Brown J M, Lemmon M J
Department of Radiation Oncology, Stanford University School of Medicine, CA 94305.
Radiother Oncol. 1991;20 Suppl 1:151-6. doi: 10.1016/0167-8140(91)90203-s.
The benzotriazine SR 4233, in addition to preferential killing of hypoxic cells both in vitro and in vivo, also radiosensitizes aerobic cells in vitro if the cells are exposed to the drug under hypoxic conditions, either before or after irradiation. We have attempted to exploit this aerobic radiosensitization in vivo, by giving SR 4233 with the hypoxia inducing agent, hydralazine, after each radiation dose in a 8 x 2.5 Gy fractionated regime. The results show greater than additive cytotoxicity using both cell survival and regrowth delay as the endpoints of radiation response, but no radiosensitization in parallel groups treated with the hypoxic cell radiosensitizer SR 2508. The data are, therefore, consistent with radiosensitization of the tumor aerobic cells by the SR 4233 treatments. Significantly, the effect occurred with equal magnitude with or without hydralazine. Further, there was no radiosensitization to radiation induced leg contraction in the thighs of mice, a late responding normal tissue endpoint. The results, therefore, demonstrate a selective radiosensitization of tumors to a multifraction regime and suggest that SR 4233, or a close analog, may be useful in radiation therapy.
苯并三嗪SR 4233除了在体外和体内对缺氧细胞具有优先杀伤作用外，如果细胞在缺氧条件下，于照射前或照射后接触该药物，它还能在体外使需氧细胞产生放射增敏作用。我们试图通过在8×2.5 Gy分割照射方案的每次照射剂量后，将SR 4233与缺氧诱导剂肼苯哒嗪联合使用，来利用这种体内需氧放射增敏作用。结果显示，以细胞存活和再增殖延迟作为放射反应的终点指标时，联合用药具有大于相加的细胞毒性，但在用缺氧细胞放射增敏剂SR 2508处理的平行组中未观察到放射增敏作用。因此，这些数据与SR 4233处理使肿瘤需氧细胞产生放射增敏作用一致。值得注意的是，无论有无肼苯哒嗪，该效应的程度相同。此外，在小鼠大腿部对辐射诱导的腿部收缩这一晚期反应正常组织终点指标上，未观察到放射增敏作用。因此，这些结果证明了肿瘤对多分次照射方案具有选择性放射增敏作用，并表明SR 4233或其类似物可能在放射治疗中有用。
