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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 46 (1968), S. 1117-1120 
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0738
    Keywords: Carcinogenesis ; Genotoxicity ; Wood dust constituents ; Beech wood ; Micronucleus ; DNA damage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Human exposure to wood dust has been epidemiologically linked to a number of enhanced incidences of various neoplasias, including those of the nose. Among different suspected woods, long-term exposure to the dust of beech (Fagus silvatica) is strongly associated with development of these tumors. Experimentally, it has been shown that a simple alcoholic extract of beech wood dust is mutagenic toward some bacteria and tumorigenic on mouse skin. For the present study, different groups of male Wistar rats were treated with aqueous, ethanol, or methanol extract of untreated beech wood dust via nasal drip at three concentrations for 48 h. Animals were killed 24 h after the last treatment and the nasal tissues were isolated to be examined for possible induction of micronuclei and DNA adducts. A clear dose-dependent increase in the number of micronuclei (P〈0.01) was observed after treatment of rats with each alcoholic extract of wood dust. In contrast, no DNA adducts could be detected with these extracts using the32P-postlabelling technique. No increased number of micronucleated cells was found with solvents alone or with aqueous extract of dust. These data might support the early hypothesis that wood dust per se contains some in vivo genotoxic and thus possibly carcinogenic components extractable by an alcohol.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1335
    Keywords: Tobacco smoke condensate ; Mainstream smoke ; Sidestream smoke ; Passive smoking ; Mouse skin tumorigenicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The direct carcinogenic effects of sidestream (SS) and mainstream (MS) smoke condensates of a filtered commercial brand of blond cigarettes were compared using a lifetime mouse skin tumorigenicity assay on female NMRI mice. Each cigarette was smoked by a smoking machine under the standard conditions, and the separately collected SS and MS smoke condensates were extracted with acetone/methanol as described elsewhere. These were tested for carcinogenicity on an area of 1–1.5 cm shaved skin of mice on the lower back. The mice were treated with half of each dose (5, 10 or 15 mg) twice a week, for only 3 months. No substance was used as promoter or as an additional initiator of carcinogenicity. No statistically significant difference was found when the life spans of MS-treated and untreated animals were compared. In contrast, the life spans of SS-treated mice were significantly (P〈0.01) shorter than those of MS-treated animals or those of all three negative control groups together. The observed carcinogenic effects were based on tumours and lesions found only on the site of application of the test material. Of 210 mice (effective number, 129) serving as the negative controls, 3 developed skin lesions but no tumours. Of 210 MS-treated mice (effective number, 177), 7 developed tumours (4 malignant and 3 benign) and 35 had a uniform type of precancerous skin lesions. The numbers of tumours or lesions were not increased dose-dependently. Of 210 SS-treated animals (effective number, 182), 30 developed tumours (16 malignant and 14 benign) and 56 had a uniform type of precancerous skin lesion. The initiation of these latter lesions was found to be dose-dependent (P〈0.001).The SS-treated animals developed two to six times more skin tumours than the MS-treated mice. Comparing the negative controls with the MS- or SS-treated animals, the overall carcinogenic effect observed was statistically significant. Comparing the MS- with SS-treated animals, the overall carcinogenic effect of SS was much higher than that of MS (P〈0.001).
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1335
    Keywords: Key words Lung cancer ; p53 ; Codon 213 polymorphism ; Radon ; Uranium mining
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: There is a high prevalence of G→T transversions of p53 in lung cancers of smokers. One study has reported a special “hotspot” mutation at codon 249 of p53 in lung cancers of former uranium miners. The aim of our study was to look for mutational spectra of p53 in former German uranium miners with lung cancers. Methods: We investigated 16 patients with lung cancer who had worked as uranium miners in Germany and 13 lung cancer patients without a mining history of the same region. By means of the polymerase chain reaction and sequencing we looked for mutations in exons 5–7 of the p53 gene. Results: We could not find any suggestion of hotspot mutations. The only G→T mutation in former uranium miners was detected in the only nonsmoker. In 3 patients (19% of the total) we found a codon 213/3 polymorphism. Conclusions: The results indicate that G → T transversions do not seem to be very common mutations in p53 in lung cancers probably caused by radiation. Therefore, p53 may be mutated early in lung cancer development if radiation exposure is a critical factor in carcinogenesis. In accordance with studies of thyroid cancer patients in the Chernobyl region, our results may indicate an overrepresentation of codon 213/3 polymorphism in p53 in radiation-caused cancers.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    International archives of occupational and environmental health 50 (1982), S. 187-196 
    ISSN: 1432-1246
    Keywords: Vinylchlorid (VCM) ; Vinylchlorid-Metabolismus ; Thiodiglykolsäure ; „Biolocigal monitoring” ; Vinyl chloride (VCM) ; Vinyl chloride metabolism ; Thiodiglycolic acid ; Biological monitoring
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Fifteen workers employed in a PVC producing plant were investigated concerning their individual vinyl chloride (VCM) exposure and the urinary excretion of the VCM metabolite thiodiglycolic acid (TdGA). The urine concentrations found were in the range 0.94–20.4 μg/ml. These could be compared with exposure data calculated from VCM air analyses performed by personal air sampling and corrected with respect to the exposure times of the workers. The amounts of TdGA excreted within 24 h were correlated with the effective VCM body concentrations calculated from the exposure data as mean values for 12 h periods (Spearman coefficient P=α〈0.005). This correlation resembles a function of the Michaelis-Menten type. It could be shown that during short exposure periods of less than 5 min, the metabolite formation in relation to the exposure data was lower than during longer periods of exposure although, as would be expected, there were some fluctuations of the exposure level. Therefore, the VCM body concentrations could not normally reach steady state values.
    Notes: Zusammenfassung In einer Feldstudie an 15 Beschäftigten eines PVC-produzierenden Betriebes wurde der Zusammenhang zwischen der Höhe der Exposition gegenüber monomerem Vinylchlorid (VCM) und der Ausscheidung des VCM-Harnmetaboliten Thiodiglykolsäure (TdGA) untersucht. Die ermittelten Harnkonzentrationen, die sich zwischen 0,94 und 20,4 μg/ml bewegten, konnten mit Expositionsdaten verglichen werden, die durch „personal air sampling” unter Berücksichtigung der Aufenthaltszeiten im Expositionsbereich gewonnen werden waren. Aus den mit Personendosimetern gewonnenen Analysedaten wurden unter Berücksichtigung pharmakokinetischer Gesetzmäßigkeiten die effektiven VCM-Körperkonzentrationen als 12-h-Mittelwerte kalkuliert. Mit diesen waren die im 24-h-Harn ausgeschiedenen Mengen an TdGA deutlich korreliert (P=α〈0,005; Spearman-Koeffizient). Die Korrelation entspricht in guter Näherung einer Funktion vom Michaelis-Mengen-Typ. Unter Berücksichtigung der Arbeitsprotokolle konnte aus den Meßdaten abgeleitet werden, daß bei Ansteigen der VCM-Luftkonzentration für Zeiträume von weniger als 5 min die Metabolitenausscheidung relativ zur kalkulierten mittleren Körper-konzentration geringer ansteigt als bei längerfristigen Expositions schwankungen. Offenbar schwankte die VCM-Raumluftkonzentration derart, daß die VCM-Körperkonzentrationen den Gleichgewichtswert in der Regel nicht erreichten.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1246
    Keywords: Aromatic amines ; Urine concentrations Hemoglobin adducts ; Exposed workers ; Smoking habits
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The renal excretion of arylamines in occupationally exposed and nonexposed subjects was measured by a gas chromatography-electron capture detector method. Additionally, in the occupationally exposed persons hemoglobin adduct levels of arylamines were determined by a liquid chromatography-electrochemical detector method, together with the individual acetylator status. The aromatic amines aniline,p-toluidine, 2-naphthylamine, and 4-chloro-o-toluidine were detected in the urine of nonsmoking subjects who were not occupationally exposed to arylamines. Significantly higher concentrations of aniline,o-toluidine,m-toluidine, 2-naphthylamine, and 4-methyl-1,3-phenylenediamine could be observed in the urine of smoking control persons in comparison to nonsmokers. Comparison of smokers and nonsmokers in a group of workers primarily exposed to aniline and 4-chloroaniline revealed significant differences (P 〈 0.05) in the formation of 4-aminodiphenyl hemoglobin adducts and in the renal excretion of 2-naphthylamine. The slow acetylators in this group produced significantly more hemoglobin adducts of aniline and 4-chloroaniline than did the fast acetylators. In slow acetylators among the smoking workers there was a significant increase in the formation of 4-aminodiphenyl hemoglobin adducts and in the renal excretion of 4-chloroaniline andm-toluidine. The results indicate that there are influences of smoking habits and acetylator status on the levels of arylamine hemoglobin adducts as well as urinary arylamine concentrations. Hemoglobin adducts seem to be good parameters for monitoring aniline and 4-chloroaniline exposure at the workplace, especially if the acetylator polymorphism can be taken into account. 4-Aminodiphenyl hemoglobin adducts might be good parameters for monitoring individual smoking habits. The determination of urinary arylamine concentrations provides additional information concerning acute exposures to aromatic amines.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1246
    Keywords: Key words Chemical carcinogens ; List of MAK and BAT Values ; Cancer risk
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Carcinogenic chemicals in the work area are currently classified into three categories in section III of the German List of MAK and BAT Values (list of values on maximum workplace concentrations and biological tolerance for occupational exposures). 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, IIIB – be retained as Categories 1, 2, and 3, to correspond with European Union regulations. On the basis of our advancing knowledge of reaction mechanisms and the potency of carcinogens, these three categories are supplemented with two additional categories. The essential feature of substances classified in the new categories is that exposure to these chemicals does not contribute significantly to risk of cancer to man, provided that an appropriate exposure limit (MAK value) is observed. Chemicals known to act typically by nongenotoxic mechanisms and for which information is available that allows evaluation of the effects of low-dose exposures, are 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 are 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.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1335
    Keywords: Anticancer drugs ; Cytostatics ; Leukemia L1210 cells ; Nitrosourea ; Nitrososemicarbazide ; Mutagenicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Five experimental anti-leukemic agents, 1-(2-chloroethyl)-4-arylacyl-1-nitrososemicarbazides, were synthesized and tested for genotoxicity in theSalmonella/ mammalian microsome assay. No strong mutagenic activity could be detected when tested with theS. typhimurium TA98. A clear dose-dependent base-pair-substitution mutagenic activity was observed with each compound when the tester strain TA100 was used with or without metabolic activation. The genotoxicity of the unsubstituted substance was similar to that of the known mutagenic cytostatic drugs, lomustin and carmustin, and was stronger than the mutagenicity of each substituted derivative.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 0170-2041
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Aryl-Substituted Purines, I. - Synthesis of 7-Phenylguanine and of 2-Substituted 7-ArylhypoxanthinesThe synthesis of 7-phenylguanine (2) by cyclisation reaction of ethyl 4-amino-1-phenyl-5-imidazolecarboxylate (1a) with cyanamide is described. This reaction is the first and hitherto only synthetic approach to a hypothetical base adduct the significance of which is discussed in relation to the carcinogenesis of benzene. Moreover, the 2-substituted 7-arylhypoxanthines 4a-e have been prepared by reaction of ethyl 1-aryl-4-amino-5-imidazole-carboxylates 1a-c with thioamides 3a-c. Formic acid proved to be the best catalyst. By this new procedure starting compounds for the development of a radioimmuno assay for the trace analysis of 2 can be prepared in good yields.
    Notes: Die Synthese von 7-Phenylguanin (2) durch Cyclisierung von 4-Amino-1-phenyl-5-imidazolcarbonsäure-ethylester (1a) mit Cyanamid wird beschrieben. Die Reaktion gewährt den ersten und bisher einzigen Zugang zu einem hypothetischen Basenaddukt, dessen Bedeutung für die Benzolkanzerogenese zur Diskussion steht. Darüber hinaus wurden die 2-substituierten 7-Arylhypoxanthine 4a-e durch Reaktion von 1-Aryl-4-amino-5-imidazolcarbonsäure-ethylestern 1a-c und Thioamiden 3a-c dargestellt. Als bester Katalysator hat sich Ameisensäure erwiesen. Dieses neue Verfahren bietet einen guten Zugang zu Ausgangsverbindungen für die Entwicklung eines Radioimmunoassays zum Spurennachweis von 2.
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
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