Hahnfeldt P, Hlatky L R, Brenner D J, Sachs R K
Joint Center for Radiation Therapy, Harvard Medical School, Boston, Massachusetts 02115.
Radiat Res. 1995 Feb;141(2):136-52.
Most chromosome aberrations produced by ionizing radiation develop from DNA double-strand breaks (DSBs). Published data on the yield and variance of excess acentric fragments after in vitro irradiation of human lymphocytes were compared with corresponding data on dicentrics. At low LET the number of excess acentric fragments is about 60% of the number of dicentrics, independent of dose and perhaps of dose rate, suggesting that dicentrics and excess acentric fragments arise from similar kinetics rather than from fundamentally different reactions. Only a weak dependence of the ratio on LET is observed. These results are quantified using generalizations of models for pairwise DSB interactions suggested by Brewen and Brock based on data for marsupial cells. By allowing singly incomplete and some "doubly incomplete" exchanges, the models can also account for the experimental observation that the dispersion for excess acentric fragments, a measure of cell-to-cell variance, is systematically larger than the dispersion for dicentrics. Numerical estimates of an incompleteness parameter are derived.
电离辐射产生的大多数染色体畸变源自DNA双链断裂(DSB)。将已发表的关于人淋巴细胞体外照射后多余无着丝粒片段的产额和方差的数据,与双着丝粒的相应数据进行了比较。在低传能线密度(LET)下,多余无着丝粒片段的数量约为双着丝粒数量的60%,与剂量无关,可能也与剂量率无关,这表明双着丝粒和多余无着丝粒片段源自相似的动力学,而非根本不同的反应。仅观察到该比率对LET有微弱的依赖性。利用Brewen和Brock基于有袋类动物细胞数据提出的成对DSB相互作用模型的推广形式,对这些结果进行了量化。通过允许单重不完全和一些“双重不完全”交换,这些模型还可以解释实验观察结果,即作为细胞间方差度量的多余无着丝粒片段的离散度,系统性地大于双着丝粒的离散度。得出了不完全性参数的数值估计。