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Defective repair of UV-induced DNA damage in cultured primary skin fibroblasts from Saudi thyroid cancer patients.
Artigo em Inglês | IMSEAR | ID: sea-37940
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.
Assuntos
Texto completo: DisponíveL Índice: IMSEAR (Sudeste Asiático) Assunto principal: Tolerância a Radiação / Valores de Referência / Arábia Saudita / Pele / Raios Ultravioleta / Humanos / Neoplasias da Glândula Tireoide / Immunoblotting / Estudos de Casos e Controles / Células Cultivadas Tipo de estudo: Estudo diagnóstico / Estudo observacional País/Região como assunto: Ásia Idioma: Inglês Ano de publicação: 2004 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: IMSEAR (Sudeste Asiático) Assunto principal: Tolerância a Radiação / Valores de Referência / Arábia Saudita / Pele / Raios Ultravioleta / Humanos / Neoplasias da Glândula Tireoide / Immunoblotting / Estudos de Casos e Controles / Células Cultivadas Tipo de estudo: Estudo diagnóstico / Estudo observacional País/Região como assunto: Ásia Idioma: Inglês Ano de publicação: 2004 Tipo de documento: Artigo