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Analyses of the protective effect of acetohexamide in UV-irradiated Xeroderma pigmentosum cells

Grant number: 19/13919-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): January 01, 2020
Effective date (End): December 31, 2020
Field of knowledge:Biological Sciences - Genetics - Mutagenesis
Principal Investigator:Carlos Frederico Martins Menck
Grantee:Danilo Batista Vieira de Melo
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

DNA is a molecule that undergoes constant attacks of genotoxic agents, either of endogenous or exogenous origins. These interactions can generate lesions in DNA and subsequently mutations. To prevent such damage, our cells have several DNA repair mechanisms, which preserve the genome. People who have disabilities in these mechanisms have clinical pictures related to high frequency of tumors, early aging, and neurodegeneration. Given the importance of these mechanisms, the project focuses on studies using human cells derived from patients with disabilities in nucleotide excision repair (NER) and carriers of the syndrome xeroderma pigmentosum (XP), who present increased frequency of skin lesions, including cancer, in the sun-exposed areas. The proposal is to use cell culture techniques to analyze cellular responses, including cell viability, to ultraviolet (UV) irradiation, after pre-treatment with acetohexamide. This drug was recently reported in the literature with a protective effect on UVC irradiation in XPA-deficient strains. In this study, we intend to confirm this protective effect in XP cells and test its effect also in cells deficient for the XPC protein. If we can confirm the protective effect of this substance in cell viability, we will implement efforts to understand the mechanisms involved in the process by evaluating different responses of cells to DNA damage. Our expectation is that the evidence may indicate this substance as a potential therapeutic agent for patients with this syndrome.