EFFECTS OF GAMMA-IRRADIATION ON CELLS AND THEIR CONSTITUENTS

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The effects of ionizing and ultraviolet radiation, of visible light, and of ultrasound on cells and their constituents are being studied. Certain tetrasulfonated phthalocyanines with maximum absorption in the 600-700 nm region and cyanine dyes (700-800 nm) are efficient photosensitizers for killing mammalian cells and appear to be promising candidates to replace hematoporphyrin derivative (Hpd) in photodynamic therapy (PDT) of tumors. The photochemical quantum yields for singlet oxygen formation from several tetrasulfonated phthalocyanines were measured. Those containing paramagnetic metals (copper, iron, vanadyl) do not generate singlet oxygen in contrast to those with diamagnetic metals (aluminum, zinc). The latter are efficient photosensitizers, while the former have no photobiological activity in the killing of mammalian cells. Similar results were found for the Type I photochemical ability as measured by one electron transfer to methyl viologen (paraquat) dication. The menadione sensitized photooxidation of nucleic acids and protein constituents was studied by ESR and spin trapping. The observed radical intermediates and stable products can be explained in terms of electron transfer from the substrate to the triplet state of menadione to form the radical cation of the substrate and the anion radical of menadione. A new method of introducing singlet oxygen as the only damaging species into aqueous solutions or into monolayers of mammalian cells was developed. This approach avoids complications due to Type I processes (hydrogen and/or electron-transfer) between the triplet state of the photosensitizer and the substrate and makes it possible to study the photobiological effects of Type II processes (singlet oxygen) alone.