Structural specificity of polyamines and polyamine analogues in the protection of DNA from strand breaks induced by reactive oxygen species.
Reactive oxygen species are known to induce strand breaks and/or base modifications in DNA. DNA strand breaks are associated with many pathologies and programmed cell death. We have examined the ability of the polyamines and their analogues to protect phi X-174 plasmid DNA from strand breakage induced by a oxygen-radical generating system. Spermine and several unsymmetrically substituted polyamine analogues reduced the amount of strand breakage at a physiologically relevant concentration of 1 mM. However, putrescine, spermidine, N1-acetylspermine, N1-acetylspermidine and symmetrically alkylated polyamine analogues were not able to reduce strand breakage at the same concentration. Thus, the unsymmetrically alkylated polyamine analogues and natural spermine can protect DNA against strand breakage induced by Cu(II)/H2O2 generated ROS similar to other more classical antioxidants.
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Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland 21205, USA.
Yager
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Woster
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Casero
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D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D010584:Bacteriophage phi X 174 / Q000187:drug effects / Q000235:genetics; D015317:Biogenic Polyamines / Q000737:chemistry* / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D011073:Polyamines / Q000494:pharmacology; D011700:Putrescine / Q000494:pharmacology; D017382:Reactive Oxygen Species; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D000975:Antioxidants; D015317:Biogenic Polyamines; D011073:Polyamines; D017382:Reactive Oxygen Species; C059685:N(1),N(11)-diethylnorspermine; C083629:N(1)-ethyl-N-(11)-((cyclopropyl)methyl)-4,8-diazaundecane-1,11-diamine; D013096:Spermine; D003300:Copper; D006861:Hydrogen Peroxide; C029892:cupric chloride; D013095:Spermidine; D011700:Putrescine