Sachs R K, Chen A M, Simpson P J, Hlatky L R, Hahnfeldt P, Savage J R
Department of Mathematics, University of California, Berkeley 98220, USA.
Int J Radiat Biol. 1999 Jun;75(6):657-72. doi: 10.1080/095530099139999.
For high-LET radiations, and perhaps even for hard X-rays, DNA double-strand breaks (dsb) are clustered nonrandomly along chromosomes; disproportionately, many inter-dsb segments are less than a few Mbp (10(6) base pairs). The implications of such dsb clustering for chromosome aberrations are analysed.
Chromosome segments between different dsb within one dsb cluster are assumed too small to detect in the aberration assay. Enumeration or Monte-Carlo computer simulations are used to compute the relative frequencies of many observable aberration patterns: apparently simple or visibly complex. The theoretical predictions are compared with X-ray data for human fibroblasts, involving painted chromosomes 1, 2, 4, 5, 7 or 13.
Surprisingly, cryptic dsb multiplicity does not affect the frequency ratios predicted for aberration patterns by a random breakage-and-rejoining model. The model is generally consistent with current data on many different types of aberrations, whether or not dsb usually occur in cryptic clusters. For a Revell-type exchange model, however, the predictions do depend on clustering configurations; they gradually approach the predictions of the breakage-and-rejoining model as average cluster multiplicity increases. The model is consistent with the data, for example with the ratio of visibly complex to apparently simple aberrations, only if there is considerable dsb clustering even at low-LET, with approximately 1.5 or more reactive dsb per cluster on average.
对于高传能线密度辐射，甚至可能对于硬X射线，DNA双链断裂（dsb）沿染色体呈非随机聚集；许多双链断裂间片段短于几兆碱基对（10⁶个碱基对），比例失调。分析这种双链断裂聚集对染色体畸变的影响。
假设一个双链断裂簇内不同双链断裂之间的染色体片段太小，在畸变分析中无法检测到。采用枚举法或蒙特卡罗计算机模拟来计算许多可观察到的畸变模式的相对频率：看似简单的或明显复杂的。将理论预测结果与人类成纤维细胞的X射线数据进行比较，这些数据涉及染色体1、2、4、5、7或13的荧光原位杂交分析。
令人惊讶的是，隐匿性双链断裂多重性并不影响随机断裂和重连模型预测的畸变模式频率比。无论双链断裂是否通常以隐匿性簇的形式出现，该模型总体上与目前许多不同类型畸变的数据一致。然而，对于Revell型交换模型，预测结果确实取决于聚集构型；随着平均簇多重性增加，它们逐渐接近断裂和重连模型的预测结果。仅当在低传能线密度下也存在相当程度的双链断裂聚集，平均每个簇有大约1.5个或更多的活性双链断裂时，该模型才与数据一致，例如与明显复杂畸变与看似简单畸变的比例一致。
