyloid-like structures, similar to canonical protein amyloids that have a role in neurodegenerative disorders. Yet, assemblies with typical amyloid characteristics are also known to have physiological function. In addition, many non-natural proteins and peptides presenting amyloidal properties have been used for the fabrication of functional nanomaterials. Similarly, functional metabolite assemblies are also found in nature, demonstrating various physiological roles. A notable example is the structural color formed by guanine crystals or fluorescent crystals in feline eyes responsible for enhanced night vision. Moreover, some metabolites have been used for the in vitro fabrication of functional materials, such as glycine crystals presenting remarkable piezoelectric properties or indigo films used to assemble organic semi-conductive electronic devices. Therefore, we believe that the study of metabolite assemblies is not only important in order to understand their role in normal physiology and in pathology, but also paves a new route in exploring the fabrication of organic, bio-compatible materials.

  17. Pharmaceutically active secondary metabolites of marine actinobacteria.

    Science.gov (United States)

    Manivasagan, Panchanathan; Venkatesan, Jayachandran; Sivakumar, Kannan; Kim, Se-Kwon

    2014-04-01

    Marine actinobacteria are one of the most efficient groups of secondary metabolite producers and are very important from an industrial point of view. Many representatives of the order Actinomycetales are prolific producers of thousands of biologically active secondary metabolites. Actinobacteria from terrestrial sources have been studied and screened since the 1950s, for many important antibiotics, anticancer, antitumor and immunosuppressive agents. However, frequent rediscovery of the same compounds from the terrestrial actinobacteria has made them less attractive for screening programs in the recent years. At the same time, actinobacteria isolated from the marine environment have currently received considerable attention due to the structural diversity and unique biological activities of their secondary metabolites. They are efficient producers of new secondary metabolites that show a range of biological activities including antibacterial, antifungal, anticancer, antitumor, cytotoxic, cytostatic, anti-inflammatory, anti-parasitic, anti-malaria, antiviral, antioxidant, anti-angiogenesis, etc. In this review, an evaluation is made on the current status of research on marine actinobacteria yielding pharmaceutically active secondary metabolites. Bioactive compounds from marine actinobacteria possess distinct chemical structures that may form the basis for synthesis of new drugs that could be used to combat resistant pathogens. With the increasing advancement in science and technology, there would be a greater demand for new bioactive compounds synthesized by actinobacteria from various marine sources in future. Copyright © 2013 Elsevier GmbH. All rights reserved.

  18. TRANSCRIPTOMIC ANALYSIS OF F344 RAT NASAL EPITHELIUM SUGGESTS THAT THE LACK OF CARCINOGENIC RESPONSE TO GLUTARALDEHYDE IS DUE TO ITS GREATER TOXICITY COMPARED TO FORMALDEHYDE

    Science.gov (United States)

    Formaldehyde is cytotoxic and carcinogenic to the rat nasal respiratory epithelium inducing tumors after 12 months. Glutaraldehyde is also cytotoxic but is not carcinogenic to nasal epithelium even after 24 months. Both aldehydes induce similar acute and subchronic histopathology...

  19. Ultimate uniaxial compressive strength of stiffened panel with opening under lateral pressure

    Directory of Open Access Journals (Sweden)

    Chang-Li Yu

    2015-03-01

    Full Text Available This paper concentrated on the ultimate uniaxial compressive strength of stiffened panel with opening under lateral load and also studied the design-oriented formulae. For this purpose, three series of well executed experiments on longitudinal stiffened panel with rectangular opening subjected to the combined load have been selected as test models. The finite element analysis package, ABAQUS, is used for simulation with considering the large elasticplastic deflection behavior of stiffened panels. The feasibility of the numerical procedure is verified by a good agreement of experimental results and numerical results. More cases studies are executed employing nonlinear finite element method to analyze the influence of design variables on the ultimate strength of stiffened panel with opening under combined pressure. Based on data, two design formulae corresponding to different opening types are fitted, and accuracy of them is illustrated to demonstrate that they could be applied to basic design of practical engineering structure.

  20. The Assessment of the Ultimate Hull Girder Strength of RO-RO Ship after Damages

    Science.gov (United States)

    Zubair Muis Alie, Muhammad; Sitepu, Ganding; Izaak Latumahin, Samuel

    2018-03-01

    Many accidents of Ro-Ro ships happen in Indonesia such as collision and grounding. When the collision or grounding takes place on the Ro-Ro ship, the ultimate strength of hull structure after damage becomes decrease. Car and passenger decks are critical location since collision and/or grounding occur. In the present study, the assessment of the ultimate hull girder strength is conducted. The cross section of Ro-Ro ship is taken to be analyzed. The collision and grounding damages are assumed to be palced on the side and bottom area, respectively. The damages are created by removing the element from the side shell and bottom part. Finally, the result obtained is compared with one another.