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Effect of low level laser therapy on oxidative stress and DNA-damage response in oral mucosa cells exposed to chemotherapy agents and gamma radiation: in vitro study

Grant number: 18/19028-6
Support type:Regular Research Grants
Duration: February 01, 2019 - January 31, 2021
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Luciana Corrêa
Grantee:Luciana Corrêa
Home Institution: Faculdade de Odontologia (FO). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Maria Cristina Zindel Deboni ; Maria Fátima Guarizo Klingbeil ; Monica Beatriz Mathor

Abstract

Low level laser therapy has been adopted for the prevention and treatment of oral mucositis. This lesion is derived from an intense oxidative stress caused by radiotherapy and chemotherapy. The oxidative stress induces the formation of oxidized bases and activates a DNA-damage response (DDR) in neoplastic and normal cells. The DDR is composed mainly by mechanisms of non-homologous end-joining, homologous recombination, and base excision. The effect of low level laser therapy on oxidative stress and DDR in oral keratinocytes exposed to chemotherapy and radiotherapy was not addressed yet. In this study we aim to verify whether the laser therapy with different energy parameters (0,2J - 6,6J/cm2; 0,4J - 13,3J/cm2; 1J - 33,3J/cm2, 2J - 66,6J/cm2) reduces the oxygen reactive species and oxidized bases, as well as alters the expression of antioxidative proteins in normal oral keratinocytes treated with gamma radiation or chemotherapy agents (5- fluorouracil, melphalan, and methotrexate). We aim also to investigate whether the laser therapy reduces the DNA fragmentation and modifies the expression of DDR-related proteins (g-H2AX, ERCC1, OGG1, ATM e p53). Our intention is to demonstrate whether laser therapy can reduce the genotoxic effect of antineoplastic agents in normal oral keratinocytes and what energy range is more appropriate. (AU)