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

Objective: 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.
Design: Forty-four cases of oral leukoplakia and 10 normal oral mucosa were quantified for 8-OHdG, Ref-1, and XRCC-1 through immunohistochemistry.
Results: 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).
Conclusions: 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.
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