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  • 1
    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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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 60 (1987), S. 150-153 
    ISSN: 1432-0738
    Keywords: Bleomycin ; Redox cycling ; Hydroxyl radical ; DNA damage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aerobic incubations of bleomycin, FeCl3, DNA, NADPH, and isolated liver microsomal NADPH-cytochrome P-450 reductase resulted in NADPH and oxygen consumption and malondialdehyde formation, indicating that the deoxyribose moiety of DNA was split. All parameters measured depended on the active enzyme, bleomycin and FeCl3. In the absence of oxygen malondialdehyde formation was very low. When bleomycin, FeCl3 and the reductase were incubated with methional ethene (ethylene) was formed, suggesting that during the enzyme-catalyzed redox cycle of bleomycin-Fe(III/II) hydroxyl radicals were formed. Ethene formation also depended on oxygen, NADPH, the enzyme, bleomycin, and FeCl3. During aerobic incubations of bleomycin, FeCl3, NADPH, and isolated liver nuclei oxygen and NADPH were consumed and malondialdehyde was formed. Oxygen and NADPH consumption and malondialdehyde formation depended on bleomycin and FeCl3. In the absence of oxygen malondialdehyde was not formed. These results indicate that nuclear NADPH-cytochrome P-450 reductase redox cycles the bleomycin-Fe(III/II) complex and that the reduced complex activates oxygen, whereby hydroxyl radicals are formed which damage the deoxyribose of nuclear DNA.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 103 (1982), S. 135-143 
    ISSN: 1432-1335
    Keywords: Bleomycin ; Lipid peroxidation ; Lung toxicity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Bleomycin was injected i.p. in rats, and the amount of expired ethane which indicateds lipid peroxidation was followed up for 78 h. Compared to controls neither 1x30 mg/kg and 2x30 mg/kg nor 1x70 mg/kg bleomycin led to increased ethane expiration, although body weight loss indicated toxicity. That pulmonary toxicity had been developed due to the acute bleomycin treatment could be demonstrated by histological examinations of lungs of the animals of the highest dosage group. The combined treatment of rats with bleomycin and ferrous ions neither resulted in an increase of ethane expired compared to that of the ferrous iontreated animals. Rather a decrease was observed. Our results indicate that acute bleomycin toxicity is not associated with increased lipid peroxidation. Furthermore, our data suggest that the bleomycin-ferrous-complex does not initiate lipid peroxidation in vivo.
    Type of Medium: Electronic Resource
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