title: Impaired removal of 8-hydroxydeoxyguanosine induced by UVB radiation in naevoid basal cell carcinoma syndrome cells.
abstract: BACKGROUND
  The naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by tumorigenesis such as multiple basal cell carcinomas, odontogenic keratocysts and developmental abnormalities such as calcified dural folds and rib-anomalies. Recently, it has been shown that ultraviolet (UV) B exposure produced more BCCs in ptch knockout mice than wild mice.
  
  
  OBJECTIVE
  To Investigate the role of UV in development of BCCs in NBCCS, cellular sensitivity to killing by UVB and removal of UVB-induced oxidative DNA damage were examined using fibroblasts derived from patients with NBCCS under physiologically relevant doses of UVB exposure.
  
  
  METHODS
  Three patients with NBCCS, a 59-year-old male patient, an 18-year-old boy and a 13-year-old boy were examined by photobiological analysis. Cellular sensitivity to killing by UVB and UVC and removal of oxidative DNA damage caused by UVB were tested using fibroblasts derived from these patients. We measured cellular 8-hydroxydeoxyguanosine (8-OHdG) after UVB exposure up to 24 h after UVB exposure using high-performance liquid chromatography.
  
  
  RESULTS
  All three cell strains derived from the patients with NBCCS were hypersensitive to killing by UVB (D10: 50-70% of normal) but not by UVC. After UVB exposure, the production of 8-OHdG increased dose dependently up to 3200 J m-2 in both NBCCS cells and normal cells. In normal cells, 8-OHdG after UVB exposure returned to its basal level during 24 h, whereas in NBCCS cells the amount of 8-OHdG after 800 J m-2 of UVB exposure did not return to its basal level even after 24 h. The result indicates the removal of 8-OHdG could be impaired in NBCCS cells. Ability in removal of thymine dimers of NBCCS cells was similar to that of normal cells.
  
  
  CONCLUSIONS
  Hypersensitivity to UVB can be one of the diagnostic tools of NBCCS for those whose clinical features have not yet completed. Hypersensitivity to cell killing and the impairment of removal of 8-OHdG after UVB exposure may play some role in developing BCCs and other tumours in NBCCS.
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. chikako@med.kobe-u.ac.jp
authors.forename: C
authors.initials: C
authors.lastname: Nishigori
authors.forename: Y
authors.initials: Y
authors.lastname: Arima
authors.forename: Y
authors.initials: Y
authors.lastname: Matsumura
authors.forename: M
authors.initials: M
authors.lastname: Matsui
authors.forename: Y
authors.initials: Y
authors.lastname: Miyachi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000293:Adolescent; D000328:Adult; D001478:Basal Cell Nevus Syndrome / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D016923:Cell Death; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D019281:Dimerization; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010787:Photosensitivity Disorders / Q000378:metabolism* / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D013941:Thymine / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D013941:Thymine