Biological Markers as Predictors of Radiosensitivity in Syngeneic Murine Tumors

Chang, Sei Kyung; Seong, Jinsil; Kim, Sung Hee; Shin, Hyun Soo

Abstract

PURPOSE: We investigated whether a relationship exists between tumor control dose 50 (TCD50) 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 TCD50, 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 8~12 weeks old when used for the experiments. The tumors, growing in the right hind legs of mice, were analyzed for TCD50, 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 performed whether the level of RIA were correlated with TCD50 or TGD, and the constitutive expression levels of genetic products regulating RIA were correlated with TCD50, 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 TCD50 (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 p34 showed a significant correlation either with TCD50 (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.