Radiation Oncology Journal

The Korean Society for Radiation Oncology (대한방사선종양학회)
권호 표지

Biological Markers as Predictors of Radiosensitivity in Syngeneic Murine Tumors

동계 마우스 종양의 방사선 감수성 예측인자로서의 생물학적 표지자

  • Chang Sei-Kyung (Department of Radiation Oncology, Pochon CHA University, Bundang CHA General Hospital) ;
  • Kim Sung-Hee (Department of Radiation Oncology, Yonsei University College of Medicine) ;
  • Shin Hyun-Soo (Department of Radiation Oncology, Pochon CHA University, Bundang CHA General Hospital) ;
  • Seong Jin-Sil (Department of Radiation Oncology, Yonsei University College of Medicine)
  • 장세경 (포천중문의과대학교 분당차병원 방사선종양학과) ;
  • 김성희 (연세대학교 의과대학 방사선종양학교실) ;
  • 신현수 (포천중문의과대학교 분당차병원 방사선종양학과) ;
  • 성진실 (연세대학교 의과대학 방사선종양학교실)
  • Published : 2006.06.01
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Abstract

Purpose: We investigated whether a relationship exists between tumor control dose 50 ($TCD_{50}$) or tumor growth delay (TGD) and radiation induced apoptosis (RIA) in syngeneic murine tumors. Also we investigated the biological markers that can predict radiosensitivity in murine tumor system through analysis of relationship between $TCD_{50}$, TGD, RIA and constitutive expression levels of the genetic products regulating RIA. Materials and Methods: Syngeneic murine tumors such as ovarian adenocarcinoma, mammary carcinoma, squamous cell carcinoma, fibrosarcoma, hepatocarcinoma were used In this study. C3H/HeJ mice were bred and maintained in our specific pathogen free mouse colony and were $8{\sim}12$ weeks old when used for the experiments. The tumors, growing in the right hind legs of mice, were analyzed for $TCD_{50}$, TGD, and RIA at 8 mm in diameter. The tumors were also analyzed for the constitutive expression levels of $p53,\;p21^{WAF1/CIP1},\;BAX,\;Bcl-2,\;Bcl-X_L,\;Bcl-X_S$, and p34. Correlation analysis was peformed whether the level of RIA were correlated with $TCD_{50}$ or TGD, and the constitutive expression levels of genetic products regulating RIA were correlated with $TCD_{50}$, TGD, RIA. Results: The level of RIA showed a significant positive correlation (R=0.922, p=0.026) with TGD, and showed a trend to correlation (R=-0.848), marginally significant correlation with $TCD_{50}$ (p=0.070). It indicates that tumors that respond to radiation with high percentage of apoptosis were more radiosensitive. The constitutive expression levels of $p21^{WAF1/CIP1}$ and 34 showed a significant correlation either with $TCD_{50}$ (R=0.893, p=0.041 and R=0.904, p=0.035) or with TGD (R=-0.922, p=0.026 and R=-0.890 p=0.043). The tumors with high constitutive expression levels of $p21^{WAF1/CIP1}$ or p34 were less radiosensitive than those with low expression. Conclusion: Radiosensitivity may be predicted with the level of RIA in murine tumors. The constitutive expression levels of $p21^{WAF1/CIP1}$ or p34 can be used as biological markers which predict the radiosensitivity.

목적: 방사선 감수성이 다양한 동계(syngeneic) 마우스 종양들을 대상으로 50% 종양억제선량과 종양성장지연 등 방사선 감수성을 대변하는 지표와 방사선에 의해 유도되는 아포토시스 간에 상관관계가 있는지 여부를 알아보고자 하였다. 또한 아포토시스와 관련된 여러 유전물질의 기본(constitutive) 발현수준을 측정한 후 이들 상호 간의 상관관계를 분석하여 방사선 감수성을 예측할 수 있는 생물학적 표지자를 알아보고자 하였다. 대상 및 방법: 동계 마우스 종양으로는 난소암 OCa-1, 유방암 MCa-K, 편평상피세포암 SCC-VII, 섬유육종 FSa-II, 간암 HCa-1을 사용하였고 이들은 PCR-SSCP 검사상 p53이 모두 자연형인 종양들이었고 주령 $8{\sim}10$ 주인 C3H/HeJ 웅성 마우스를 사용하였다. 50% 종양억제선량과 종양성장지연 및 방사선에 의해 유도되는 아포토시스를 측정하여 이들과 방사선에 의해 유도되는 아포토시스간의 상관관계를 분석하여 방사선에 의해 유도되는 아포토시스로 방사선 감수성을 예측할 수 있는지 여부를 알아보고, 또한 아포토시스와 관련된 유전물질 $053,\;p21^{WAF1/CIP1},\;BAX,\;Bcl-2,\;Bcl-x_L,\;Bcl-X_s,\;p34$ 등의 기본 발현양상 및 발현수준을 Western blot과 농도계측기로 측정한 후 이들 상호 간의 상관관계를 분석하였다. 결과: 방사선에 의해 유도된 아포토시스의 정도와 종양성장지연과의 사이에는 통계적으로 유의한 상관관계가 존재하였다(R=0.922, p=0.026). 50% 종양억제선량과의 사이에는 통계적 유의성은 변연수준이었으나(p=0.070) 상관관계의 경향을 보였다(R=-0.848). $p21^{WAF1/CIP1}$과 p34의 기본 발현수준과 50% 종양억제선량(R=0.893, p=0.041와 R=0.904, p=0.035) 및 종양성장지연(R=-0.922, p=0.026와 R=-0.890, p=0.043) 사이에는 통계적으로 유의한 상관관계가 존재하였다. 즉, $p21^{WAF1/CIP1}$과 p34의 기본 발현수준이 낮은 경우에 방사선 감수성이 높고, 기본 발현수준이 높은 경우에는 방사선 감수성이 낮은 상관관계가 존재함을 알 수 있었다. 결론: 방사선에 의해 유도된 아포토시스의 정도로 종양의 방사선 감수성을 예측하여 볼 수 있을 것으로 생각하며, 종양의 방사선 감수성을 예측할 수 있는 생물학적 표지자로 $p21^{WAF1/CIP1}$와 p34의 기본 발현수준이 이용될 수 있을 것으로 생각한다.

Keywords

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