Brown J M, Lemmon M J
Department of Radiation Oncology, Stanford University School of Medicine, CA 94305.
Int J Radiat Oncol Biol Phys. 1991 Mar;20(3):457-61. doi: 10.1016/0360-3016(91)90057-b.
The present study describes a new way in which tumors may be made more sensitive to fractionated irradiation without affecting the sensitivity of surrounding normal tissues. It involves exploiting the cycling or intermittent hypoxia that occurs in at least some solid tumors, but not in normal tissues, using a new drug SR 4233, a benzotriazine di-N-oxide, which is rapidly metabolized in hypoxic cells to a product that kills these cells. Using this approach with a rodent tumor in a fractionated x-ray treatment regimen similar to that used in human radiotherapy, the addition of SR 4233 produced a large enhancement of the radiation response of the tumor with no change in the sensitivity of normal mouse skin. Under identical circumstances, there was no effect of the hypoxic cell radiosensitizer SR 2508, showing that SR 4233 with intermittent hypoxia was superior to a protocol which sensitized the hypoxic cells to doses of 2.5 Gy per fraction.
本研究描述了一种新方法，可使肿瘤对分次照射更敏感，同时不影响周围正常组织的敏感性。该方法利用了至少某些实体瘤中存在但正常组织中不存在的循环性或间歇性缺氧，使用一种新药SR 4233，即苯并三嗪二-N-氧化物，它在缺氧细胞中迅速代谢为一种可杀死这些细胞的产物。在与人类放射治疗中使用的类似的分次X射线治疗方案中，将SR 4233用于啮齿动物肿瘤，结果显示添加SR 4233可显著增强肿瘤的放射反应，而正常小鼠皮肤的敏感性没有变化。在相同情况下，缺氧细胞放射增敏剂SR 2508没有效果，这表明伴有间歇性缺氧的SR 4233优于将缺氧细胞对每分次2.5 Gy剂量增敏的方案。
