Radiation Oncology Journal

The Korean Society for Radiation Oncology (대한방사선종양학회)
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Effects of Recombinant Human Epidermal Growth Factor (rhEGF) on Experimental Radiation-Induced Oral Mucositis in Rats

Rat의 방사선 조사성 구내염에 대한 Recombinant Human Epidermal Growth Factor (rhEGF)의 효과

  • Jung Kwon-Il (Departments of Toxicology and Pharmacology, Institute of Bioscience and Biotechnology, Daewoong Pharmaceutical Co., LTD.) ;
  • Kim Sun-Hee (Departments of Protein Drug Development, Institute of Bioscience and Biotechnology, Daewoong Pharmaceutical Co., LTD.) ;
  • Moon Soo-Young (Departments of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Kim Yeon-Wha (Departmants of Plastic Surgery Oncology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Hong Joon-Pio (Departmants of Plastic Surgery Oncology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Kim Hyun-Sook (Department of Radiology, Gyeongsang National University College of Medicine) ;
  • Lee Sang-Wook (Departments of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center)
  • 정권일 (대웅제약 생명공학연구소 약리독성팀) ;
  • 김선희 (대웅제약 생명공학연구소 단백질의약팀) ;
  • 문수영 (울산대학교 의과대학 서울아산병원 방사선종양학과) ;
  • 김연화 (울산대학교 의과대학 서울아산병원 성형외과) ;
  • 홍준표 (울산대학교 의과대학 서울아산병원 성형외과) ;
  • 김현숙 (경상대학교 의과대학 방사선과학교실) ;
  • 이상욱 (울산대학교 의과대학 서울아산병원 방사선종양학과)
  • Published : 2006.03.01
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Abstract

Purpose: Oral mucositis is a common toxicity of radiation or chemotherapy, which is used a treatment for head and neck cancer. We investigated effects of recombinant human epidermal growth factor (rhEGF) on radiation-induced oral mucositis in rat model. Materials and Methods: Spraque-Dawley rats (7 per group) exposed to a single dose of 25 Gy (day 0) on their head, except for one group, were randomly divided into un-treated, vehicle-treated, and two rhEGF-treated groups. Rats were topically applied with rhEGF (15 or $30{\mu}g/oral$ cavity/day) or vehicle to their oral mucosa. Survival rate of rats, weight changes, and food intakes were examined from day 0 to 18 after radiation. Histology study was performed from oral mucosa of rats at day 7 and 18 after radiation. Results: rhEGF-treated groups (15 or $30{\mu}g/oral$) showed all survival rate 33%, whereas un-treated and vehicle-treated groups showed all survival rate 0% at the end of experiment. rhEGF-treated groups statistically had less weight loss compared to vehicle-treated group from day 2 to 7 after radiation. Food intake of rats with rhEGF treatment turned to increase at day 14 after radiation. At 7 day after radiation, un-treated and vehicle-treated groups showed severe pseudomembraneous or ulcerative oral mucositis. On the other hand, rhEGF-treated groups had no more than cellular swelling and degeneration of epidermal cells in oral mucosa of rats. Conclusion: These results suggest that rhEGF has significantly positive effects on radiation-induced oral mucositis in rats. rhEGF display a therapeutic potential on a clinical level.

목적 : 구내염은 두경부종양이 있는 암환자에게 방사선 및 항암제 치료 시술 시 매우 흔하게 발생하는 합병증이다. 본 연구는 Rat 의 방사선성 구내염 모델에서 recombinant human epidermal growth factor (rhEGF)의 효과를 평가하고자 하였다. 대상 및 방법: 25 Gy의 방사선량으로 두부에 단회 조사한 Rat를 무작위로 7마리씩 무처치군, 부형제 처치군, rhEGF 15 또는 $30{\mu}g/day$ 구강 내 처치군으로 나누었으며, 방사선을 조사하지 않은 7 마리의 Rat를 정상시험군으로 나누었다 rhEGF 시료 및 부형제는 1일 3회 Rat 의 구강점막에 매일 도포하였다. Rat의 생존율, 체중변화 및 사료섭취량을 18일 동안 관찰하였으며, 방사선 조사 후 7 일 및 18 일째에 Rat의 구강점막을 조직학적으로 평가하였다. 결과 : 실험종료 시점에서 rhEGF 15 또는 $30{\mu}g/day$ 구강 내 처치군이 모두 33%의 생존율을 보인 것에 비하여, 무처치군 및 부형제 처치군은 모두 0%의 생존율을 보였다. 체중변화에서도 rhEGF 처치군은 방사선 조사 후 2일부터 7일까지 부형제 처치군에 비하여 Rat 의 평균체중이 통계적으로 더욱 무거웠다 사료섭취율은 모든 시험군에서 방사선 조사 후 4 일까지 감소하는 양상을 보이다가, rhEGF 15 또는 $30{\mu}g/day$ 구강 내 처치군에서 14일째에 뚜렷한 사료섭취율의 증가가 관찰되었다. 방사선 조사 후 7 일째의 조직학적 분석 결과, rhEGF 15 또는 $30{\mu}g/day$ 구강 내 처치군의 Rat 에서는 점막 표피층의 각질세포의 종창 및 변성만이 관찰되었던 것에 비하여, 무처치군 및 부형제 처치군에서는 심한 위막성 또는 궤양성 구내염이 관찰되었다. 결론; rhEGF (15 또는 $30{\mu}g/day$ 구강 내 처치군) 처치에서 방사선 조사로 유발시킨 Rat의 구내염 모델에서 유의성 있는 치유 효과를 확인하였으며, 본 시험결과로 rhEGF가 방사선에 의해 유발된 구내염을 치료할 수 있는 임상 제제로써의 가능성을 볼 수 있었다.

Keywords

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