Effects of ionizing radiation on cell fate and non-ionizing radiation on stress response in human neuronal cells

초록

Part I: Loss of the tumor suppressor PTEN has frequently been observed in human gliomas, conferring AKT activation and resistance to ionizing radiation (IR) and drug treatments. Recent reports have shown that PTEN loss or AKT activation induces premature senescence, but many details regarding this effect remain obscure. In this study, we tested whether the status of PTEN determined cell fate by examining PTEN-deficient U87, U251, and U373 and PTEN-proficient LN18 and LN428 glioma cells after exposure to IR. These cells exhibited different cellular responses, senescence or apoptosis, depending on PTEN status. We further observed that PTEN-deficient U87 cells with high levels of both AKT activation and intracellular reactive oxygen species (ROS) underwent senescence, whereas PTEN-proficient LN18 cells entered apoptosis. ROS were indispensible for inducing senescence in PTEN-deficient cells, but not for apoptosis in PTEN-proficient cells. Furthermore, transfection with wild type PTEN or AKT siRNA induced a change from premature senescence to apoptosis, and depletion of p53 or p21 prevented IR-induced premature senescence, in U87 cells. Our data indicate that PTEN acts as a pivotal determinant of cell fate regarding senescence and apoptosis in IR-exposed glioma cells. We conclude that premature senescence could play a compensatory role for apoptosis in the absence of the tumor suppressor PTEN through the AKT/ROS/p53/p21 signaling pathway. Part II: As a large number of individuals have been exposed to the radiofrequency (RF) signals from cellular phones, social concerns regarding in possible biological effects of radiofrequency radiation emitted from cellular phones on human health have been increased. The objective of the study was to investigate the effects of the combined RF radiation (837 MHz CDMA plus 1,950 MHz WCDMA) signal on levels of intracellular reactive oxygen species (ROS) in neuronal cells. Exposure of the combined RF signal was conducted at specific abs