Non-targeted Effects Are Involved In Low Dose ?-radiation-caused Wound Healing Delay

Purpose:Poorly penetrating alpha particles from natural sources do not cause perceptible skin injury unless the dose reaches several hundred Greys,but whether a-irradiation does not affect the skin at all is rarely studied.Previous study demonstrated that WS1 cell co-culturing with irradiated HaCaT suffered decay of migration.A hypothesis was proposed that weather radiation-induced bystander effects(RIBEs)would decay the wound healing in vivo.Therefore,we investigated the effects of ?-irradiation on skin wound healing and explored the role of RIBEs in the effects.Methods:BABL/c mice were irradiated with an alpha particle sources 241Am.Moreover,irradiation combined surgery wound model were created and the healing process was monitored.HE staining was used to evaluate the skin morphology and the thickness of the epidermis,the size of wound area was measured by using vernier calipers.Two weeks after radiation,skin samples were obtained for immunohistochemistry and immunoblot to analyze angiogenesis in re-epithelialization region.Then detect the expression of TGF-?1 and PGE2 in irradiation filed.In addition,we investigated if administration of a COX-2 inhibitor parecoxib in mice could stimulate the wound healing.Result:Delayed wound healing was induced by direct?-irradiation,and further pathological examination revealed an increase in the thickness of the wound epidermal layer in irradiated group.Immunoblot analysis and Immunohistochemistry both show that irradiated areas develop more new blood vessels.Delayed skin wound healing and increased angiogenesis were also observed in the co-culture group of the wound co-culture model after irradiation in vitro.?-irradiation treated increased the protein level of TGF-?1 and PGE2.Parecoxib administration increased the wound contraction and decreased angiogenesis of wound re-epithelialization region.Conclusion:It indicated that ?-irradiation did not cause visible skin damage symptoms but delayed wound healing,and RIBEs paly the important role in this phenomenon,which show that the biological effect of ?-irradiation is far more complicated than the previous concept.Farmore,more consideration should be taken in the radiation protection of application of ?-irradiation in clinical therapy and industry.Parecoxib administration improves the wound healing,it reveal that COX-2/PGE2 pro-inflammatory signaling plays an important role in RIBEs,which is significant in radiation protection.