The effects of the quinone type drugs on hydroxyl radical (OH.) production by rat liver microsomes.
The quinone drugs are known to be metabolized to semiquinone free-radical intermediates and to enhance NADPH oxidation in microsomal system. The effect of adriamycin and mitomycin C on the decarboxylation of [14C] carboxyl benzoate via hydroxyl radical (OH.) production in the microsomal system was examined. The activity of these drugs was compared to 5-fluorouracil, cyclophosphamide, and methotrexate, which are inactive in oxygen consumption experiments and are non-quinone-type drugs. Adriamycin and mitomycin C stimulated decarboxylation of benzoate 100 and 50% above the controls, respectively, while 5-fluorouracil, cyclophosphamide, and methotrexate were not different from controls. Addition of superoxide dismutase increased benzoate decarboxylation with or without the drugs present, while catalase was inhibitory in both circumstances. These results suggest that the quinone drugs enhanced hydroxyl radical (OH.) production by liver microsomes, and offer a possible mechanism of cellular toxicity by these agents.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000032:analysis; D002250:Carbon Radioisotopes; D002262:Carboxy-Lyases / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010101:Oxygen Consumption; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000494:pharmacology
D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; D011809:Quinones; D002245:Carbon Dioxide; D008353:Mannitol; D013482:Superoxide Dismutase; D002262:Carboxy-Lyases; D004121:Dimethyl Sulfoxide