The Experimental Studies On Radiobiological Effects After Fractionated Irradiation In The Glioma

Objective: To evaluate and measure the radiobiological factors and tumor response in cell line and xenograft of human glioma after single and fractionated radiation, in order to provide a conceptive basis in cellular and tumor response of the glioma for clinic radiotherapy.Materials and Methods: The xenograft of the human glioma established by our lab and animal experimental lab was used to evaluate the dose——effect relationship after single and fractionated irradiation with various radiation schedules. The exponential growing phase BT325 cell line (from the Beijing neural surgical research institute) was used to determine the cell doubling time, the kinetic parameters in cell cycle and the radiobiological parameters. The volume doubling time was determined by the xenograft of human glioma growth curve.Results: The results in our experiments showed that (1) in the fractionated radiation schedules of the 200cGy×5/w or 300cGy×3/w, no significant tumor regression was observed in the xenograft of human glioma. It is suggested that the two schedules are not good for solid tumor control and a improving schedule would be needed. In the 400cGy×3/w schedule, the tumor regression was better than others, but all of the treatment schedules could not cure the tumors, especially in single large irradiation with poor tumor control, it means that there are stem cells remained and the further improving schedule should be needed. (2) The cell doubling time of the BT325 cell line was 30.16 hours and the volume doubling time of the xenograft of the human glioma was 43 days according to the cell growth curve and the tumor growth curve, respectively. (3) The radiation surviving curve's parameters wereα=0.036,β=0.057 (fitted by LQ model) and D₀=1.394Gy, Dq=2.127Gyand SF₂=0.714Gy (fitted by the single-hit multi-target model), respectively. (4) The parameters in cell cycle kinetics exposed to different radiation dose tend to experience a cell reduce in the G1 and a block in the G2/M, this phenomenon was more apparently with radiation dose increased.Conclusions: Results in our experiments (according to the in vitro and in vivo experiments) suggested that the glioma was a resistant tumor to radiation, not only in xenograft but also in vitro cells. Elevating the fraction dose might improve the tumor regression rate, but how to increase tumor control would need further approaches. Further more, the cell doubling time in BT325 cell line and the tumor volume doubling time xenografts of the human glioma were longer than most of the tumor cell lines, also suggesting the glioma with low radiosensitivity. The further mechanisms need to make further studies.