Defective repair of UV-induced DNA damage in cultured primary skin fibroblasts from Saudi thyroid cancer patients.
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.
Al-Khodairy
Fahad M
FM
Biological and Medical Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Kunhi
Mohammed
M
Siddiqui
Yunus M
YM
Arif
Jamal M
JM
Al-Ahdal
Mohammed N
MN
Hannan
Mohammed A
MA
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*