Timeframes of UVA-induced bystander effects in human keratinocytes

The bystander effect is defined as the induction of cellular damage in unirradiated cells, induced by irradiated cells in the surrounding area. Our laboratory has previously identified that an environmentally relevant dose of UVA is able to induce the effect in human keratinocytes and fibroblasts, seen as reduced clonogenic survival. Here we report on our investigations into the periods over which the bystander signals are released by the irradiated cells and for how long unirradiated cells need to be exposed to them for the effect to be induced. Using a coincubation system we have identified that irradiated cells do not release the signals immediately following irradiation but have a time lag of over 24 h before levels are sufficient to induce the effect, with the signals being released for a minimum of 3 days following irradiation. We have also found that the recipient cells only require at most 24 h of exposure to these signals for induction of the effect. These data indicate that a single exposure to UVA can exert an effect for several days postirradiation, thus amplifying the deleterious effects of exposure.