Study Of C6 Glioma DNA-Targeting Radio-Therapy Byauger Electron Emitted From ～(125)IUDR On In Rats

Objective: To investigate the action and mechanism of Auger electron emitting from ¹²⁵IUDR on DNA-targeting radiotherapy of C6 glioma in rat based on establishment of a C6/SD glioma model.Methods: After establishing a C6/SD glioma model,by using flow cytometric analysis, immunohistochemistry and HE stain three methods, the proliferation kinetics in C6 glioma cell was measured. Then, based on the rat glioma model, a total of 50 male SD rat, weighing 250 to 300 gram, were randomingly divided into three groups: Experimental group(n=20), Control group (n=20) and Sham group (n=10). The animal of two former groups were separted into two subgroups: 5 day sacrificing group and survival analysis group. Experimental group were infused intracerebrally ¹²⁵IUDR per 8 hour during proliferation peak (0.2mCi/10μl/time), total dosage is 0.6mCi/rat. Control group were infused intracerebrally ¹²⁷IUDR per 8 hour(5.6uM/10ul/time), total dosage is 16.8 uM/rat. Sham group were infused with 10μl of 0.9% saline. Flow cytometric analysis and animal survival was followed overtime.Results: 1.After two weeks infused C6 glioma cell, the rat glioma model was established, tumor cell proliferated activity in HE stain. All indicators show tumor cellhad strong prolifercation activity. 2.Gross pathological examination demonstrated tumor weight and diameter in experimental group were lower than control group(P<0.05).3. HE stain show infraction area increased in control, but the increasing infraction area was larger in experimental group. In latter, apotosis cell increased significantly and proliferation index decreased markedly. 4.S phase fraction in experimental group decreased more than control group in flow cytometric analysis(P<0.001), cells in G2+M phase also decreased,and tumor cells were blocked in G0/G1 phase. Proliferation index in experimental group was lower than control^O.OOl), but apotosis index was higher(P<0.001).5.Two rats treated with )25IUDR survived over 50 days. The median survival of animals treated with 125IUDR (26 days) was markedly longer than that of control animals treated with 127IUDR (12 days) (P<0.05).Conclusions: l.Flow cytometric analysis,immunohistochemistry and HE stain had good correlation, and relected the different aspects in tumor cell proliferation. 2. 125IUDR can selectively kill S phase tumor cell, suppressed tumor cell proliferation, and extended the survival of tumor-bearing rats. 3. 125IUDR infused by tumor cell cycle made the drug concentration peak and tumor cell proliferation overlapped, and accomplished the accurate radiotherapy to tumor cell DNA-targeting. 4.125IUDR can damage cancerous cell by emittering Auger electrons to destroyed DNA, and induced the cancerous cell apotosis by ionization. The latter was a new findings in our study. 5. 125IUDR was taken up selectively by dividing cancerous cell, and had a widely value and prospect in clinical application.