COLON CANCER CELLULAR MODEL FOR STUDYING RADIORESISTANCE MODULATION

CERDA, MARÍA BELÉN; BRACALENTE, CANDELARIA; IBAÑEZ, IRENE; TROPPER, IVANNA; MOLINARI, BEATRIZ L.; PODHAJCER, OSAVALDO; DURÁN, HEBE; POLICASTRO, LUCÍA

Puerto Madryn, Chubut, Argentina

Congreso; XLVI Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology; 2010

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Tumor radioresistance is one of the main causes that lead toradiotherapy failure. The aim of this study was to evaluate theintrinsic radiosensitivity of colon human cancer cell lines to furtherstudy the modulation of radiation response by silencingradioresistant associated genes. Survival curves and DNA damageinduced by gamma radiation were evaluated in HT-29, Caco-2 andLoVo cells. Survival curves were fitted to the linear-quadraticmodel S=exp-[(alpha)D+(Beta)D square], showing significant increasing values of alpha parameter: HT-29 (alpha=0.47+/-0.07) Caco-2 (alpha=0.86+/-0.17) and LoVo (alpha= 1.41+/-0.13) and the loss of the quadratic component (Beta=0) for this last cell line. To evaluate DNA damage and repair induced by gamma radiation (2 Gy), phosphorylated histone H2AX (gamma H2AX) was determined by immunohistochemistry as a measure of DNA double strand breaks (DSBs) at 0.5 and 6 h post-irradiation. The number of foci per nucleus decreased significantly at 6 h post-irradiation: 65% for HT-29, 40% for Caco-2 and 20% for LoVo cells. The evaluation of initial damage by analysing foci size at 30min post-irradiation showed a significant increase of 33% in HT-29,66% in Caco-2 and 132% in LoVo.These results show that these cells have different degree ofradioresistance to gamma radiation (HT-29>Caco-2>LoVo) andthey may be a useful model to study the modulation ofradioresistance. Publicado en BIOCELL 2010, Vol. 34 (Suppl.): 63