MUTATION AND INACTIVATION OF CULTURED MAMMALIAN-CELLS EXPOSED TO BEAMS OF ACCELERATED HEAVY-IONS .4. BIOPHYSICAL INTERPRETATION
MUTATION AND INACTIVATION OF CULTURED MAMMALIAN-CELLS EXPOSED TO BEAMS OF ACCELERATED HEAVY-IONS .4. BIOPHYSICAL INTERPRETATION
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DOI：
10.1080/09553008014550201
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发表时间：
1980-01-01
影响因子：
2.6
通讯作者：
COX, R
中科院分区：
文献类型：
--
作者：
GOODHEAD, DT;MUNSON, RJ;COX, R
对使用20-470 keV/μm加速重离子诱导培养的V79中国仓鼠细胞和HF19人二倍体成纤维细胞失活和突变（6-硫鸟嘌呤抗性）的实验结果进行了生物物理分析。在从观察到的放射敏感性推断诱导致死和诱变损伤的数量之前，必须明确考虑初级离子的离散性质。将测量的不同 LET（线性能量转移）辐射产生的损伤数量与各种辐射作用模型预测的相对数量进行比较。这些观察结果可以用以下假设来解释：每个致命损伤是由约 3 nm 距离内的小能量沉积（少量电离）产生的。似乎涉及两种不同的病变：一种需要.gtorsim。 100 eV，并且以低 LET 辐射为主，而另一个则需要 .gtorsim。 300 eV，在高 LET 下占主导地位。类似的结论可能适用于诱变损伤，只是在高 LET 下占主导地位的机制需要明显超过 300 eV。对假设和这些数值的更精确评估必须等待纳米尺度辐射的详细轨道结构计算。调用亚致死损伤累积或微米级距离内亚损伤之间相互作用的替代模型无法对观察结果提供一致的解释。经常观察到的低 LET 剂量反应的曲率并不是由于亚病变之间的相互作用，而是由于一些其他机制，例如剂量依赖性修复过程。低速、高 LET 离子在穿过上述哺乳动物细胞的细胞核时平均产生明显 < 1 个致命损伤； 90 keV/μm He 离子穿过厚度约为 7μm 的细胞核，产生约 0.03-0.06 个致命损伤/μm 的轨迹。还对核区域的大小进行了一些估计，该核区域对诱导 6-硫鸟嘌呤抗性突变敏感；这个区域延伸到结构基因本身的DNA之外。
A biophysical analysis was made of the results of experiments which used accelerated heavy ions of 20-470 keV/.mu.m to induce inactivation and mutation (resistance to 6-thioguanine) in cultured V79 Chinese hamster cells and HF19 human diploid fibroblasts. The discrete nature of the primary ions must be explicitly taken into account before the numbers of induced lethal and mutagenic lesions can be deduced from the observed radiosensitivities. The measured numbers of lesions produced by the radiations of different LET [linear energy transfer] are compared with the relative numbers predicted by various models of radiation action. The observations can be explained on the hypothesis that each lethal lesion is produced by a deposition of small energy (small number of ionizations) in a distance of about 3 nm. Two different lesions appear to be involved: one which requires .gtorsim. 100 eV and is dominant with low-LET radiations, and another which requires .gtorsim. 300 eV and is dominant at high-LET. Similar conclusions may apply to mutagenic lesions except that the mechanism which dominates at high-LET requires significantly more than 300 eV. More precise assessments of the hypothesis and these numerical values must await detailed track structure calculations of the radiation on the nanometer scale. Alternative models which invoke accumulation of sublethal damage or interaction between sublesions over distances of the order of microns do not provide a consistent explanation of the observations. The frequently observed curvature of low-LET dose-responses is not due to interaction between sublesions but rather to some other mechanism such as a dose-dependent repair process. Low velocity, high-LET ions produce an average of appreciably < 1 lethal lesion in traversing the nucleus of the above mammalian cells; 90 keV/.mu.m He ions produce about 0.03-0.06 lethal lesions/.mu.m of track through the nucleus of the cells of thickness about 7 .mu.m. Some estimates are also made of the size of the nuclear region which is sensitive to the induction of mutation to 6-thioguanine-resistance; this region extends beyond the DNA of the structural gene itself.