Abstract
The antitumor properties of the anthracyclines, including adriamycin, which shows the broadest activity clinically, correlate with their capacity to bind intercalatively to duplex DNA, although other cellular effects appear to be significant. The administration of adriamycin and daunorubicin is accompanied by severe risk of cardiotoxicity. Growing evidence indicates that this side effect may be related to factors, including the accumulation of the drug in cardiac tissue; reductive enzymatic activation at the chromophore, which in the presence of oxygen produces reactive oxygen species; concomitant oxidative damage of membrane lipids; and the diminished levels in the heart of enzymes, which effect protection against cellular oxidative lesions. Assays designed to detect and quantify the production of individual reactive oxygen species from activated anthracyclines may, therefore, be useful in comparing drugs designed to alleviate this serious clinical limitation of cardiotoxicity.
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