Radiation-induced DNA damage in tumors and normal tissues. I. Feasibility of estimating the hypoxic fraction.
Radiation-induced DNA damage in tumors and normal tissues. I. Feasibility of estimating the hypoxic fraction.
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DOI：
10.2307/3578643
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发表时间：
1993-10
影响因子：
3.4
通讯作者：
H. Zhang;K. Wheeler
中科院分区：
文献类型：
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作者：
H. Zhang;K. Wheeler
众所周知，电离辐射引起的DNA损伤的类型和数量取决于DNA周围的氧浓度。例如，在受辐射的哺乳动物细胞中，当细胞外氧浓度降低到1%以下时，DNA链断裂效率降低和DNA-蛋白质交联（DPC）的诱导都发生。在这里报道的研究中，通过测量单链断裂因子、DNA-蛋白质交联因子和用约24 ml pH 12.3的四丙基氢氧化铵（在裂解溶液中不含蛋白酶K（PK））洗脱后聚碳酸酯过滤器上剩余的DNA量，研究了估计辐照肿瘤和正常组织的缺氧分数的可行性。在麻醉的呼吸空气的Fisher 344大鼠中，当在剂量<或= 15戈伊后大约一半的修复时间测定DNA时，在小脑神经元或皮下（sc）9 L肿瘤细胞中均未检测到辐射诱导的DPC。在麻醉大鼠处死后10 min内，小脑神经元和sc 9 L肿瘤中放射诱导的DNA链断裂效率下降最多，放射诱导的DPC形成最多。当将来自呼吸空气和死亡大鼠的经辐照的小脑神经元或sc 9 L肿瘤细胞混合以模拟0、10、25、50、75和100%的缺氧分数时，在裂解溶液中没有PK的情况下，在约24 ml洗脱后，仅保留在过滤器上的DNA的百分比是15和2戈伊剂量后的模拟缺氧分数的线性函数。在15戈伊时，组织培养中的9 L细胞、sc 9 L肿瘤细胞和小脑神经元的线性函数相同。此外，斜率，但不是截距，线性函数似乎是独立的剂量从2到15戈伊。因此，如果链断裂修复的剂量和量保持相对恒定，则线性函数似乎主要取决于辐射化学事件，而不是被照射细胞的生物学性质。此外，数据表明，在2戈伊的常规放射治疗剂量后，该测定可以测量<或= 10%的缺氧分数，只要有足够的材料可用于分析。（400字处截断摘要）
It is well known that the type and quantity of DNA damage produced by ionizing radiation depend on the oxygen concentration around the DNA. For example, in irradiated mammalian cells, both a decrease in the DNA strand break efficiency and the induction of DNA-protein crosslinks (DPCs) occur as the extracellular oxygen concentration is decreased below 1%. In the study reported here, the feasibility of estimating the hypoxic fraction of irradiated tumors and normal tissues was investigated by measuring the single-strand scission factor, the DNA-protein crosslink factor, and the amount of DNA remaining on polycarbonate filters after elution with approximately 24 ml of tetrapropylammonium hydroxide at pH 12.3 without proteinase K (PK) in the lysis solution. In anesthetized air-breathing Fisher 344 rats, no radiation-induced DPCs were detected in either cerebellar neurons or cells of subcutaneous (sc) 9L tumors when the DNA was assayed at approximately one half-time of repair after doses < or = 15 Gy. Within 10 min after anesthetized rats were killed, the maximum decrease in the radiation-induced strand break efficiency and the maximum formation of radiation-induced DPCs occurred in both cerebellar neurons and sc 9L tumors. When irradiated cerebellar neurons or sc 9L tumor cells from air-breathing and dead rats were mixed to simulate hypoxic fractions of 0, 10, 25, 50, 75, and 100%, only the percentage of the DNA retained on the filter after approximately 24 ml of elution without PK in the lysis solution was a linear function of the simulated hypoxic fraction after doses of both 15 and 2 Gy. At 15 Gy, the linear function was identical for 9L cells in tissue culture, sc 9L tumor cells, and cerebellar neurons. In addition, the slope, but not the intercept, of the linear function appeared to be independent of dose from 2 to 15 Gy. Consequently, if the dose and the amount of strand break repair are kept relatively constant, the linear function appears to depend primarily on radiation chemistry events, rather than the biological properties of the irradiated cells. Moreover, the data suggest that this assay can measure a hypoxic fraction of < or = 10% after a conventional radiotherapy dose of 2 Gy, provided sufficient material is available for analysis.(ABSTRACT TRUNCATED AT 400 WORDS)