Abstract
Radiation induced bystander effect (RIBE) increases the probability of cellular response and therefore has important implications for cancer risk assessment following low dose irradiation and also for the likelihood of secondary cancers after radiotherapy. With a series of experiments of treating cells with NO inhibitor, TGF-beta1, or anti- TGF-beta1, the present study found that, when a fraction of glioma cells T98G were individually irradiated with a very low dose of helium ions, as a downstream product of irradiation-induced nitric oxide (NO), TGF-beta1 was released to the conditioned medium and caused further DNA damage in the bystander cells of either T98G or primary fibroblasts AG01522 co-cultured with irradiated T98G cells by inducing NO and ROS in the nonirradiated T98G and AG01522 cells, respectively. In addition, as an early response to bystander signal factors, calcium flux could be quickly triggered in the nonirradiated cells after receiving the conditioned medium from the glioma cells irradiated with a very low dose of helium ions. This calcium flux response could further induce micronucleus formation in the bystander cells through a pathway related to NO and ROS. In summary, NO, ROS, TGF-beta1 and calcium flux made up of a network of the bystander signaling factors.
