Underprediction of visibly complex chromosome aberrations by a recombinational-repair ('one-hit') model.
Underprediction of visibly complex chromosome aberrations by a recombinational-repair ('one-hit') model.
复制标题
重组修复（“一次性”）模型对明显复杂的染色体畸变的预测不足。
DOI：
10.1080/095530000138790
复制
发表时间：
2000
影响因子：
2.6
通讯作者：
Hlatky,LR
中科院分区：
文献类型：
--
作者：
Sachs,RK;Rogoff,A;Chen,AM;Simpson,PJ;Savage,JR;Hahnfeldt,P;Hlatky,LR
目的利用已发表的低LET荧光原位杂交（low-LET FISH）数据，对基于断裂-再结合和重组修复的两种染色体畸变模型进行检验。材料与方法综合分析DNA双链断裂诱导和错接的随机性，并将其作为工作假设。邻近效应近似使用相互作用网站。模型结果计算使用CAS（染色体畸变模拟器）蒙特卡罗计算机软件与两个可调参数。CAS可以模拟任何实验绘画协议的细节，允许非常详细的测试models.ResultsTo合理的近似，断裂和团聚模型预测是一致的低LET FISH结果，包括两个大的，精心制作的，一个油漆数据集。一个明确规定的版本的重组修复模型严重低估了频率的明显复杂的畸变模式最常见的单漆FISH观察，并与一些观察到的多油漆模式不一致。当高剂量效应（畸变和饱和）被定量考虑时，尽管在2-6Gy.ConclusionsThe随机断裂和团聚模型在剂量范围内近似线性，但对于明显简单的互换的剂量-响应关系稍微有利于断裂和团聚模型，而不是重组-修复模型。这些数据反对这里讨论的随机重组修复途径形成的复杂畸变。
PurposePublished low-LET FISH data were used to test two models of chromosome aberration production based on breakage-and-reunion or recombinational repair.Materials and methodsRandomness of DNA double strand break induction and misrejoining is analyzed comprehensively and adopted as a working hypothesis. Proximity effects are approximated by using interaction sites. Model results are calculated using CAS (chromosome aberration simulator) Monte Carlo computer software with two adjustable parameters. CAS can emulate the specifics of any experimental painting protocol, allowing very detailed tests of the models.ResultsTo reasonable approximation, breakage-and-reunion model predictions are consistent with low-LET FISH results, including two large, elaborate, one-paint data sets. An explicitly specified version of the recombinational-repair model severely underpredicts the frequency of the visibly complex aberration patterns most commonly observed with one-paint FISH, and is inconsistent with some observed multi-paint patterns. When high-dose effects (distortion and saturation) are taken into account quantitatively, a dose-response relation for apparently simple interchanges slightly favours the breakage-and-reunion model over the recombinational-repair model, despite being approximately linear over the dose range 2-6Gy.ConclusionsThe random breakage-and-reunion model gives comprehensive baseline predictions that are sufficiently accurate for the organization of experimental results. The data speak against complex aberrations being formed by the random recombinational repair pathway discussed here.