Thermal injury causes DNA damage and lethality in unheated surrounding cells: active thermal bystander effect

Direct heat exposure to cells causes protein degradation and DNA damage, which can lead to genetic alteration and cell death, but little is known about heat-induced effects on the surrounding tissue. After burns or laser surgery, loss of viability in the surrounding tissue has been explained by a temperature gradient due to heat diffusion. This study shows that, in the absence of any direct heating, heat diffusion, or cell-to-cell contact, "bystander" cells that share the medium with heat-exposed cells exhibit DNA damage, apoptosis, and loss of viability. We coin this phenomenon "active thermal bystander effect" (ATBE). Significant ATBE was induced by fibroblasts exposed for 10 minutes to a temperature range of 44-50 degrees C (all P<0.011). The ATBE was not induced by cells heated to lethality above 54 degrees C and immediate medium exchange did not suppress the effect. Therefore, the thermal bystander effect appears to be an active process in which viable, heat-injured cells induce a signal cascade and/or mediator that damages or kills surrounding bystander cells. The ATBE may have clinical relevance for acute burn trauma, hyperthermic treatments, and distant tissue damage after localized heat stress.