Basic Studies on Physiological Factors in Radiocurability

辐射能直接到达被照射区域内的组织细胞，而药物的输送则依赖于血液循环。然而，即使吸收了相同的剂量，组织的反应也取决于其固有的放射敏感性和氧张力等生理因素。反过来，氧张力取决于通过血液流动的氧气供应和反映组织代谢活动的氧气消耗。在肿瘤的放射治疗中，关键是要有效地杀死肿瘤细胞，而不严重损害正常组织。利用肿瘤组织与正常组织的生物/生理差异，通过分级照射可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的氧张力、能量水平和血流，2)阐明两种组织在辐照后这些参数的差异变化，并通过上述结果，3)建立适用于人类受试者的预测分析系统。本项目材料为移植于C3H/He小鼠腿部的小鼠纤维肉瘤NFSA2ALM1和鳞状细胞癌NRS1。分析正常组织和肿瘤组织的氧张力、能量水平（由^<31>P-MRS显示）、血流以及肿瘤的生长情况，并收集基本数据。此外，还获得了辐照后氧张力和能级变化的一些信息。对辐照后的“再氧化”过程进行了分析，并与以往的克隆测定结果进行了比较。但是，需要进一步调查才能得出最后结论。

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.