DNA damage response signaling in lung adenocarcinoma A549 cells following gamma and carbon beam irradiation

Carbon beams (5.16 MeV/u, LET = 290 keV/μm) are high linear energy transfer (LET) radiation characterized by higher relative biological effectiveness than low LET radiation. The aim of the current study was to determine the signaling differences between γ-rays and carbon ion-irradiation. A549 cells were irradiated with 1 Gy carbon or γ-rays. Carbon beam was found to be three times more cytotoxic than γ-rays despite the fact that the numbers of γ-H2AX foci were same. Percentage of cells showing ATM/ATR foci were more with γ-rays however number of foci per cell were more in case of carbon irradiation. Large BRCA1 foci were found in all carbon irradiated cells unlike γ-rays irradiated cells and prosurvival ERK pathway was activated after γ-rays irradiation but not carbon. The noteworthy finding of this study is the early phase apoptosis induction by carbon ions. In the present study in A549 lung adenocarcinoma, authors conclude that despite activation of same repair molecules such as ATM and BRCA1, differences in low and high LET damage responses might be due to their distinct macromolecular complexes rather than their individual activation and the activation of cytoplasmic pathways such as ERK, whether it applies to all the cell lines need to be further explored.

► Carbon beam induces efficient cell killing in lung carcinoma A549 cells.
► Large BRCA1 foci were found in all carbon irradiated cells.
► Pro-survival ERK pathway was activated after gamma irradiation but not carbon.
► Pro-apoptotic JNK pathway was found to be activated after high LET radiation.
► There was early phase induction of apoptosis by carbon ions.