Chen A M, Lucas J N, Hill F S, Brenner D J, Sachs R K
Lawrence Livermore National Laboratory, Livermore, CA 94551, USA.
Comput Appl Biosci. 1995 Aug;11(4):389-97. doi: 10.1093/bioinformatics/11.4.389.
Monte Carlo simulations are used to analyze the reshuffling of chromosome segments which occurs when DNA is damaged by ionizing radiation. Programs are based on either Sax's classic breakage-and-reunion model or Revell's exchange model for chromosome aberrations. The simulations quantify the predictions of the two models in complete detail, using only one adjustable parameter which corresponds to total radiation dose. While testing subroutines, new analytic results on the chromosome/arm/break method of classifying aberrations were obtained. The model predictions were tested by using three-color fluorescence in situ hybridization (FISH) 'chromosome painting' on human lymphocyte cells irradiated with gamma-rays. Some of the per-cell aberration frequencies were observed to be intermediate between the predictions of the two models. This result indicates proximity 'effects', due to localization of chromosome interactions in space and time. Predictions based on chromosome arm lengths were found to be in good agreement with experiment. Monte Carlo simulations are a powerful, flexible way to compare models of chromosome aberration production with experiments quantitatively, using a minimum of theoretical presumptions.
蒙特卡罗模拟用于分析当DNA受到电离辐射损伤时发生的染色体片段重排。程序基于萨克斯的经典断裂-重聚模型或雷维尔的染色体畸变交换模型。这些模拟仅使用一个与总辐射剂量相对应的可调参数,就完整详细地量化了这两种模型的预测。在测试子程序时,获得了关于染色体/臂/断裂法分类畸变的新分析结果。通过对经γ射线照射的人类淋巴细胞进行三色荧光原位杂交(FISH)“染色体描绘”来测试模型预测。观察到一些每个细胞的畸变频率介于两种模型的预测之间。这一结果表明存在邻近“效应”,这是由于染色体相互作用在空间和时间上的局部化所致。发现基于染色体臂长度的预测与实验结果吻合良好。蒙特卡罗模拟是一种强大且灵活的方法,它使用最少的理论假设,将染色体畸变产生的模型与实验进行定量比较。