The Role of nitric oxide in radiation-induced bystander cell-killing effect

Yokota, Yuichiro; Funayama, Tomoo; Ikeda, Hiroko; Sakashita, Tetsuya; Suzuki, Michiyo; Kobayashi, Yasuhiko

The role of nitric oxide (NO) in bystander effect was investigated. Human fibroblasts were irradiated with -rays (LET: 0.2 keV/m) or carbon-ion beam (108 keV/m), and then, co-cultured with the non-irradiated cells. After 24 h culture, the survival rates of non-irradiated cells and the concentrations of nitrate, an oxide of NO, in the medium were measured. The survival rates of non-irradiated cells decreased in dose-dependent and radiation quality-independent manners. Negative relationships between survival rates and nitrite concentrations existed, indicating the amounts of produced NO are an important determinant of bystander effects. Next, a reagent producing two molecules of NO in a half-life of 100 min was added in the culture medium. After incubation of 24 h the survival rates of treated cells did not decrease, suggesting NO produced intracellularly has an important role to lead the bystander effect but is not the signal molecule for intercellular communication.