Mitchell1, D., Paniker1, L., Sanchez1, G., Bella2, Z., Garaczi3, E., Szell4, M., Hamid5, Q., Kemeny3,4, L., and Koreck3,6, A. 1Department of Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, Texas, USA. 2Department of Otolaryngology, Head and Neck Surgery, University of Szeged, Hungary. 3Department of Dermatology and Allergology, University of Szeged, Hungary. 4Dermatological Research Group of the Hungarian Academy of Sciences, Szeged, Hungary. 5Meakins-Christie Laboratories, McGill University , Montreal, Quebec, Canada. 6Department of Immunology, Victor Babes University, Timisoara, Romania.

This study by researchers at MD Anderson Cancer Center (USA), the University of Szeged (Hungary), the Hungarian Academy of Sciences (Hungary), McGill University (Canada) and Victor Babes University (Romania) demonstrated that MatTek’s EpiAirway in vitro human tracheal/bronchial tissue equivalent and EpiDerm in vitro human skin tissue equivalent can be used to model the UV-induced DNA damage response of human respiratory epithelia. Ultraviolet radiation (UVR) phototherapy is a promising new treatment for inflammatory airway diseases. However, the potential carcinogenic risks associated with this treatment are not well understood. UV-specific DNA photoproducts were used as biomarkers to address this issue. Radioimmunoassay was used to quantify cyclobutane pyrimidine dimers (CPDs) and (6-4) photoproducts in DNA purified from two milieus: nasal mucosa samples from subjects exposed to intranasal phototherapy and human airway (EpiAirway™) and human skin (EpiDerm™) tissue models. Immunohistochemistry was used to detect CPD formation and persistence in human nasal biopsies and human tissue models. In subjects exposed to broadband ultraviolet radiation, DNA damage frequencies were determined prior to as well as immediately after treatment and at increasing times post-treatment. We observed significant levels of DNA damage immediately after treatment and efficient removal of the damage within a few days. No residual damage was observed in human subjects exposed to multiple UVB treatments several weeks after the last treatment. To better understand the molecular response of the nasal epithelium to DNA damage, parallel experiments were conducted in EpiAirway and EpiDerm model systems. Repair rates in these two tissues were very similar and comparable to that observed in human skin. The data suggest that the UV-induced DNA damage response of respiratory epithelia is very similar to that of the human epidermis and that nasal mucosa is able to efficiently repair UVB induced DNA damage.


Biomarker, Biomarkers, Cyclobutane pyrimidine dimers (CPD), DNA damage, DNA photoproducts, DNA repair, EpiAirway, EpiDerm, Intranasal phototherapy, Nasal mucosa, Nucleotide excision repair, Photoproducts, Phototherapy, Pyrimidine(6-4)pyrimidone photoproduct, Rhinophototherapy, UV-induced DNA damage, Ultraviolet radiation

Materials Tested

25 nm radiation , 313 nm radiation, Broad-band UV light, Broad-band UVC, UVC

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