PHOTOSENSITIZED FORMATION OF 8‐HYDROXY‐2′‐DEOXYGUANOSINE AND DNA STRAND BREAKAGE BY A CATIONIC meso‐SUBSTITUTED PORPHYRIN

Abstract 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 base damage, measured by 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) formation, using a photoactivated cis‐dicationic por‐phyrin. 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 scavenger 1,3‐diphenylisobenzofuran and with MgCl2 and no apparent effect by D2O suggests that a singlet oxygen mechanism generated in close proximity to the DNA may be responsible for the damage. However, a nearly complete inhibition of 8‐hydroxy‐2′‐deoxyguanosine formation in 75% D2O and the substantial enhancement of 8‐hydroxy‐2′‐deoxyguanosine formation in a helium atmosphere by photoactivated porphyrin rules out singlet oxygen as a primary mechanism for this process. These data indicate that distinct mechanisms lead to 8‐OHdG formation and strand scission activity.