Strand scission of DNA by bound adriamycin and daunorubicin in the presence of reducing agents. |
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Authors: | J W Lown S K Sim K C Majumdar R Y Chang |
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Affiliation: | Department of Chemistry, The University of Alberta Edmonton, Alberta, Canada T6G 2G2 |
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Abstract: | Adriamycin and daunorubicin bound to covalently closed circular DNA nick the latter when reduced by sodium borohydride as demonstrated using an ethidium bromide fluorescence assay. The degradation, dependent on oxygen, is strongly inhibited by (i) superoxide dismutase (ii) catalase and (iii) sodium benzoate indicating the intermediacy in the cleavage of superoxide radical anion, hydrogen peroxide and hydroxyl radicals respectively. Less nicking of the DNA is observed by the reduced aglycones, so binding to the DNA by the aminosugar moiety assists the cleavage process. Adriamycin, daunorubicin and both ring C reduced forms bind intercalatively and completely relax supercoiled DNA. The results provide a possible rationale for the degradation of DNA which accompanies anthracycline administration. |
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