title: Molecular response of nasal mucosa to therapeutic exposure to broad-band ultraviolet radiation.
abstract: 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.
authors.affiliation: Department of Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA. dmitchel@mdanderson.org
authors.forename: David
authors.initials: D
authors.lastname: Mitchell
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Paniker
authors.forename: Guillermo
authors.initials: G
authors.lastname: Sanchez
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Bella
authors.forename: Edina
authors.initials: E
authors.lastname: Garaczi
authors.forename: Marta
authors.initials: M
authors.lastname: Szell
authors.forename: Qutayba
authors.initials: Q
authors.lastname: Hamid
authors.forename: Lajos
authors.initials: L
authors.lastname: Kemeny
authors.forename: Andrea
authors.initials: A
authors.lastname: Koreck
mesh_terms: D004247:DNA / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D009297:Nasal Mucosa / Q000502:physiology / Q000528:radiation effects*; D010789:Phototherapy; D006255:Rhinitis, Allergic, Seasonal / Q000532:radiotherapy; D012867:Skin / Q000378:metabolism / Q000528:radiation effects; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods; D014466:Ultraviolet Rays
chemical_list: D004247:DNA