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  • 11
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 66 (1975), S. 1396-1400 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 12
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Mutation Research Letters 91 (1981), S. 381-390 
    ISSN: 0165-7992
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 13
    ISSN: 1432-1335
    Keywords: Key words Chemical carcinogens ; List of MAK and BAT values ; Cancer risk ; carcinogen classification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Carcinogenic chemicals in the work area were previously classified into three categories in section III of the German List of MAK and BAT values (the list of values on maximum workplace concentrations and bio‐logical tolerance for occupational exposures). This classification was based on qualitative criteria and reflected essentially the weight of evidence available for judging the carcinogenic potential of the chemicals. In the new classification scheme the former sections IIIA1, IIIA2, and IIIB are 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 the risk of cancer to man, provided that an appropriate exposure limit (MAK value) is observed. Chemicals known to act typically by non-genotoxic 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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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Archives of dermatological research 281 (1989), S. 491-494 
    ISSN: 1432-069X
    Keywords: Epidermal keratinocytes ; Laser light ; Hematoporphyrin derivatives ; Lipid peroxidation ; Lysosomal enzymes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Human epidermal keratinocytes were grown in culture and the uptake of hematoporphyrin derivatives (HPDs) used in photodynamic therapy was estimated. Keratinocytes loaded with HPDs were irradiated with laser light of 632 nm generated by a helium-neon laser and cell toxicity was determined by the trypan blue exclusion test and the measurement of enzyme release. With increasing intracellular concentration of HPDs and with increasing intensity of the laser light, an increasing number of cells took up trypan blue and released the cytosolic enzyme lactate dehydrogenase and the lysosomal enzyme acid phosphatase after 1 h incubation of the irradiated cells at 37°C. Cytotoxicity was less pronounced when the irradiated cells were incubated at 0°C indicating the involvement of enzyme reactions in cell death. No lipid peroxidation as measured by malondialdehyde and ethane formation was detectable. Our results suggest that during photodynamic therapy with HPDs and laser light epidermal keratinocytes may be seriously damaged. The data indicate that not lipid peroxidation but rather the activation of lysosomal enzymes is responsible for the cytotoxicity observed.
    Type of Medium: Electronic Resource
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    International archives of occupational and environmental health 39 (1977), S. 27-32 
    ISSN: 1432-1246
    Keywords: Vinyl chloride ; Distribution in organs ; Inhibiton of vinyl chloride metabolism ; Vinylchlorid ; Gewebsverteilung ; Inhibition des Vinylchlorid-Stoffwechsels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Wird Vinylchlorid aus der Atmosphere eingeatmet, so stellt sich ein Gleichgewicht zwischen dem Vinylchlorid in der Luft und dem Organismus ein. In erster Linie reichert sich nicht metabolisiertes Vinylchlorid im Fettgewebe an. Für dieses Verteilungsverhalten dürfte die Lipophilie des Vinylchlorid Ausschlag gebend sein. Das Konzentrationsverhältnis von Vinylchlorid in einzelnen Organen bleibt über den gesamten untersuchten Konzentrationsbereich von 25 his 10.000 ppm Vinylchlorid in der Expositionsatmosphäre konstant. Aus dem Gleichgewicht wird Vinylchlorid dem Metabolismus zugeführt. Metabolite reichern sich, im Gegensatz zum unveränderten Vinylchlorid, vor allem in Leber und Niere an.
    Notes: Summary Rats have been pretieatet with 6-nitro-1.2.3-benzothiadiazole which completely blocks metabolism of vinyl chloride. If the animals are exposed to atmospheric vinyl chloride, formation of an equilibrium between the compound in the gas phase and in the animal's orgnism is observed. Unmetabolized vinyl chloride is concentrated in adipose tissue. The distribution pattern of vinyl chloride in different organs of the rat is constant over the concentration range of 25–10,000 ppm of vinyl chloride in the exposure atmosphere. Distribution of metabolites of vinyl chloride contrasts to that of the original compound; metabolites primarily are concentrated in liver and in kidneys.
    Type of Medium: Electronic Resource
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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 8 (1975), S. 301-307 
    ISSN: 1432-1041
    Keywords: Rifampicin ; enzyme induction ; oral contraceptives ; 17α-ethinyloestradiol ; oestradiol ; cytochrome P-450
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Liver biopsies were obtained from four patients treated with rifampicin 600 mg for 6–10 days. Hepatic microsomes were incubated with an NADPH-regenerating system and the substrates [2, 4, 6, 7--3H] oestradiol, [6, 7-3H] oestradiol, [2, 4, 6, 7-3H] ethinyloestradiol and [6, 7-3H] ethinyloestradiol. The hydroxylation rates of these steroids at the labelled positions of rings A and B were determined by measuring the transformation of tritium into HTO by the microsomal enzymes. Comparison with previously published data showed that treatment with rifampicin caused a fourfold increase in the rate of hydroxylation of oestradiol and ethinyloestradiol at positions C-2/C-4 of ring A and C-6/C-7 of ring B. The acceleration of oestrogen hydroxylation by rifampicin was paralleled by an increase in microsomal cytochrome P-450, and also by microsomal reduction of rifampicin-quinone, a reactive metabolite of rifampicin. The increased aromatic hydroxylation of oestradiol and ethinyloestradiol leads to enhancement of their irreversible binding to microsomal protein. The data provide an explanation for the diminished efficacy of oestrogens in contraceptive formulations given to patients under treatment with rifampicin.
    Type of Medium: Electronic Resource
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 49 (1982), S. 265-273 
    ISSN: 1432-0738
    Keywords: Isolated hepatocytes ; Carbon tetrachloride ; Ferrous ions ; Lipid peroxidation ; Ethane ; n-Pentane
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Isolated rat hepatocytes (1×107 cells/ml) were aerobically incubated in Eagle's Minimum Essential Medium which contained 2.0% albumin. As potential parameters of lipid peroxidation ethane and n-pentane formed were measured in samples obtained from the gas phase above the incubation mixture. 15–30 nmol ethane or n-pentane were produced by 107 hepatocytes within 90 min. Carbon tetrachloride (CCl4) or ADP-complexed ferrous ions stimulated ethane and n-pentane formation considerably, depending on the concentrations of the compounds. With CCl4 107 cells formed max 180 nmol ethane and 140 nmol n-pentane within 90 min incubation, whereas with Fe(II) max 130 nmol ethane and 220 nmol n-pentane could be detected. When n-pentane was added to the gas phase above the incubation mixture containing either medium or medium plus hepatocytes its amount decreased by 30% within the first 5 min of incubation. However, afterwards only minor amounts of n-pentane disappeared, even in the presence of hepatocytes. This indicates that n-pentane equilibrates with the cell suspension under the conditions used. Cell viability, as determined by the release of lactate dehydrogenase into the medium and by the uptake of trypan blue by the cells, and the recovery of the cells decreased only in presence of relatively high concentrations of CCl4, or Fe(II) respectively. However, a maximal effect on ethane and n-pentane formation was reached already with lower concentration.
    Type of Medium: Electronic Resource
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 52 (1983), S. 135-147 
    ISSN: 1432-0738
    Keywords: Lipid peroxidation ; Ethane ; Pentane
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The use of exhalation of ethane and n-pentane in experimental animals as parameters of lipid peroxidation led to an examination of pharmacokinetics of both compounds in rats. When rats were exposed, in a closed desiccator jar chamber, to a wide range of ethane concentrations, linear elimination pharmacokinetics were observed. n-Pentane, when concentrations higher than 100 ppm were applied, displayed saturation kinetics. These were formally explained by action of two competing metabolizing pathways or enzymes. Application of preexisting models could describe exhalation of both ethane and n-pentane by untreated control rats. Stimulation of lipid peroxidation by ferrous ions or by carbon tetrachloride resulted in dissimilar quantitative behaviours of ethane and n-pentane. Ethane production rates were enhanced after application of both compounds. Because of relatively slow metabolic eliminations this led to markedly elevated concentrations of ethane in the gas phase of the system. Pentane production rates were simultaneously enhanced. However, difficulties in interpretation arise because of rapid metabolic elimination of n-pentane. Compounds that diminish pentane metabolism are shown to evoke higher pentane concentrations in the system than compounds which only enhance the pentane production rate. Determinations of ethane exhalation should provide a more favourable parameter of lipid peroxidation than exhalation of pentane.
    Type of Medium: Electronic Resource
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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 39 (1977), S. 31-39 
    ISSN: 1432-0738
    Keywords: Catechols ; Isoproterenol ; Ethinyloestradiol ; Covalent protein binding ; Reactive metabolites ; Rat liver microsomes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Wenn Ratten mit 14 μg/kg 3H-Isoproterenol behandelt wurden, konnte bis 48 h danach in der Leber 3H-Radioaktivität gemessen werden. Diese Menge war nicht unterschiedlich in Lebern von Tieren, welche mit Diäthylmaleat vorbehandelt waren. Nach erschöpfender Extraktion konnte eine beträchtliche Menge an 3H-Radioaktivität aus Isoproterenol in den Proteinen von Gesamtleber (Homogenat), Cytosol und von Mikrosomen gefunden werden. In der Cytosolfraktion von Diäthylmaleat vorbehandelten Tieren wurde die zweifache Menge von Isoproterenol-Radioaktivität in den extrahierten Proteinen gefunden, im Vergleich zu Kontrollen. In der mikrosomalen Fraktion gab es keinen Unterschied bei der Radioaktivitätsmenge, die in Proteine eingebaut war. In allen Fraktionen nahm die Radioaktivität, die in den extrahierten Proteinen meßbar war, mit einer Halbwertszeit von etwa 24 h ab. Die in vivo-Ergebnisse über kovalente Proteinbindung von Isoproterenol werden verglichen mit der irreversiblen Proteinbindung von Äthinylöstradiol in vivo. Quantitativ werden diese in vivo-Befunde mit den Resultaten zur irreversiblen Proteinbindung verglichen, die während Inkubationen von Isoproterenol oder Äthinylöstradiol mit Rattenlebermikrosomen erhalten wurden.
    Notes: Abstract When rats were dosed with 14 μg/kg 3H-isoproterenol, 3H-radioactivity was measurable in the liver until 48 h. This amount was not different in livers of animals which have been pretreated with diethyl maleate. After exhaustive extraction, a significant amount of 3H-radioactivity from isoproterenol could be detected in the proteins of total liver (homogenate), of cytosol and of microsomes. In the cytosol fraction of diethyl maleate pretreated animals twice the amount of isoproterenol-radioactivity was found in the extracted proteins compared to controls. In the microsomal fraction there was no difference between diethyl maleate pretreated and control animals in the amount of radioactivity incorporated into proteins. In all fractions the radioactivity measurable in the extracted proteins declined with a half life time of about 24 h. The in vivo results on covalent binding of isoproterenol are compared to the irreversible protein binding of ethinyloestradiol in vivo. Quantitatively, these in vivo data are compared to the results on irreversible protein binding obtained during incubations of isoproterenol or ethinyloestradiol with rat liver microsomes.
    Type of Medium: Electronic Resource
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  • 20
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 60 (1987), S. 144-149 
    ISSN: 1432-0738
    Keywords: Redox cycling ; Oxygen radicals ; Lipid peroxidation ; DNA damage ; Protein alteration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The toxic effects of compounds which undergo redox cycling via enzymatic one-electron reduction are reviewed. First of all, the enzymatic reduction of these compounds leads to reactive intermediates, mainly radicals which react with oxygen, whereby superoxide anion radicals are formed. Further oxygen metabolites are hydrogen peroxide, singlet oxygen and hydroxyl radicals. The role of these oxygen metabolites in toxicity is discussed. The occurrence of lipid peroxidation during redox cycling of quinonoide compounds, e.g., adriamycin, and the possible relationship to their toxicity is critically evaluated. It is shown that iron ions play a crucial role in lipid peroxidation induced by redox cycling compounds. DNA damage by metal chelates, e.g., bleomycin, is discussed on the basis of findings that enzymatic redox cycling of a bleomycin-iron complex has been observed. The involvement of hydroxyl radicals in bleomycin-induced DNA damage occurring during redox cycling in cell nuclei is claimed. Redox cycling of other substances, e.g., aromatic amines, is discussed in relation to carcinogenesis. Other chemical groups, e.g., nitroaromatic compounds, hydroxylamines and azo compounds are included. Other targets for oxygen radical attack, e.g., proteins, are also dealt with. It is concluded that oxygen radical formation by redox cycling may be a critical event in toxic effects of several compounds if the protective mechanisms of cells are overwhelmed.
    Type of Medium: Electronic Resource
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