Melanocytes are selectively vulnerable to UVA-mediated bystander oxidative signaling.

Long-wave UVA is the major component of terrestrial UV radiation and is also the predominant constituent of indoor sunlamps, both of which have been shown to increase cutaneous melanoma risk. Using a two-chamber model, we show that UVA-exposed target cells induce intercellular oxidative signaling to non-irradiated bystander cells. This UVA-mediated bystander stress is observed between all three cutaneous cell types (i.e., keratinocytes, melanocytes, and fibroblasts). Significantly, melanocytes appear to be more resistant to direct UVA effects compared with keratinocytes and fibroblasts, although melanocytes are also more susceptible to bystander oxidative signaling. The extensive intercellular flux of oxidative species has not been previously appreciated and could possibly contribute to the observed cancer risk associated with prolonged UVA exposure.