STRUCTURAL SPECIFICITY OF POLYAMINES AND POLYAMINE ANALOGS 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 patho logies and programmed cell death. We have examined the ability of the polyamines and their analogues to protect phi X-174 plasmid DNA from s trand breakage induced by a oxygen-radical generating system. Spermine and several unsymmetrically substituted polyamine analogues reduced t he amount of strand breakage at a physiologically relevant concentrati on of 1 mM. However, putrescine, spermidine, N-1-acetylspermine, N-1-a cetylspermidine and symmetrically alkylated polyamine analogues were n ot able to reduce strand breakage at the same concentration. Thus, the unsymmetrically alkylated polyamine analogues and natural spermine ca n protect DNA against strand breakage induced by Cu(II)/H2O2 generated ROS similar to other more classical antioxidants. (C) 1998 Academic P ress.