Effect of EGFR mutation on radiation-induced DNA repair in pulmonary adenocarcinoma cells / 中华放射医学与防护杂志

ABSTRACT

Objective To observe the effect of EGFR mutation on radiation induced DNA repair in pulmonary adenocarcinoma ceils.Methods A549 cells with wild-type EGFR and H1975 cells with mutated-type of EGFR were irradiated by 4 Gy of 6 MV X-rays.After irradiation,the formation of nuclear γ-H2AX foci was assayed with immunostaining method,the level of DNA-PKcs-EGFR interaction was detected with coimmunoprecipitation,and nuclear RAD51 expression and EGFR nuclear translocation were detected using Western blot.Results DNA repair in the H1975 cells was significantly lower than that in A549 cells.In the irradiated H1975 cells,there was no EGFR translocation with further nuclear DNA-PKcs binding,and the expression of nucleus RAD51 was not altered.But in the irradiated A549 cells,EGFRDNA-PKcs interaction and nucleus RAD51 were increased.Conclusions Lung adenocarcinoma cell line with mutations in the tyrosine kinase domain (TKD) of EGFR exhibits a high radiosensitivity due to the reduction of the non-homologous end-joining (NHEJ) and homologous recombination (HR) DNA DSB repair kinetics.