DOI QR코드

DOI QR Code

Gamma-ray-induced skin injury in the mini-pig: Effects of irradiation exposure on cyclooxygenase-2 expression in the skin

감마선조사에 의한 돼지 피부장애에 cyclooxygenase-2의 발현변화

  • Received : 2015.01.16
  • Accepted : 2015.03.19
  • Published : 2015.03.31

Abstract

The basic concepts of radiation-induced skin damage have been established, the biological mechanism has not been studied. In this study, we have examined the effects of gamma rays on skin injury and cyclooxygenase(COX)-2 expression. Gamma irradiation induced clinicopathological changes in a dose- and time-dependent manner in mini-pig skin. The histological changes were consistent with the changes in gross appearance at 12 weeks after irradiation. After three days' irradiation, apoptotic cells in the basal layer were found more frequently in irradiated skin than in normal skin, with the magnitude of the effect being dose-dependent. The thickness of the epidermis transiently increased 3 days after irradiation, and then gradually decreased, although changes in the epithelial thickness of the irradiated field were not observed with irradiation doses over 50 Gy. In the epithelium, there was an initial degenerative phase, during which the rate of basal cell depletion was dependent on the radiation dose (20-70 Gy). One week after irradiation, COX-2 expression was mostly limited to the basal cell layer and was scattered across these cells. High COX-2 expression was detected throughout the full depth of the skin after irradiation. The COX-2 protein is upregulated after irradiation in mini-pig skin. These histological changes associated with radiation exposure dose cause the increased COX-2 expression in a dose-dependent fashion.

방사선 노출에 따른 피부손상의 기본이론들은 정립되어 있지만, 정확한 기전에 관해서는 알려지지 않은 실정이다. 본 연구에서는 감마선 조사 후 용량 및 시간에 따라 돼지 피부의 장애를 육안 및 조직학적인 변화를 통해 평가하고 cyclooxygenase(COX)-2 발현 정도를 비교하고자 하였다. 미니돼지의 등 쪽 피부에 20-70 Gy 감마선을 국소조사 후 12 주 동안 육안적인 변화를 관찰하고 생검을 통해 조직학적인 변화를 관찰하였다. 방사선 조사 후 피부의 기저세포층에서의 세포자멸사와 표피층의 두께 변화를 평가하였고 COX-2 발현 정도를 면역염색을 통하여 비교하였다. 방사선 조사 후 피부 장애는 용량이 증가할수록 피부손상이 더욱 심하였으며 초기에 발적 소견을 보이다가 50 Gy 이상 조사군에서는 미란과 궤양으로 이어졌다. 조직학적인 변화는 육안적인 소견과 일치하였다. 방사선 조사 후 3일부터 기저세포에서 세포자멸사가 관찰되었으며 기저세포수의 감소가 유발되었으며 이러한 변화는 용량이 증가할수록 더욱 증가하였다. 방사선 조사 후 표피층의 두께는 3일 무렵에 일시적으로 증가하다가 점차 감소하였으며 20, 30, 40 Gy 조사 군에서는 다시 회복되는 소견이 관찰되었으나 50, 70 Gy 조사 군에서는 다시 회복되지 못하고 표피창의 두께 소실을 보였다. 방사선 조사 후 피부에서의 COX-2 발현은 피부손상정도와 일치하게 관찰되었다. 방사선 조사 후 COX-2 발현은 방사선의 용량이 증가할수록 발현이 증가하였고 시간이 증가할수록 증가하였다. 이러한 조직학적인 변화와 함께 방사선 손상을 일으키는 신호전달에 관여하는 COX-2 발현이 방사선조사 용량에 비례하여 증가하며 이러한 단백질의 발현은 피부손상과 관련성이 높은 것으로 사료된다.

Keywords

References

  1. Hopewell JW. The skin: its structure and response to ionizing radiation. Int J Radiat Biol. 1990;57:751-73. https://doi.org/10.1080/09553009014550911
  2. Lee HJ, Kim SH. Relative biological effectiveness of fast neutrons for apoptosis in mouse hair follicles. J Vet Sci. 2007;8(4):335-40. https://doi.org/10.4142/jvs.2007.8.4.335
  3. Simon GA, Maibach HI. The pig as an experimental animal model of percutaneous permeation in man: qualitative and quantitative observations-an overview. Skin Pharmacol Appl Skin Physiol. 2000; 13(5):229-34. https://doi.org/10.1159/000029928
  4. Sullivan TP, Eaglstein WH, Davis SC, Mertz P. The pig as a model for human wound healing. Wound Repair Regen. 2001;9(2):66-76. https://doi.org/10.1046/j.1524-475x.2001.00066.x
  5. Ma ZF, Chai JK, Yang HM, Liu Q, Xu MH, Yin HN. Acellular porcine dermal matrix produced with different methods and an experimental study on its transplantation to skin wound. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2005;17(2):92-94.
  6. Archambeau JO, Pezner R, Wasserman T. Pathophysiology of irradiated skin and breast. Int J Radiat Oncol Biol Phys. 1995; 31:1171-85. https://doi.org/10.1016/0360-3016(94)00423-I
  7. Takeuchi K1, Tanaka A, Kato S, Amagase K, Satoh H. Roles of COX inhibition in pathogenesis of NSAID-induced small intestinal damage. Clin Chim Acta. 2010;411(7-8):459-66. https://doi.org/10.1016/j.cca.2009.12.026
  8. O'Neill GP, Ford-Hutchinson AW. Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues. FEBS Lett. 1993;330:156-60.
  9. Athar M, An KP, Morel KD, Kim AL, Aszterbaum M, Longley J, Epstein EH Jr, Bickers DR. Ultraviolet B(UVB)-induced cox-2 expression in murine skin: an immunohistochemical study. Biochem Bioph Res Co. 2001;280(4):1042-7. https://doi.org/10.1006/bbrc.2000.4201
  10. Williams CS, Mann M, DuBois RN. The role of cyclooxygenases in inflammation, cancer, and development. Oncogene. 1999; 18(55):7908-16. https://doi.org/10.1038/sj/onc/1203286
  11. Yeoh AS, Bowen JM, Gibson RJ, Keefe DM. Nuclear factor kappaB (NFkappaB) and cyclooxygenase-2 (Cox-2) expression in the irradiated colorectum is associated with subsequent histopathological changes. Int J Radiat Oncol Biol Phys. 2005;63(5):1295-303. https://doi.org/10.1016/j.ijrobp.2005.04.041
  12. Kim JS, Rhim KJ, Jang WS, Lee SJ, Son Y, Lee SS, Park S, Lim SM. $\beta$-Irradiation (166Ho patch)-induced skin injury in the mini pig: effects on $NF-{\kappa}B$ and COX-2 expression in the skin. J Vet Sci. 2015;16(1): 1-9. https://doi.org/10.4142/jvs.2015.16.1.1
  13. Randall K, Coggle JE. Long-term expression of transforming growth factor TGF beta 1 in mouse skin after localized beta-irradiation. Int J Radiat Biol. 1996;70(3):351-60. https://doi.org/10.1080/095530096145085
  14. Morris GM, Hopewell JW. Cell kinetic changes in the follicular epithelium of pig skin after irradiation with single and fractionated doses of X rays. Brit J Radiol 1989;62:41-7. https://doi.org/10.1259/0007-1285-62-733-41
  15. Liang L, Hu D, Liu W, Williams JP, Okunieff P, Ding I. Celecoxib reduces skin damage after radiation: selective reduction of chemokine and receptor mRNA expression in irradiated skin but not in irradiated mammary tumor. Am J Clin Oncol-Canc. 2003;26(4):S114-21.

Cited by

  1. Comparison of Skin Injury Induced by β- and γ-irradiation in the Minipig Model vol.42, pp.4, 2015, https://doi.org/10.14407/jrpr.2017.42.4.189