DNA strand scission induced by adriamycin and aclacinomycin A.
The binding of adriamycin and aclacinomycin A with PM2 DNA, and the consequent cleavage of DNA have been demonstrated by agarose gel electrophoresis, using an ethidium bromide assay. Adriamycin was observed to induce a single strand scission of DNA in the presence of a reducing agent, but aclacinomycin A caused much less degree of DNA breaks. The DNA cleavage was enhanced by Cu2+ and Fe2+, but not significantly by Ni2+, Zn2+, Mg2+ and Ca2+, suggesting that reduction and auto-oxidation of the quinone moiety and H2O2 production participate in the DNA-cutting effect. The DNA degradation was dependent upon concentrations of the anthracyclines and CuCl2. The degree of DNA cleavage at 0.04 mM adriamycin was similar to that at 0.4 mM aclacinomycin A in the presence of 1 mM NADPH and 0.4 mM CuCl2. DNA was degraded to small fragments at 0.4 mM adriamycin and 0.2 mM CuCl2. The anthracycline-induced DNA cleavage was stimulated by H2O2, but partially inhibited by potassium iodide, superoxide dismutase, catalase and nitrogen gas atmosphere. The results suggested that both free radical of anthracycline quinones and hydroxyl radical directly react with DNA strands.
D000903:Antibiotics, Antineoplastic; D002374:Catalase; D055598:Chemical Phenomena; D002621:Chemistry; D003300:Copper; D004247:DNA; D004317:Doxorubicin; D006861:Hydrogen Peroxide; D008670:Metals / Q000494:pharmacology; D009279:Naphthacenes; D009584:Nitrogen; D011193:Potassium Iodide; D013482:Superoxide Dismutase
D000903:Antibiotics, Antineoplastic; D008670:Metals; D009279:Naphthacenes; D011193:Potassium Iodide; D003300:Copper; D004317:Doxorubicin; D004247:DNA; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D009584:Nitrogen