Adriamycin: the role of lipid peroxidation in cardiac toxicity and tumor response.
The antitumor antibiotic, adriamycin, induces severe cardiac toxicity associated with peroxidation of cardiac lipids in mice. Both this lipid peroxidation and cardiac toxicity of adriamycin are reduced by prior treatment of the animals with the free radical scavenger tocopherol. Such treatment with tocopherol does not, however, alter the magnitude or duration of the adriamycin-induced suppression of DNA synthesis in P388 ascites tumor, nor does it diminish the antitumor responsiveness of P388 ascites tumor. These results suggest that adriamycin has at least two mechanisms of tissue damage: one, which involves lipid peroxidation, is blocked by tocopherol and results in cardiac toxicity; the other, which involves binding to DNA, is not antagonized by tocopherol and is responsible for tumor response.
D000818:Animals; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000627:therapeutic use / Q000633:toxicity*; D004359:Drug Therapy, Combination; D006321:Heart / Q000187:drug effects*; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D010545:Peroxides / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology* / Q000627:therapeutic use
D004273:DNA, Neoplasm; D010545:Peroxides; D014810:Vitamin E; D004317:Doxorubicin