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Archives of Oral Biology

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

Abstract

Objective

To evaluate the oxidative DNA impairment, through 8-hydroxy-ii′-deoxyguanosine (eight-OHdG), and its repair by base excision repair pathway [Redox factor-1 (Ref-1); X-ray Repair Cantankerous Complementing-i (XRCC-1)] in dissimilar epithelial dysplasia degrees in oral leukoplakia.

Design

Forty-four cases of oral leukoplakia and 10 normal oral mucosa were quantified for 8-OHdG, Ref-ane, and XRCC-ane through immunohistochemistry.

Results

Cytoplasmic viii-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 viii-OHdG expression increase was observed between normal oral mucosa and epithelial dysplasia (p < 0.05). Nuclear Ref-one expression was significantly lower (p < 0.01) in non-dysplasia/mild dysplasia, while its cytoplasmic expression was significantly higher in non-dysplasia/balmy dysplasia compared to moderate/astringent dysplasia and normal oral mucosa (p = 0.03; p < 0.0001, respectively). A significantly higher cytoplasmic XRCC-i 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

viii-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 unlike roles co-ordinate to the caste of epithelial dysplasia. Cytoplasmic XRCC-1 expression indicates a possible failure of the Deoxyribonucleic acid repair machinery and occurs in early morphological stages of epithelial dysplasia.

Introduction

Oral potentially malignant disorders are a group of oral conditions and lesions that tin can precede the oral squamous cell carcinoma, which is associated with high-rate mortality. Among oral potentially cancerous disorders, oral leukoplakia is the most common and shows a worldwide incidence between 2% and 4% (Rubert et al., 2020, Villa et al., 2019). Clinically, it is presented as a predominantly white plaque and tin can be subdivided as a thin and flat homogenous lesion, or non-homogenous when it exhibits mixed red-and-white color or verrucous surface. Also, it may vary from non-dysplastic hyperkeratosis to various degrees of epithelial dysplasia in the microscopic examination (Carrard and van der Waal, 2018, van der Waal, 2019).

Several environmental, habit, and clinical features influence the presence and the severity of epithelial dysplasia, which is an important predictive factor in the malignant transformation of oral leukoplakia. Besides, imbalances in the epithelial cellular homeostasis, tin contribute to the initiation, promotion, and progression of oral squamous jail cell carcinoma (Carrard and van der Waal, 2018, Jayasooriya et al., 2020, Kesarwala et al., 2016). Oxidative stress is characterized every bit an imbalance betwixt the production of costless radicals and the cellular antioxidant response, which tin can lead to undesirable impairment to macromolecules, such as Deoxyribonucleic acid. Of the four DNA bases, guanine is the most sensitive to this procedure, being eight-hydroxy-2′-deoxyguanosine (8-OHdG) a product of its oxidative impairment (García-Guede et al., 2020, He et al., 2014, Mazlumoglu et al., 2017, Sardaro et al., 2019).

Base modifications in the DNA caused by oxidative stress, can exist repaired through the base excision repair (BER) pathway. In this pathway, 8-OHdG is excised leaving an apurinic site where intermediates, such as the Redox gene-ane (Ref-1) and X-Ray Repair Cross Complementing-1 (XRCC-i), acts in the DNA repair process. However, failures in the removal and replacement machinery as well as the accumulation of these modified bases may crusade the formation of a malignant cell phenotype (Parsons et al., 2010, Poetsch, 2020, Wallace et al., 2012). Likewise, previous studies take shown the high levels of 8-OHdG are associated to the oral squamous jail cell carcinoma, suggesting that it plays an important part in the germination of this malignant neoplasm (He et al., 2014, Kaur et al., 2016, Mazlumoglu et al., 2017, Yoshifuku et al., 2018). In this context, given the oxidative Dna harm participation in carcinogenesis, this study investigated the association between the viii-OHdG, Ref-i, and XRCC-ane immunoexpression and the clinicopathological features of a case series of oral leukoplakia.

Department snippets

Report design

The present written report was approved by the Federal University of Rio Grande do Norte Research Ethics Committee (Approving No. 2.052.349). This was a prospective and longitudinal study with 44 patients clinically diagnosed with oral leukoplakia at the Oral Diagnostic Service of the Federal Academy of Rio Grande exercise Norte (Natal, RN, Brazil) from January 2007 to June 2019. Information technology was included in this report cases of oral leukoplakia which diagnosed was based on clinical diagnostic features with the

Clinicopathological data

It was observed that oral leukoplakias more often than not affected female person (northward = 29; 65.9%) and the patients exhibited a mean age of 60 ± xiii.3 years-old (range: 29 – 85 years-one-time). Nineteen patients were white (43.2%) and half dozen were black (22.seven%). The natural language was the most affected anatomic site (n = 14; 31.8%) followed past alveolar ridge (north = 10; 22.7%), buccal mucosa (northward = ix; 20.five%), retromolar trigone (n = 4; 9.1%), labial mucosa (n = iv; ix.i%), and palate (north = 3; half dozen.8%). Most cases presented homogeneous lesions

Word

Reactive oxygen species are highly reactive cellular biochemical products that naturally arise from normal physiological processes. However, its elevated intracellular levels cause harmful oxidative stress, which contributes to diverse oral diseases, such as cancer (Kesarwala et al., 2016, Sardaro et al., 2019). To the best of our knowledge, this is the first written report to investigate the expression of 8-OHdG as well as DNA base excision repair proteins Ref-1 and XRCC-1 in oral leukoplakia. We

Writer contributions argument

All authors have essentially contributed to this research. Caio César da Silva Barros performed the clinical follow-upwards, analyzed the information, and wrote the paper. Roseana de Almeida Freitas performed the morphological analysis, performed the immunohistochemical analysis, and reviewed the paper for of import intellectual content. Márcia Cristina da Costa Miguel performed the morphological analysis, conceived and designed the study, and reviewed the paper for important intellectual content. Éricka

Conflict of interest

The authors declare no conflict of interest.

Acknowledgement

This study was supported by the Brazilian National Quango for Scientific and Technological Development (CNPq) and the Coordination for the Improvement of College Education Personnel (CAPES).

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