The Radiosensitizing Effect Of 9401

Hypoxic Cell is one of the important reasons which make tumorradiation therapy unsuccessful. Searching for high effectiveness andlow toxicity tumor radiosensitizer is an urgent task. A new drug9401(Nicotinoyl-iminodiacetic acid) was designed and synthesized byInstitute of Radiation Medicine, Chinese Academy of Medical Sciencesrecently. The initial experiments had shown: the radiosensitizingeffect of 9401 is better than Nicotinamide, and its cytotoxicity tonormal cells is lower than Nicotinamide. In order to verify theradiosensitizing effect of 9401 and provide academic proof forclinical application, we study the cytotoxicity and radiosensitizingeffect of 9401 on Hela cells in vitro by clongenic assay; We studythe radiosensitizing effect of 9401 on mice with H₂₂ hepatoma; and wealso study the radiosensitization of 9401 on normal tissue such asthe epithelia cell from mice small intestinal crypts and mice skinsin hind legs.The Thesis contains three subjects:1 The cytotoxicity and radiosensitization of 9401 on Hela cellsin vitro.2 The radiosensitization of 9401 on mice H₂₂ hepatoma.3 The radiosensitization of 9401 on normal tissue.The followings are the primary results of the study:1 The cytotoxicity of 9401 was in a dose-dependent manner. The50% inhibition concentration of 9401 was 4.65mg/ml. With 3mg/ml 9401exposed to Hela cells, after 3,6,12 and 24 hours, the correspondingSER_D0 were 1.33, 1.5, 1.63 and 1.67; SER_Dq were 1.38, 1.89, 2.47 and 3.33;SER_SF2 were 1.32, 1.82, 2.41 and 3.02. So 9401 has the cytotoxicity radiosensitizing effect to Hela cells, and the radiosensitization isdependent on time.2 We investigate the radiosensitizing effect of 9401 on themice H₂₂ hepatoma at the doses of 1g/kg 9401. The dose of radiationis 0Gy, 10Gy, 15Gy and 20Gy. Experiment results show: Compared to theradiation alone group, the days of tumor growth delay increasedobviously in the radiation and drug group. The sensitizationenhancement ratio is 1.30, so 9401 has obvious effect to thesensibility of mice H₂₂ hepatoma. Furthermore, the average tumor volumein the drug alone group and the control group has no distinctdifference, this result also reveals 9401 has no obvious effect ofresisting tumor in mice.3 The study of the radiosensitization of 9401 on the epitheliaof mice small intestinal crypts reveals: In the circumstances ofdifferent doses, it all showed there is no obvious difference inmacrography between the radiation alone group and the radiation anddrug group. It also did not show obvious difference (P＞0.05) afterstatistic adjustment. The sensitization enhancement ratio of 9401 is1.01. The study of the radiosensitization of 9401 on the mice skinsalso reveals: there is no obvious difference between the radiationalone group and the radiation and drug group, the sensitizationenhancement ratio of 9401 is 1.004. So 9401 has no obviousradiosensitizing effect on normal tissue.Inaword, 9401 has a good radiosensitizing effect on tumor tissue,but has no obvious effect on normal tissue. So 9401 is higheffectiveness and low toxicity, and hoping for clinic application.