Thermal Injury Causes DNA Damage and Lethality in Unheated Surrounding Cells: Active Thermal Bystander Effect

Abstract

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.