Basic Studies on Physiological Factors in Radiocurability

辐射能量直接到达照射区域内的组织细胞，药物的传递依赖于血液循环，但即使吸收相同剂量的辐射，组织的反应也取决于其固有的辐射敏感性和生理因素，如氧分压。氧分压反过来又取决于通过血液供应的氧气和反映组织代谢活动的氧气消耗。在肿瘤的放射治疗中，关键是在不对正常组织造成严重损害的情况下有效地杀死肿瘤细胞。利用肿瘤组织和正常组织之间的生物/生理差异，通过分次照射可以获得不同的照射效果。本项目的目的是1)分析正常组织和肿瘤组织中的氧分压、能量水平和血流量，2)阐明照射后这两种组织之间这些参数的差异变化，并通过以上结果建立适用于人类受试者的预测分析系统。本项目的材料是小鼠纤维肉瘤NFSA2ALM1和鳞状细胞癌NRS1移植于C3H/He小鼠腿部。氧分压、能量水平(由^&lt；31&GT；P-MRS)、正常组织和肿瘤组织的血流量、肿瘤生长情况进行分析，收集基础数据。此外，还获得了一些关于辐照后氧分压和能级变化的信息。已经开始分析辐射后的“复氧”过程，并将结果与以前基于克隆形成试验的信息进行比较。然而，需要进一步调查才能得出最终结论。

Radiation energy directly reaches tissue cells within irradiated area, while drug delivery depends on blood circulation.Even the same dose is absorbed, however, the response of the tissues depends on their intrinsic radiosensitivity and physiological factors such as oxygen tension. Oxygen tension, in turn, depends on the oxygen supply through blood flow and the oxygen consumption reflecting the metabolic activity of the tissue.In radiation therapy of tumors what is essential is to kill tumor cells effectively without severe damage on normal tissues involved. The differential outcome of irradiation could be attained by fractionated irradiation utilizing biological/physiological difference between tumor tissues and normal ones.The aim of the present project has been 1) to analyze oxygen tension, energy level, and blood flow in normal and tumor tissues, 2) to clarify the differential changes in these parameters between the two kinds of tissues after irradiation, and, through the results obtained above, 3) to establish a predictive assay system which would be applicable to human subjects.The materials in the project were mouse fibrosarcoma NFSA2ALM1 and squamous cell carcinoma NRS1 transplanted in the legs of C3H/He mice.Oxygen tension, energy level (revealed by ^<31>P-MRS), blood flow in normal and tumor tissues, and growth of tumors have been analyzed and basic data were collected. Furthermore, some information on changes in oxygen tension and energy level after irradiation was also obtained. The analysis of the process of "reoxygenation" after irradiation and the comparison of the results to the previous information based on clonogenic assay has been initiated. Further investigation should, however, be needed to obtain a final conclusion.