Induction of tumour hypoxia post-irradiation: a method for increasing the sensitizing efficiency of misonidazole and RSU 1069 in vivo.
Induction of tumour hypoxia post-irradiation: a method for increasing the sensitizing efficiency of misonidazole and RSU 1069 in vivo.
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照射后诱导肿瘤缺氧：一种提高米索硝唑和 RSU 1069 体内致敏效率的方法。
DOI：
10.1080/09553008914550451
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发表时间：
1989
影响因子：
2.6
通讯作者：
Howells,N
中科院分区：
文献类型：
--
作者：
Stratford,IJ;Adams,GE;Godden,J;Howells,N
众所周知，肼屈嗪可以减少实验性小鼠肿瘤的血流量。其结果是，在 KHT 肉瘤中，导致接近 100% 的放射生物学缺氧，这种缺氧在静脉注射后持续近 2 小时。给小鼠注射5mg/kg肼屈嗪。这种现象可用于提高硝基杂环放射增敏剂、米索硝唑和RSU 1069的表观增敏效率，并使用治疗方案进行了证明：增敏剂→60分钟→X射线→1分钟→肼屈嗪。这种策略将首先利用硝基咪唑的放射增敏特性，然后在照射后，肼苯哒嗪应允许对已知与米索硝唑和RSU 1069一起发生的缺氧细胞表现出不同的毒性。米索硝唑在100 mg/kg时的增强比（ER）为1·3，在1000 mg/kg时升至2·0。当照射后给予肼屈嗪时，1000 mg/kg 时没有观察到额外的细胞死亡。相反，在较低剂量的米索硝唑下，肼屈嗪会诱导细胞杀伤作用显着增加，因此用 100 mg/kg 获得的 ER 与单独使用放射线时用 1000 mg/kg 米索硝唑获得的 ER 相同。类似地，20 mg/kg RSU 1069 辐射后加肼屈嗪相当于 80 mg/kg RSU 1069 不加肼屈嗪的放射增敏作用。此外，通常不产生放射增敏作用的 RSU 1069 剂量（5 或 10 mg/kg）与肼屈嗪联合使用时，会显着增加细胞杀伤力。
It is known that hydralazine can decrease blood flow to experimental murine tumours. A consequence of this, in the KHT sarcoma, is the induction of close to 100 per cent radiobiological hypoxia, which lasts for nearly 2 h following i.v. injection of 5 mg/kg hydralazine to the mouse. This phenomenon is exploitable in order to increase the apparent sensitizing efficiency of the nitroheterocyclic radiosensitizers, misonidazole and RSU 1069, and is demonstrated using the treatment schedule: sensitizer→60 min→X-rays→1 min→hydralazine. Such a strategy will first take advantage of the radiosensitizing properties of the nitroimidazole, then after irradiation the hydralazine should allow expression of the differential toxicity towards hypoxic cells known to occur with misonidazole and RSU 1069.Misonidazole gives an enhancement ratio (ER) of 1·3 at 100 mg/kg, rising to 2·0 at 1000 mg/kg. Where hydralazine is given after irradiation,noadditional cell kill is observed with 1000 mg/kg. In contrast, at lower doses of misonidazole, hydralazine induces a substantial increase in cell killing such that the ER obtained with 100 mg/kg is the same as that achieved with 1000 mg/kg misonidazole when used alone with radiation. Similarly, 20 mg/kg RSU 1069 with radiation followed by hydralazine is equivalent to the radiosensitizing effect of 80 mg/kg RSU 1069 without hydralazine. In addition, doses of RSU 1069 that normally give no radiosensitization (5 or 10 mg/kg) produce substantial increases in cell killing when combined with hydralazine.