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Effect of low level laser therapy on DNA damage and repair in oral keratinocytes exposed to different chemotherapeutic agents

Grant number: 18/19738-3
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): March 01, 2019
Effective date (End): February 28, 2022
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Luciana Corrêa
Grantee:Flávia Cristina Rosin Prado
Home Institution: Faculdade de Odontologia (FO). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Chemotherapy agents 5- fluorouracil (5-FU), methotrexate (MTX) and melphalan are widely used in the treatment of malignant neoplasms and hematopoietic stem cell transplantation conditioning. These agents, however, induce intense production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which in the oral mucosa, can lead to the development of oral mucositis. Oxidative stress can trigger a DNA damage response (DDR), which includes mechanisms such as DNA repair, cell cycle arrest, and induction of apoptosis or cellular senescence. Low level laser therapy has been used for the prevention and treatment of oral mucositis, however, the effects of this therapy on oxidative stress and DDR in cells submitted prior to chemotherapy treatment is still unknown. The aim of this study is to expose oral keratinocytes to chemotherapy agents 5-FU, melphalan and MTX and to analyze the effects of low level laser therapy with different energy parameters (0,2J - 6,6J/cm2; 0,4J - 13,3J/cm2; 1J - 33,3J/cm2, 2J - 66,6J/cm2) on the production of ROS, DNA fragmentation, base oxidation, and expression of antioxidant proteins and related to DDR (³-H2AX, ERCC1, OGG1, ATM and p53). It is also intended to verify the effect of low level laser therapy on the progression of cell cycle. It is expected to elucidate whether low level laser therapy may reduce de effects of chemotherapy agents on the DNA of normal oral keratinocytes, as well as energy range is most suitable for this purpose.