Photosensitized Reactions of Oxidative Damage to Biomolecules: Role in Genotoxic and Cytotoxic Processes

Photosensitized oxidation reactions of biomolecules, such as lipids, proteins, and DNA, initiate cytotoxic and genotoxic processes that are mediated by endogenous sensitizers under effect of ultraviolet radiation in the range A (UVA, 320–400 nm) on living systems. The photosensitization reactions are oxygen-dependent and are divided into type I and type II based on their primary mechanism. Type I reactions involve electron transfer between photoexcited sensitizer and biomolecule with the formation of radical states. The interaction of a radical cation of biomolecule with oxygen leads to the production of its final oxidation products, and electron transfer between a radical anion of sensitizer and oxygen generates superoxide anion radical ( \({\text{O}}_{2}^{{ \bullet - }}\) ) with the following production of H₂O₂ and the highly reactive hydroxyl radical (^•OH). In contrast to radical mechanism of type I reactions, primary mechanism of type II reactions involves energy transfer from a photoexcited sensitizer to oxygen (O₂) that leads to the formation of singlet oxygen (¹O₂, ¹Δg), which is much more reactive in relation to biomolecule oxidation than O₂. Current knowledge on mechanisms of initial stages of the type I and type II reactions, as well as their involvement in the oxidized degradation of biomolecules, such as DNA, proteins, and lipids, are expounded in detail in present review. Sensitized properties of pterins, riboflavin, and protoporphyrin IX with characteristic peculiarities of action of each of these photosensitizers are also considered. Considerable attention is given to processes of photosensitized damage to DNA and discussing the role of different DNA photoproducts in initiating genotoxic processes, including carcinogenesis in human skin.