Genotoxic effects after exposure of cells with deficiencies in DNA repair to blue light

• Grant number: 20/12560-4
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): September 01, 2021
• Effective date (End): August 31, 2023
• Field of knowledge: Biological Sciences - Biophysics - Radiology and Photobiology
• Principal researcher: Carlos Frederico Martins Menck
• Grantee: Paulo Newton Tonolli
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 19/19435-3 - The role of DNA damage and mitochondrial function in vascular, immune and neurological ageing (DNA MoVINg), AP.TEM

Abstract

People with xeroderma pigmentosum (XP), a rare autosomal genetic disease, have defects in the repair of DNA nucleotide lesions induced by ultraviolet radiation (UV), the nucleotide excision repair (NER) pathway. XP patients are highly sensitive to solar radiation, showing skin lesions on minimal exposure to the sun, and high incidence of skin cancer compared to the general population. Studies have reported the importance of photoinduced stress by UVA radiation in decreasing the efficiency of DNA repair mechanisms and the consequent increase in mutagenesis and carcinogenesis in XP patients. However, the influence of visible light, a region of the solar spectrum with a relevant role in the photosensitization reactions and photoinduced stress, in XP cells is not known yet. In this project, we aim elucidating the effects of the exposure of cells XP-C (deficient NER) and XP-V (competent NER, but with defective DNA translesion synthesis) to blue light, the most damaging portion of visible light, and whether it is able to decrease the efficiency of repair mechanisms, increasing DNA damage, mutagenesis and carcinogenesis. In addition, the accumulation of the pigment lipofuscin, a by-product of oxidative damage in cells such as those induced by exposure to UVA radiation, and its sensitization by blue light in XP-V and XP-C cells and DNA damage will be investigated. Thus, this project intends to answer if blue light is dangerous to XP cells, raising the necessity for new photoprotection policies, especially for XP patients who are highly susceptible to the damage caused by solar radiation. (AU)