Colon cancer cellular model for studying radioresistance modulation

Tumor radioresistance is one of the main causes that lead to radiotherapy failure. The aim of this study was to evaluate the intrinsic radiosensitivity of colon human cancer cell lines to further study the modulation of radiation response by silencing radioresistant associated genes. Survival curves and DNA damage induced by gamma radiation were evaluated in HT-29, Caco-2 and LoVo cells. Survival curves were fitted to the linear-quadratic model S=exp-(αD+βD2), showing significant increasing values of α parameter: HT-29 (α=0.47+/-0.07) Caco-2 (α=0.86+/-0.17) and LoVo (α= 1.41+/-0.13) and the loss of the quadratic component (β=0) for this last cell line. To evaluate DNA damage and repair induced by gamma radiation (2 Gy), phosphorylated histone H2AX (γH2AX) 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 postirradiation: 65% for HT-29, 40% for Caco-2 and 20% for LoVo cells. The evaluation of initial damage by analysing foci size at 30 min 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 of radioresistance to gamma radiation (HT-29>Caco-2>LoVo) and they may be a useful model to study the modulation of radioresistance. (authors)