Nitric oxide-mediated bystander effect induced by heavy-ions in human salivary gland tumour cells

PURPOSE: To investigate the signal factor and its function in the medium-mediated bystander effect during heavy-ion irradiation of human salivary gland (HSG) neoplastic cells. MATERIALS AND METHODS: Unirradiated recipient HSG cells were co-cultivated with HSG donor cells irradiated with 290 MeV/u carbon beams having different LET values. Cell proliferation and micronucleus (MN) induction in recipient cells with and without treatment of a NO scavenger (PTIO) were measured and the concentration of nitrite in the co-culture medium was detected. As a direct control, the effects of a nitric oxide (NO) generator (sper/NO) on cell proliferation and MN induction were also examined. RESULTS: Increases in cell proliferation and MN induction were found in the recipient HSG cells as a result of co-culturing and cell proliferation was obviously enhanced during a further subculture. In comparison with 13keV/microm, 100keV/microm carbon-ion irradiation was found to be a more efficient inducer of the medium-mediated bystander effect. The treatment of cells by PTIO resulted in elimination of such effects, which supports a role for NO in the medium-mediated bystander effect. As an oxidization product of NO, nitrite was detected in the co-culture medium, and the dose-response for its concentration was similar to that of cell proliferation and MN induction in the recipient cells. When the HSG cells were treated by sper/NO with a concentration of less than 20 microM cell proliferation was enhanced, whereas MN increased along with sper/NO concentration. CONCLUSION: NO participated in the medium-mediated bystander effects on cell proliferation and MN induction, depending on the LET of irradiation.