Different involvement of radical species in irradiated and bystander cells.

PURPOSE: To examine whether nitric oxide (NO) and other radical species are involved in radiation-induced bystander effects in normal human fibroblasts. MATERIALS AND METHODS: Bystander effects were modeled by co-culture of non-irradiated cells with X-irradiated cells, and induction levels of micronuclei in co-cultured non-irradiated cells were examined. Three types of radical scavenger, 2-(4-carboxyphenyl)-4,4,5,5- tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), dimethylsulfoxide (DMSO) and ascorbic acid phosphoric ester magnesium salt (APM), were used to discover which types of radicals are involved in bystander responses. RESULTS: When irradiated cells were treated with c-PTIO, known to be an NO scavenger, the induction of micronuclei in non-irradiated bystander cells was suppressed. On the other hand, bystander effects were most effectively suppressed when non-irradiated bystander cells were treated with ascorbic acid, known to be a scavenger of long lived radicals. CONCLUSION: These results suggest that NO participates in bystander signal formation in irradiated cells but not in bystander cells that are receiving bystander signals.