Abstract
This study aims to investigate the medium-mediated bystander effect and the role of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) in the bystander effect. The induction of chromosomal aberrations was observed in recipient normal human fibroblast cells treated with conditioned medium that was harvested from donor fibroblasts exposed to low-linear energy transfer (LET) X-rays and high-LET heavy ions. The recipient cells were treated for 12 h with conditioned medium, which were harvested from donor cells at 24 h after exposure to 10 Gy of 30 kVp soft X-rays and 20Ne ions (437 keV/micro-m), followed by analyses of chromosome aberrations in recipient cells with premature chromosome condensation methods. To examine the role of DNA-PKcs and nitric oxide (NO), cells were treated with its inhibitor LY294002 (LY) and its scavenger (c-PTIO), respectively. Increased frequency of chromosomal aberrations in recipient cells treated with conditioned medium from irradiated but not from un-irradiated donor cells was observed which was independent of radiation type. Bystander induction of chromosomal aberrations in recipient cells was mitigated when donor cells were treated with LY before irradiation and with c-PTIO after irradiation, and was enhanced when recipient cells were treated with LY before treatment of recipient cells with conditioned medium from irradiated donor cells. Irradiated normal human cells secrete NO and other molecules which in turn transmit radiation signals to un-irradiated bystander cells.
