INACTIVATION OF HYPOXIC CELLS BY CISPLATIN AND RADIATION AT CLINICALLY RELEVANT DOSES
INACTIVATION OF HYPOXIC CELLS BY CISPLATIN AND RADIATION AT CLINICALLY RELEVANT DOSES
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DOI：
10.2307/3577374
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发表时间：
1989-07-01
影响因子：
3.4
通讯作者：
SKOV, KA
中科院分区：
文献类型：
--
作者：
KORBELIK, M;SKOV, KA
我们研究了暴露于顺铂（顺二氨二氯铂（II））的影响，指数增长的V79细胞的反应，低（0-4戈伊）和高（高达30戈伊）剂量的X射线在缺氧和有氧条件下。通过克隆形成测定评估两个剂量区域中的存活率;通过细胞分析仪（B.帕尔西奇和B。贾吉，国际J。辐射。50，345-352（1986））。结果表明，顺铂，像它的异构体反式DDP，表现出更大的相互作用，低比高辐射剂量在缺氧细胞。甚至在低至1 μ mol dm-3的顺铂亚毒性暴露下也可以看到这种增加的相互作用。相比之下，在空气中照射的细胞在任一复合物的存在下，与高剂量的辐射所看到的相互作用是完全失去或大大减少在低辐射剂量区域。进一步的实验表明，低氧细胞与低剂量辐射的增强相互作用与顺铂在空气中或低氧中的预处理同样有效，即使细胞仅在辐射后暴露于顺铂。在非增殖平台期培养物的实验中，在低剂量区域观察到相同的增强相互作用。这些结果，例如5 μ mol dm-3顺铂在低剂量区和高剂量区的增强比分别为2.3和1.2，与硝基咪唑的结果形成对比，硝基咪唑在高剂量区是更好的敏化剂。
We have examined the effects of exposure to cisplatin (cis-diamminedichloroplatinum(II)) on the response of exponentially growing V79 cells to low (0-4 Gy) and high (up to 30 Gy) doses of X rays under hypoxic and aerobic conditions. Survival in both dose regions was assessed by clonogenic assays; the low-dose studies were facilitated by a Cell Analyser (B. Palcic and B. Jaggi, Int. J. Radiat. Biol. 50, 345-352 (1986)). The results show that cisplatin, like its isomer trans-DDP, exhibits greater interaction with low than with high radiation doses in hypoxic cells. This increased interaction could be seen even with subtoxic exposures to cisplatin as low as 1 .mu.mol dm-3. In contrast, with cells irradiated in air in the presence of either complex, the interaction seen with high doses of radiation is completely lost or greatly diminished in the low radiation dose region. Further experiments showed that enhanced interaction of hypoxic cells with low doses of radiation could be equally effective with cisplatin pretreatments in air or in hypoxia, even if the cells are exposed to cisplatin only after irradiation. In experiments with nonproliferating plateau-phase cultures, the same enhanced interaction was observed in the low-dose region. These results, for example enhancement ratios of 2.3 and 1.2 at low- and high-dose regions, respectively, for 5 .mu.mol dm-3 cisplatin, are contrasted with those for nitroimidazoles which are better sensitizers in the high-dose region.