DNA strand scission and base release photosensitized by metallo-phthalocyanines

Photoirradiation of aqueous solutions of DNA in the presence of Al- or Zn-tetrasulphonated phthalocyanines (AIPcS4 and ZnPcS4) causes formation of strand breaks and liberation of nucleobases. The effect of added D2O, which enhances singlet oxygen (1O2) lifetime, radical scavengers including alcohols and the spin-trap DMPO, as well as superoxide dismutase, indicates that both singlet oxygen (1O2) and free radicals contribute to the production of strand breaks. However, in the case of base release, only free radicals, such as the hydroxyl radical (.OH), appear to be involved in the degradation process. Detection of the characteristic free-radical oxidation products of deoxyribose provides evidence that .OH are involved in the photosensitized DNA damage. EPR and spin trapping data suggest that superoxide (O2.-) is the most likely precursor of .OH and a Fenton-type mechanism is proposed for their formation.