DNA damage through oxidative stress is an important event in oral leukoplakia

• Published in: Archives of oral biology Vol. 135; p. 105359
• Main Authors: Barros, Caio César da Silva, Freitas, Roseana de Almeida, Miguel, Márcia Cristina da Costa, Dantas da Silveira, Éricka Janine
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-03-2022
• Subjects: DNA Damage; DNA repair; Humans; Immunohistochemistry; Leukoplakia, Oral - metabolism; Mouth Mucosa - metabolism; Oral leukoplakia; Oxidative Stress; Precancerous Conditions - metabolism; Oxidative stress; XRCC-1; Ref-1; Oral leukoplakia; DNA repair; BER; 8-OHdG
• ISSN: 0003-9969; 1879-1506
• DOI: 10.1016/j.archoralbio.2022.105359

To evaluate the oxidative DNA damage, through 8-hydroxy-2′-deoxyguanosine (8-OHdG), and its repair by base excision repair pathway [Redox factor-1 (Ref-1); X-ray Repair Cross Complementing-1 (XRCC-1)] in different epithelial dysplasia degrees in oral leukoplakia.
Forty-four cases of oral leukoplakia and 10 normal oral mucosa were quantified for 8-OHdG, Ref-1, and XRCC-1 through immunohistochemistry.
Cytoplasmic 8-OHdG and nuclear XRCC-1 were significantly associated with multiple synchronous lesions (p = 0.048; p = 0.034, respectively). Nuclear Ref-1 was significantly associated with oral leukoplakia on the tongue (p = 0.027). A significantly gradual cytoplasmic 8-OHdG expression increase was observed between normal oral mucosa and epithelial dysplasia (p < 0.05). Nuclear Ref-1 expression was significantly lower (p < 0.01) in non-dysplasia/mild dysplasia, while its cytoplasmic expression was significantly higher in non-dysplasia/mild dysplasia compared to moderate/severe dysplasia and normal oral mucosa (p = 0.03; p < 0.0001, respectively). A significantly higher cytoplasmic XRCC-1 expression was observed in non-dysplasia/mild and moderate/severe dysplasia compared to normal oral mucosa (p < 0.0001; p < 0.0001, respectively). All epithelial dysplasia degrees showed a correlation between nuclear and cytoplasmic expression of these proteins (p < 0.05).
8-OHdG formation may not play a role in the development of multiple synchronous oral leukoplakias. However, it is related to the severity of the epithelial dysplasia. The subcellular level of Ref-1 implies different roles according to the degree of epithelial dysplasia. Cytoplasmic XRCC-1 expression indicates a possible failure of the DNA repair mechanism and occurs in early morphological stages of epithelial dysplasia.
•DNA damage was related with the anatomic site of the oral leukoplakia.•DNA damage was related to oral leukoplakia multiple synchronous lesions.•Oxidative stress may be related with the progression of the epithelial dysplasia.•DNA repair maintain mitochondrial and genetic stability in epithelial dysplasia.•Epithelial dysplasia may exhibit a failure in the DNA repair process.