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Potent Carcinogen (potent + carcinogen)

Distribution by Scientific Domains

Chemistry	50%
Life Sciences	33%

Selected Abstracts

Molecular responses of Campylobacter jejuni to cadmium stress

FEBS JOURNAL, Issue 20 2008
Nadeem O. Kaakoush
Cadmium ions are a potent carcinogen in animals, and cadmium is a toxic metal of significant environmental importance for humans. Response curves were used to investigate the effects of cadmium chloride on the growth of Camplyobacter jejuni. In vitro, the bacterium showed reduced growth in the presence of 0.1 mm cadmium chloride, and the metal ions were lethal at 1 mm concentration. Two-dimensional gel electrophoresis combined with tandem mass spectrometry analysis enabled identification of 67 proteins differentially expressed in cells grown without and with 0.1 mm cadmium chloride. Cellular processes and pathways regulated under cadmium stress included fatty acid biosynthesis, protein biosynthesis, chemotaxis and mobility, the tricarboxylic acid cycle, protein modification, redox processes and the heat-shock response. Disulfide reductases and their substrates play many roles in cellular processes, including protection against reactive oxygen species and detoxification of xenobiotics, such as cadmium. The effects of cadmium on thioredoxin reductase and disulfide reductases using glutathione as a substrate were studied in bacterial lysates by spectrophotometry and nuclear magnetic resonance spectroscopy, respectively. The presence of 0.1 mm cadmium ions modulated the activities of both enzymes. The interactions of cadmium ions with oxidized glutathione and reduced glutathione were investigated using nuclear magnetic resonance spectroscopy. The data suggested that, unlike other organisms, C. jejuni downregulates thioredoxin reductase and upregulates other disulfide reductases involved in metal detoxification in the presence of cadmium. [source]

Impact of estragole and other odorants on the flavour of anise and tarragon

FLAVOUR AND FRAGRANCE JOURNAL, Issue 2 2007
Annette Zeller
Abstract Since estragole has been described as potent carcinogen and did not show any flavour impact on the odour of fennel, the flavour of anise and tarragon was examined by combinations of instrumental and sensory analyses. In anise fruits, trans- anethole, 2-isopropyl-3-methoxypyrazine, and anisaldehyde showed high flavour dilution (FD) factors, followed by those of eugenol, cis- anethole, estragole and linalool. Quantitation of the odorants showing higher FD factors in anise tea, and calculation of odour activity values (OAVs) by dividing the concentrations of the respective compound by its recognition threshold in water revealed the highest OAV for trans- anethole, followed by those of anisaldehyde and estragole. Still, an aroma impact of estragole next to trans- anethole could be neglected, due to former sensory studies of aqueous models of fennel tea. For tarragon, AEDA revealed the highest FD factors for eugenol, 7-methoxycoumarin, , -ionone, 2-isopropyl-3-methoxypyrazine, estragole and linalool. Of these, estragole and 7-methoxycoumarine were most abundant in tarragon leaves, showing contents of 2900 and 220 mg/kg, respectively. To calculate OAVs, the contents of potent odorants were divided by their odour threshold in starch or cellulose, as these were the main constituents of the leaves. In this way, , -ionone and eugenol showed the highest OAVs of 5862 and 2653, repectively, followed by estragole (OAV = 460), cis- 1,5-octadiene-3-one (OAV = 140), vanilline (OAV = 139) and 2-isopropyl-3-methoxypyrazine (OAV = 130). Therefore, it was concluded that , -ionone and eugenol made the greatest contribution to the overall flavour of tarragon, whereas estragole and the other odorants were of minor importance. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Dothistroma (red-band) needle blight of pines and the dothistromin toxin: a review

FOREST PATHOLOGY, Issue 3 2004
R. E. Bradshaw
Summary Dothistroma (red-band) needle blight has been a problem in plantations of exotic pines in the southern hemisphere for many decades. The prevalence of this disease is currently increasing in the northern hemisphere and is now affecting trees in their native ranges. The fungal pathogen Mycosphaerella pini with its anamorph Dothistroma pini, which is responsible for the disease, produces a toxin, dothistromin, that is closely related to the potent carcinogen, aflatoxin. Understandably this has provoked concern about possible effects on the health of forestry workers. This review gives a broad coverage of literature on both disease and toxin. The fungus has a complicated taxonomy with many synonyms and in most countries only the anamorph is found. It is a necrotrophic pathogen that kills needle tissue and completes its life cycle in the lesion thus formed. Dispersal of the disease is normally by rain splash of conidiospores but there is evidence that long range dispersal has occurred by transport of contaminated plant tissue and by wind/cloud dispersal of spores in air currents. The severity of disease is affected by humidity, temperature and light. There is variation in susceptibility of different Pinus species and some achieve increased resistance with age. The current method of control in southern hemisphere plantation forests is through spraying with copper fungicides and, with P. radiata, increased disease resistance has been achieved through a breeding programme. The dothistromin toxin is a difuroanthraquinone and is similar in structure to the aflatoxin precursor versicolorin B. Part of a gene cluster encoding dothistromin biosynthetic genes has been cloned and this has confirmed parallels between the dothistromin and aflatoxin biosynthetic pathways. Dothistromin produces damaging oxygen radicals by reductive oxygen activation rather than by photosensitization, but is also thought to exert its toxic effects on specific cellular targets. Studies have shown that dothistromin is a weak mutagen and clastogen and is therefore a potential carcinogen. Although the risks to forest workers are considered very low it is prudent to avoid unnecessary exposure during periods when dothistromin levels are likely to be at their peak. Résumé La maladie des bandes rouges causée par Dothistroma est un problème dans les plantations de pins exotiques de l'hémisphère sud depuis de nombreuses années. La prévalence de cette maladie est en augmentation dans l'hémisphère nord et affecte maintenant les pins dans leurs régions d'origine. Le champignon pathogène Dothistroma pini, responsable de la maladie, produit une toxine, la dothistromine, proche de l'aflatoxine qui est un puissant carcinogène. Ceci pose donc la question des effets possibles sur la santé des travailleurs forestiers. Cette revue repose sur une large couverture de la littérature concernant aussi bien la maladie que la toxine. Le champignon a une taxonomie complexe avec de nombreux synonymes, et seul l'anamorphe se rencontre dans de nombreux pays. C'est un champignon nécrotrophe qui tue les tissus de l'aiguille et réalise son cycle biologique dans la lésion ainsi formée. La dissémination de la maladie s'effectue principalement par éclaboussures de pluie contenant les conidies mais une dissémination à longue distance a été mise en évidence par transport de matériel contaminé ou par dissémination des spores par le vent ou les nuages dans les courants aériens. La sévérité de la maladie est affectée par l'humidité, la température et la lumière. Il existe des différences de sensibilité entre espèces de Pinus, et certaines présentent une résistance accrue avec l'âge. La méthode actuelle de lutte dans les forêts de plantations de l'hémisphère sud consiste à pulvériser des fongicides à base de cuivre ; dans le cas de Pinus radiata, une augmentation de la résistance a été obtenue grâce à un programme d'amélioration génétique. La toxine dothistromine est une difuroanthraquinone, similaire en structure à la versicolorine B, précurseur de l'aflatoxine. Une partie d'une batterie de gènes comprenant des gènes de biosynthèse de la dothistromine a été clonée, confirmant les analogies entre les voies de biosynthèse de la dothistromine et de l'aflatoxine. La dothistromine produit des radicaux oxygène nocifs par activation de la réduction de l'oxygène plutôt que par photosensibilisation, mais ses effets toxiques s'exercent aussi probablement sur des sites cellulaires spécifiques. Des études montrent que la dothistromine est un mutagène et clastogène faible, et donc potentiellement carcinogène. Bien que les risques pour les ouvriers forestiers soient considérés comme très faibles, il est prudent d'éviter dans la mesure du possible de s'exposer dans les périodes où les niveaux de dothistromine sont supposés élevés. Zusammenfassung Die Dothistroma -Nadelbräune ist in der Südhemisphäre in Plantagen mit exotischen Kiefernarten seit vielen Jahren ein Problem. In der Nordhemisphäre nimmt die Bedeutung dieser Krankheit derzeit zu und sie befällt nun Bäume auch in ihren natürlichen Verbreitungsgebieten. Der Erreger ist der Ascomycet Mycosphaerella pini (Anamorphe: Dothistroma pini). Der Pilz bildet das Toxin Dothistromin, das eng mit dem hochtoxischen Karzinogen Aflatoxin verwandt ist. Daraus ergab sich die Frage nach möglichen Nebenwirkungen dieser Baumkrankheit auf die Gesundheit von Waldarbeitern. Dieser Review fasst die Information über die Krankheit und das Toxin zusammen. Der Pilz hat eine komplizierte Taxonomie mit vielen Synonymen und in den meisten Ländern wurde nur die Anamorphe nachgewiesen. Er ist ein nekrotrophes Pathogen, das Blattgewebe abtötet, und in den so gebildeten Läsionen seinen Lebenszyklus abschliesst. Der normale Ausbreitungsweg der Krankheit erfolgt über Konidiosporen mit Regentropfen, aber es gibt auch Hinweise auf einen Ferntransport mit infiziertem Pflanzenmaterial und über die Verbreitung von Sporen mit dem Wind bzw. Wolken in Luftströmungen. Die Krankheitsintensität wird durch Luftfeuchte, Temperatur und Licht beeinflusst. Es gibt Unterschiede in der Anfälligkeit zwischen verschiedenen Kiefernarten und manche davon werden mit zunehmendem Alter resistenter. Derzeit werden in Plantagen der südlichen Hemisphäre Kupferfungizide zur Kontrolle dieser Krankheit eingesetzt und für Pinus radiata wurde in Züchtungsprogrammen eine erhöhte Resistenz erreicht. Das Toxin Dothistromin ist ein Difuroanthrachinon und ähnelt in seiner Struktur dem Aflatoxin-Präkursor Versicolorin B. Ein Teil des Genclusters, das die Dothistromin-Biosynthese codiert, wurde geklont, und es wurden dabei Parallelen zwischen dem Dothistromin- und dem Aflatoxin-Biosyntheseweg bestätigt. Dothistromin bildet schädliche Sauerstoffradikale (wahrscheinlich eher durch reduktive Sauerstoffaktivierung als durch Photosensibilisierung), es dürfte aber auch auf spezifische Zellkomponenten toxisch wirken. Dothistromin zeigt schwache mutagene und chromosomenschädigende Wirkungen und ist deshalb ein potentielles Karzinogen. Obwohl das Risiko für Waldarbeiter als gering eingeschätzt wird, sollte man in Perioden, in denen der Dothistromingehalt hoch sein dürfte, eine unnötige Exposition vermeiden. [source]

From Dioxin to Drug Lead,The Development of 2,3,7,8-Tetrachlorophenothiazine

CHEMMEDCHEM, Issue 6 2007
Kristian
Abstract Polychlorinated dibenzo-p-dioxins are persistent environmental pollutants. The most potent congener, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), causes a wasting syndrome and is a potent carcinogen and immunosuppressant in the rat at high doses. However, low doses cause opposite effects to some of those observed at higher doses, resulting in chemoprevention, stimulation of the immune system, and longevity in experimental animals. The new TCDD analogue, 2,3,7,8-tetrachlorophenothiazine (TCPT), was developed to take advantage of the low-dose effects of dioxins that have potential application as therapeutics. Its development marked a deviation from the traditional scope of phenothiazine drug design by deriving biological effects from aryl substituents. TCPT was synthesized in three steps. The key ring-closing step was performed utilizing a Buchwald-Hartwig amination to provide TCPT in 37,% yield. Its potency to induce CYP1A1 activity over 24,h was 370 times lower than that of TCDD in,vitro. The elimination half-life of the parent compound in serum was 5.4,h in the rat and 2.7,h in the guinea pig, compared to 11 and 30 days, respectively, for TCDD. These initial findings clearly differentiate TCPT from TCDD and provide the basis for further studies of its potential as a drug lead. [source]

Recombination and lineage-specific gene loss in the aflatoxin gene cluster of Aspergillus flavus

MOLECULAR ECOLOGY, Issue 23 2009
GEROMY G. MOORE
Abstract Aflatoxins produced by Aspergillus flavus are potent carcinogens that contaminate agricultural crops. Recent efforts to reduce aflatoxin concentrations in crops have focused on biological control using nonaflatoxigenic A. flavus strains AF36 (=NRRL 18543) and NRRL 21882 (the active component of afla-guard®). However, the evolutionary potential of these strains to remain nonaflatoxigenic in nature is unknown. To elucidate the underlying population processes that influence aflatoxigenicity, we examined patterns of linkage disequilibrium (LD) spanning 21 regions in the aflatoxin gene cluster of A. flavus. We show that recombination events are unevenly distributed across the cluster in A. flavus. Six distinct LD blocks separate late pathway genes aflE, aflM, aflN, aflG, aflL, aflI and aflO, and there is no discernable evidence of recombination among early pathway genes aflA, aflB, aflC, aflD, aflR and aflS. The discordance in phylogenies inferred for the aflW/aflX intergenic region and two noncluster regions, tryptophan synthase and acetamidase, is indicative of trans-species evolution in the cluster. Additionally, polymorphisms in aflW/aflX divide A. flavus strains into two distinct clades, each harbouring only one of the two approved biocontrol strains. The clade with AF36 includes both aflatoxigenic and nonaflatoxigenic strains, whereas the clade with NRRL 21882 comprises only nonaflatoxigenic strains and includes all strains of A. flavus missing the entire gene cluster or with partial gene clusters. Our detection of LD blocks in partial clusters indicates that recombination may have played an important role in cluster disassembly, and multilocus coalescent analyses of cluster and noncluster regions indicate lineage-specific gene loss in A. flavus. These results have important implications in assessing the stability of biocontrol strains in nature. [source]

The determination of N- nitrosamines in food

QUALITY ASSURANCE & SAFETY OF CROPS & FOOD, Issue 1 2010
Colin Crews
Abstract Introduction N -nitrosamines are formed in food as a result of natural chemical interactions, but mainly through food processing activity. Most are potent carcinogens and their determination is therefore of considerable importance. They exist in various chemical forms and have been measured by colorimetric and spectroscopic methods following gas or liquid chromatography or as a total N -nitroso group by measurement of chemically released nitric oxide. Objectives To provide an overview of the available methods for the analysis of N -nitrosamines in food that includes recently developments. Methods The literature was reviewed from the discovery of the N -nitrosamine problem and the introduction on the N -nitroso-specific detector. Results The evaluation shows that analytical detection methods for volatile N -nitrosamines in food have changed little since the introduction on the N -nitroso-specific detector and that research into the occurrence and formation of both non-volatile N -nitrosamines and the apparent total N -nitroso content (ATNC) have declined. Methods for measuring the apparent total N -nitroso content have not been improved significantly in recent years. Conclusion Modern sample extraction techniques and mass spectrometric methods for the volatile N -nitrosamines have been applied more extensively to water analysis and offer a good opportunity to improve the determination of these carcinogens in food and make the analysis more widely available. Developments in liquid chromatography-mass spectrometry should provide an avenue for renewed interest in non-volatile N -nitrosamines, and could help with the identification of novel compounds whose presence is suggested by the high apparent total N -nitroso content of some foods. [source]