Bystander Effect in Lymphoma Cells Vicinal to Irradiated Neoplastic Epithelial Cells: Nitric Oxide Is Involved

Evidence has been accumulated for attached cells demonstrating that nonirradiated cells can have a response to the ionization events delivered to their neighbors. In the present study, we first investigated the bystander responses between suspension and neoplastic cells by coculturing L5178Y (LY) cells with human salivary gland (HSG) cells that had been irradiated with either 290 MeV/u carbon ions or X-rays. After this coculture, the survival of nonirradiated recipient LY cells showed dichotomous responses to the irradiation dose delivered to HSG cells. Apoptosis and necrosis were also produced in a 48 h subculture of the recipient LY cells, and their yield increased, but then had a tendency to decrease when the irradiation dose increased. Treatment of cells with PTIO, a nitric oxide specific scavenger, diminished apoptosis and necrosis of the recipient LY cells to the control level. As an oxidization product of NO, nitrite was detected in the coculture medium and its time course corresponded well to the decrease of the viability of irradiated HSG cells. Moreover, the relationship of the survival and the apoptotic and necrotic production of the recipient LY cells to the nitrite concentration followed a linear-quadratic model. The present findings of NO being involved in the radiation-induced bystander effect may have significance in terms of radiotherapy.