Free radical damage to deoxyribose by anthracycline, aureolic acid and aminoquinone antitumour antibiotics. An essential requirement for iron, semiquinones and hydrogen peroxide.
Anthracycline, aureolic acid and aminoquinone antitumour antibiotics damage deoxyribose in cell-free systems when reduced in air by the enzyme ferredoxin reductase. Damage to deoxyribose is inhibited by the iron chelator desferrioxamine, the copper-containing protein caeruloplasmin and catalase but not by superoxide dismutase. Scavengers of the hydroxyl radical such as formate, butan-1-ol, ethanol and benzoate do not offer much protection, whereas mannitol and thiourea do. These findings point to a site-specific Fenton reaction in which the drug semiquinones reduce complexed iron and dioxygen leading to the formation of hydrogen peroxide and a ferrous complex.
D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D016227:Benzoquinones; D002374:Catalase / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D003855:Deoxyribose; D006861:Hydrogen Peroxide; D006878:Hydroxides; D017665:Hydroxyl Radical; D007501:Iron; D009279:Naphthacenes / Q000633:toxicity; D008926:Plicamycin / Q000633:toxicity*; D011809:Quinones; D013482:Superoxide Dismutase / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D016227:Benzoquinones; D006878:Hydroxides; D009279:Naphthacenes; D011809:Quinones; C025232:semiquinone radicals; D017665:Hydroxyl Radical; D003855:Deoxyribose; D006861:Hydrogen Peroxide; D007501:Iron; D002374:Catalase; D013482:Superoxide Dismutase; D003676:Deferoxamine; D008926:Plicamycin