title: Defective repair of UV-induced DNA damage in cultured primary skin fibroblasts from Saudi thyroid cancer patients.
abstract: This study was conducted to examine the sensitivity of primary skin fibroblasts from Saudi thyroid cancer (TC) patients to ultraviolet (UV) irradiation. Cell survival was studied by a colony forming assay and DNA repair defects with a host cell reactivation (HCR) assay using UV-irradiated Herpes Simplex Virus (HSV). In addition, p53 gene expression was examined in the same TC cells exhibiting enhanced radiosensitivity. Skin fibroblasts from TC patients (n=4) showed significantly enhanced sensitivity to UV radiation. The average UV dose to reduce survival to 37% of the initial survival (D(37)) value (in Jm(-2)) for fibroblasts from TC patients was 4.6 (3.7-5.6) compared to 7.3 (6.3-8.3) for healthy individuals (n=3). UV-sensitive xeroderma pigmentosum (XP) cells, which were used as positive control, were found to be extremely sensitive with a D(37) value of 0.6 Jm(-2). In a host cell reactivation assay, UV-irradiated HSV was tested for its plaque-forming ability (PFA), by plating infected fibroblasts from TC patients (used as host cells) on African Green Monkey (Vero) kidney cells to form plaques. A significant reduction in the PFA of the UV-irradiated virus (about three fold) on TC cells compared to fibroblasts from the healthy subjects was seen, suggesting a DNA-repair deficiency in the primary fibroblasts of the TC patients. Furthermore, no significant accumulation in radiation-induced p53 expression was observed in cells from the TC patients. Our results, based on a relatively small group of subjects, indicate that Saudi TC patients primary fibroblasts (non-cancerous in nature) may be carriers of cancer-susceptible gene(s) arising from defective DNA repair/processing. These results warrant a larger study to investigate the role of UV-induced bulky DNA damage in thyroid cancer susceptibility.
authors.affiliation: Biological and Medical Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Fahad M
authors.initials: FM
authors.lastname: Al-Khodairy
authors.forename: Mohammed
authors.initials: M
authors.lastname: Kunhi
authors.forename: Yunus M
authors.initials: YM
authors.lastname: Siddiqui
authors.forename: Jamal M
authors.initials: JM
authors.lastname: Arif
authors.forename: Mohammed N
authors.initials: MN
authors.lastname: Al-Ahdal
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Hannan
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D016022:Case-Control Studies; D002478:Cells, Cultured; D004260:DNA Repair / Q000235:genetics* / Q000528:radiation effects*; D005347:Fibroblasts / Q000502:physiology* / Q000528:radiation effects*; D016158:Genes, p53; D006579:Heterozygote; D006801:Humans; D015151:Immunoblotting; D011336:Probability; D011836:Radiation Tolerance; D012016:Reference Values; D012494:Sampling Studies; D012529:Saudi Arabia; D012680:Sensitivity and Specificity; D012867:Skin / Q000166:cytology; D013964:Thyroid Neoplasms / Q000235:genetics*; D014466:Ultraviolet Rays / Q000009:adverse effects*