The purpose of the study was to elucidate the mechanism underlying the enhancement of radiosensitivity to 60Co gamma-irradiation in human hepatoma cell line HepG2 pretreated with gliotoxin. Enhancement of radiotherapy by gliotoxin was investigated in vitro with human hepatoma HepG2 cell line. Apoptosis related proteins were evaluated by Western blotting. Annexin V/PI and reactive oxygen species (ROS) were quantified by Flow Cytometric (FACS) analysis. Gliotoxin (200 ng/ml) combined with radiation (4 Gy) treated cells induced apoptosis. Cells treated with gliotoxin (200 ng/ml) prior to irradiation at 4 Gy induced the expression of bax and nitric oxide (NO). The gliotoxin-irradiated cells also increased caspase-3 activation and ROS. Gadd45a, p38, and nuclear factor kappa B (NFkappaB) activated in irradiated cells was inhibited by Gliotoxin. Specific inhibitors of p38 kinase, SB203580, significantly inhibited NFkappaB activation and increased the cytotoxicity effect in cells exposed to gliotoxin combined with irradiation. However, SB203580 did not suppress the activation of Gadd45a in irradiated cells. Gliotoxin inhibited anti-apoptotic signal pathway involving the activation of Gadd45a-p38-NFkappaB mediated survival pathway that prevent radiation-induced cell death. Therefore, gliotoxin, blocking inflammation pathway and enhancing irradiation-induced apoptosis, is a promising agent to increase the radiotherapy of tumor cells.
An advanced integral pressurized water reactor, SMART (System-Integrated Modular Advanced ReacTor) has been developed by KAERI (Korea Atomic Energy Research and Institute). The purposes of the SMART are sea water desalination and an electricity generation. For the safety evaluation and performance analysis of the SMART, TASS/SMR-S (Transient And Setpoint Simulation/Systemintegrated Modular Reactor) code, has been developed.In this paper, the gap conductance model for the calculation of gap conductance has been validated by using another system code, MARS code, and experimental results. In the validation, the behaviors of fuel temperature and gap width are selected as the major parameters. According to the evaluation results, the TASS/SMR-S code predicts well the behaviors of fuel temperatures and gap width variation, compared to the MARS calculation results and experimental data.
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