Nucleotide Excision Repair Is Reduced in Oral Epithelial Tissues Compared with Skin^‡

Abstract

Ultraviolet radiation (UVR) exposure to internal tissues for diagnostic, therapeutic and cosmetic procedures has increased dramatically over the past decade. The greatest increase in UVR exposure of internal tissues occurs in the cosmetic industry where it is combined with oxidizing agents for teeth whitening, often in conjunction with indoor tanning. To address potential carcinogenic risks of these procedures, we analyzed the formation and repair of the DNA photoproducts associated with the signature mutations of UVR. Radioimmunoassay was used to quantify the induction and repair of cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone photoproducts in DNA purified from three reconstructed tissues, EpiDerm™, EpiGingival™, and EpiOral™ (MatTek Corp.). We observed comparable levels of DNA damage in all tissues immediately after UVR exposure. In contrast, repair was significantly reduced in both oral tissues compared to EpiDerm™. Our data suggest that UVR exposure of oral tissues can result in accumulation of DNA damage and increase the risk for carcinoma and melanoma of the mouth. Because NER is a broad-spectrum defense against DNA damage caused by a variety of agents in addition to UVR, our data suggest that the relatively low NER efficiency observed in oral tissues may have wide-ranging consequences in this highly exposed environment.

UV Radiation Increases Carcinogenic Risks for Oral Tissues Compared to Skin

“…Using the slopes of the lines from the initial CPD damage and after 24 h to calculate the repair rates, we found similar CPD repair rates between EpiDerm TM (~42%) and EpiGingival TM (~50%) tissue cells using our fluorescent procedure and analysis method, but significantly different CPD repair rates between EpiDerm TM (~42%) and EpiOral (~17%) tissue cells (P < 0.05). Radioimmunoassay agrees with our significant repair rate for EpiDerm TM (~59%) and our insignificant repair rate for oral cells (~0%), but gave a somewhat reduced repair rate for gingival cells [~28%; (33)]. The P-values indicate significant repair occurs in skin (P = 0.01) and gingival tissues (P = 0.04) after 24 h, but not in oral tissues (P = 0.17).…”

“…We found oral tissue cells have a significant reduction in their ability to repair CPD DNA damage compared with skin tissue cells using two different quantification approaches, our immunohistochemical fluorescent assay of fixed tissues shown here [ Fig. 2 and Table 1; (29)] and the established radioimmunoassay of DNA extracts, which unlike our fluorescent procedure includes the CPD in the differentiating cells and cornified layers of the skin and gingival tissues (33). Nevertheless, both approaches found oral tissue cells cannot repair CPD efficiently compared with skin tissue cells.…”

UVB‐Induced Inflammatory Cytokine Release, DNA Damage and Apoptosis of Human Oral Compared with Skin Tissue Equivalents

“…We previously found a UVB dose–response relationship for DNA damage in 3D‐equivalent models of human skin (EpiDerm™), gingival (EpiGingival™) and oral (EpiOral™) tissues using radioimmunoassay . Here, we show the fluorescent analysis of DNA damage in the form of CPD after the tissues received ca 2 MED (660 Jm −2 ) of UVB radiation (Fig.…”

“…Nevertheless, significant carcinogenic risks may not exist for all UV wavelengths or for all internal tissues because another study using a UVB-emitting medical device to treat allergic rhinitis by causing immune suppression (24,25) revealed that nasal and skin cells have similar DNA damage repair rates (26). However, our earlier studies using radioimmunoassay showed UVB induces a dosedependent increase in the number of cyclobutane pyrimidine dimmers (CPD) in human skin, gingival and oral tissue 3Dequivalents that oral tissue cells cannot efficiently repair compared with skin tissue cells (27). We found that the oral tissue cells have a significant reduction in their ability to repair UVBinduced DNA damage (both 6-4 photoproducts and CPD) compared with skin tissue.…”

Risk of a Second Primary Cancer after Non-melanoma Skin Cancer in White Men and Women: A Prospective Cohort Study

“…For example, relatively low NER efficiency was observed in oral tissues [35]. Both rapidly proliferating tissues (e.g., kidney) and slowly proliferating tissues (e.g., lung) exhibit higher demand for NER capacity upon stimulation to proliferation [36].…”