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  • 1
    ISSN: 1432-1335
    Schlagwort(e): Nitroalkylamines ; Hepatocytes ; Metabolizing enzymes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary N-nitrodimethylamine is metabolized oxidatively to N-nitrohydroxymethylmethylamine, which decomposes to yield formaldehyde and N-nitromethylamine. All four compounds and N-nitroethylamine were tested for their ability to induce DNA single strand breaks in hepatocytes and in SV 40-transformed Chinese hamster embryo cell lines. Only the two monoalkylnitramines were positive. They induced single strand breaks in hepatocytes, but were not effective in the other cells. Formaldehyde and N-nitrohydroxymethylmethylamine were toxic to the cells. None of the compounds tested was able to induce selective DNA amplification in the two transformed cell lines. Enzymes involved in drug metabolism were assayed in the hamster cell lines. The activity of UDP-glucuronosyltransferase and cytosolic epoxide hydrolase were not detectable. N-nitrodimethylamine demethylation was low. The content of reduced glutathione and the activities of glutathione transferase and membrane bound epoxide hydrolase were comparable to values obtained in the rat liver.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1432-1335
    Schlagwort(e): Disulfiram ; Nitrosodialkylamine ; Carcinogenesis ; Drug-metabolizing enzymes ; Glutathione
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The influence of a prolonged treatment with disulfiram (DSF) andd(-)penicillamine (PA) on biological and biochemical effects induced by nitrosodiethylamine (NDEA) was studied in rats. The combination of NDEA and DSF led to a massive and early development of esophageal tumors, which were fatal to the animals. No liver tumors were observed in this group, whereas PA in combination with NDEA led to an increased development of liver tumors compared with NDEA alone. In the last two groups, only incidental tumors of the esophagus were observed. Nasal cavity tumors also appeared earlier in the animals treated with DSF and NDEA than in animals treated with NDEA alone or with NDEA plus PA. At a biochemical level, DSF led to a significant inhibition of hepatic anilinehydroxylase and nitroso-dimethylaminedemethylase in contrast to PA, which had no influence on these enzymes. The reduced activities of these drug-metabolizing enzymes did not appear to be related to gross cytochrome P450 content. Highly significant increases in glutathione content and glutathione-S-transferase activity (GSH/GST) were induced by DSF but not by PA. Because N-nitrosodiethylamine requires enzymatic activation to form the ultimate carcinogen, it is suggested that the observed inhibition of nitrosamine-transforming enzymes in the liver during DSF treatment leads to an increased amount of intact nitrosamines in other organs, e.g., in the esophagus, where it could be transformed to the ultimate carcinogen. DSF treatment alone or in combination with NDEA leads to an accumulation of trace elements in the liver, whereas PA eliminated copper and cobalt. The possible influence of these elements on tumor development is discussed in part II of this study.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1432-1335
    Schlagwort(e): Nitrosodiethylamine ; Liver tumors ; Disulfiram ; d-penicillamine ; Trace elements ; Rats
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The influence of a 28-week treatment with disulfiram (DSF),d-penicillamine (PA), and nitrosodiethylamine (NDEA), as well as with a combination of DSF or PA with NDEA on the concentrations of eight essential trace elements in the whole liver tissue of rats was measured by means of neutron activation analysis. While NDEA treatment lowered the Zn content of the liver, DSF alone or in combination with NDEA enhanced the Zn and Se concentration by 50%–80%. Co, Cu, and Cd levels were increased by factors of 10, 60, and 110, respectively. The Mo concentration was decreased by 50% after DSF administration. PA reduced Cu, Co, and Zn in the liver. PA/NDEA treatment also lowered Cu, Co, and Zn content, but there was no strengthening effect of PA on the decrease in Zn observed with NDEA. The change of trace element concentrations, especially of Cu, is discussed with regard to the observed tumor induction in the liver, which tended to be increased by a combined NDEA/PA administration compared with NDEA treatment alone, whereas a protective action of DSF against NDEA induced liver tumors could not be established.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Journal of cancer research and clinical oncology 110 (1985), S. 244-246 
    ISSN: 1432-1335
    Schlagwort(e): High fat diet ; Vitamin A ; Vitamin E ; Reduced glutathione
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Mammary tumor development induced by methylnitrosourea in female Sprague-Dawley rats had no significant effect on hepatic glutathione levels. If the diets of methylnitrosourea-treated animals were supplemented with vitamin A and E an increased hepatic glutathione level was observed initially. A high fat diet (21% per weight) supplemented with the two vitamins led to a decreased hepatic glutathione level 2 months after tumor induction. Advanced tumor development under any of the diets tested had no effect on hepatic glutathione.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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