Direct participation of DNA in the formation of singlet oxygen and base damage under UVA irradiation

• Published in: Free radical biology & medicine Vol. 108; pp. 86 - 93
• Main Authors: Yagura, Teiti, Schuch, André Passaglia, Garcia, Camila Carrião Machado, Rocha, Clarissa Ribeiro Reily, Moreno, Natália Cestari, Angeli, José Pedro Friedmann, Mendes, Davi, Severino, Divinomar, Bianchini Sanchez, Angelica, Di Mascio, Paolo, de Medeiros, Marisa Helena Gennari, Menck, Carlos Frederico Martins
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-07-2017
• Subjects: Animals; Antibodies, Antinuclear - metabolism; Cattle; Cell-Free System; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - chemistry; Deoxyguanosine - metabolism; DNA - chemistry; DNA - immunology; DNA - radiation effects; DNA Damage; Oxidative Stress; Photosensitivity Disorders; Pyrimidine Dimers - chemistry; Singlet oxygen; Singlet Oxygen - chemistry; Sodium Chloride - metabolism; Sunlight; Thymus Gland - physiology; Ultraviolet radiation; Ultraviolet Rays - adverse effects; Ultraviolet radiation; DNA damage; Singlet oxygen
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2017.03.018

UVA light is hardly absorbed by the DNA molecule, but recent works point to a direct mechanism of DNA lesion by these wavelengths. UVA light also excite endogenous chromophores, which causes DNA damage through ROS. In this study, DNA samples were irradiated with UVA light in different conditions to investigate possible mechanisms involved in the induction of DNA damage. The different types of DNA lesions formed after irradiation were determined through the use of endonucleases, which recognize and cleave sites containing oxidized bases and cyclobutane pyrimidine dimers (CPDs), as well as through antibody recognition. The formation of 8-oxo-7,8-dihydro-2′-deoxyguanine (8-oxodG) was also studied in more detail using electrochemical detection. The results show that high NaCl concentration and concentrated DNA are capable of reducing the induction of CPDs. Moreover, concerning damage caused by oxidative stress, the presence of sodium azide and metal chelators reduce their induction, while deuterated water increases the amounts of oxidized bases, confirming the involvement of singlet oxygen in the generation of these lesions. Curiously, however, high concentrations of DNA also enhanced the formation of oxidized bases, in a reaction that paralleled the increase in the formation of singlet oxygen in the solution. This was interpreted as being due to an intrinsic photosensitization mechanism, depending directly on the DNA molecule to absorb UVA and generate singlet oxygen. Therefore, the DNA molecule itself may act as a chromophore for UVA light, locally producing a damaging agent, which may lead to even greater concerns about the deleterious impact of sunlight.
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•Production of 1O2 by UVA light in a cell-free system depends on the presence of DNA.•8-oxodG is induced due to the formation of 1O2 by DNA absorption of UVA photons.•DNA molecule itself acts as a UVA-photosensitizer.