PHOTOSENSITIZED FORMATION OF 8-HYDROXY-2'-DEOXYGUANOSINE AND DNA STRAND BREAKAGE BY A CATIONIC MESOSUBSTITUTED PORPHYRIN

Cationic porphyrins, known to have a high affinity for DNA, are useful tools with which to probe a variety of interactions with DNA. In this study we have examined both DNA strand scission and oxidative DNA bas e damage, measured by 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation, using a photoactivated cis-dicationic porphyrin. The data demonstrated a dose-dependent formation for each type of DNA damage. Inhibition of strand scission and 8-OHdG formation with the singlet oxygen scavenge r 1,3-diphenylisobenzofuran and with MgCl2 and no apparent effect by D 2O suggests that a singlet oxygen mechanism generated in close proximi ty to the DNA may be responsible for the damage. However, a nearly com plete inhibition of 8-hydroxy-2'-deoxyguanosine formation in 75% D2O a nd the substantial enhancement of 8-hgdroxy-2'-deoxyguanosine formatio n in a helium atmosphere by photoactivated porphyrin rules out singlet oxygen as a primary mechanism for this process. These data indicate t hat distinct mechanisms lead to 8-OHdG formation and strand scission a ctivity.