Presentation Differential processing of low and high LET radiation induced DNA damage: Investigation of switch from ATM to ATR signaling(15J386)

XUE, Lian  ,  Yu, Dong  ,  Yajima, Hirohiko  ,  Furusawa, Yoshiya  ,  Liu, Cuihua  ,  Fujimori, Akira  ,  Wang, Bing

In the past HIMAC experiments, we proved that ATR pathway was more efficiently activated by heavy ion beams compared with X rays. As ATR pathway is overactivated in hepatocellular carcinoma, we wanted further to explore whether inhibition of ATR pathway can exhibit radiosensitive effects under different types of radiation (low and high LETs) in hepatocellular carcinoma. First of all, MTT assay was carried out to find out the dose-effect relationship between the concentrations of ATR inhibitor, VE-821 and the cellular viability of HepG2 cells, which were treated with VE-821 of different doses for three days. As Fig. 1 indicated, the cellular viability decreased with the increase of doses, and there was more than 90% of viability in HepG2 cells under exposure to VE-821 of doses lower than 2 μM. The expression of phosphorus ATR (T1989) and CHK1 (S345), which can both reflect the activation of ATR pathway were detected with Western blot. As figure 2 showed that there was a dose-effect relationship between of different doses of VE-821 and the activation of ATR pathway as early as 2 h post IR. VE-821 was pretreated 0.5 h prior to exposure to 6 Gy of X ray. The doses of both 1 and 2 μM were used to find out whether there’s radiosensitive effects for VE-821 by colony forming assay. Firstly, the colony forming ability of HepG2 cells was inhibited under the treatment of VE-821, with the survival fraction of about 60% and 20% for the concentrations of 1 and 2 μM respectively. Secondly, there were radiosensitive effects for VE-821 on HepG2 cells.

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