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.
Purschke
Martin
M
Wellman Center for Photomedicine, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA. mpurschke@partners.org
Laubach
Hans-Joachim
HJ
Anderson
R Rox
RR
Manstein
Dieter
D
D017209:Apoptosis / Q000502:physiology*; D002056:Burns / Q000473:pathology*; D002450:Cell Communication / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D003470:Culture Media / Q000494:pharmacology; D004249:DNA Damage / Q000502:physiology*; D005334:Fever / Q000473:pathology; D005347:Fibroblasts / Q000473:pathology*; D018869:Heat-Shock Response / Q000502:physiology; D006358:Hot Temperature / Q000009:adverse effects*; D006801:Humans; D015162:Micronucleus Tests; D012867:Skin / Q000473:pathology
D003470:Culture Media