Abstract
There has recently been an upsurge of interest in ionizing radiation-induced bystander effects. However, its dependence upon linear energy transfer (LET) remains to be elucidated. Utilizing our systems of collimated heavy-ion microbeams available at Takasaki Ion Accelerators for Advanced Radiation Application (TIARA) of JAEA, the current investigation here aims to characterize bystander killing by three types of heavy ions with differing LET in confluent density-inhibited normal human fibroblast AG01522 cells under conditions that intercellular interactions are facilitated. Clonogenic survival analyses revealed that targeted irradiation of a few cells within the whole population of around million cells resulted in nearly 10% loss of clonogenicity, indicating the induction of bystander responses. Besides, apoptosis in the bystander population was detected with TdT-mediated dUTP nick end labeling assay, of which induction peaked at 24 hours post-irradiation. Meanwhile, to an extent similar to bystander apoptosis frequency, apoptotic frequency increased at least up to 72 hours following the random irradiation with 10% survival doses of corresponding broad beams of heavy ions. Our present findings suggest the modal and temporal distinction of cell death between irradiated cells and non-irradiated bystanders. Moreover, very little difference in these bystander responses was found among number of heavy ions targeted (1, 5, 10 ions), and between LET values (103, 294, 375 keV/μm) as well.
