A model of chromosome aberration induction and chronic myeloid leukaemia incidence at low doses
A model of chromosome aberration induction and chronic myeloid leukaemia incidence at low doses
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DOI：
10.1007/s00411-004-0246-7
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发表时间：
2004-09-01
影响因子：
1.7
通讯作者：
Ottolenghi, A
中科院分区：
文献类型：
--
作者：
Ballarini, F;Ottolenghi, A
一些染色体畸变类型，通常是易位，与特定的癌症相关。一个例子是慢性髓性白血病（CML）细胞，其中大多数携带涉及9号染色体上的ABL基因和22号染色体上的BCR基因的易位。CML和BCR-ABL易位的嵌合蛋白产物之间存在因果关系的假说最近得到了有力的支持。在这个框架内，一个机制模型和蒙特-卡罗代码模拟辐射诱导的人类淋巴细胞染色体畸变。该模型的当前版本可以预测的剂量-反应曲线的主要畸变类型急性照射后的γ射线和轻离子的不同能量。该模型是基于这样的假设，即只有成簇的DNA病变可以导致畸变，只有病变的自由端在相邻的染色体领土可以加入和形成交换。这种损伤根据辐射轨迹结构分布在细胞核内，即对于低LET辐射是随机的，而对于高LET轻离子是沿着直线分布的。间期染色体领土明确模拟和背景畸变考虑在内。非常好的协议被发现与实验数据取自文献，提供了进一步验证的模型。作为应用，计算了BCR-ABL易位的产率。初步结果导致CML诱导剂量-反应在低于0.1戈伊时近似为二次方，在高达1戈伊的较高剂量下基本上呈线性。CML诱导的概率得到的数值与其他组用不同方法得到的值一致。
Some chromosome aberration types, generally translocations, are correlated with specific cancers. An example is provided by chronic myeloid leukemia (CML) cells, most of which carry a translocation involving the ABL gene on chromosome 9 and the BCR gene on chromosome 22. The hypothesis of a causal relationship between CML and the chimeric protein product of the BCR-ABL translocation has recently received strong support. In this framework, a mechanistic model and Monte-Carlo code simulating radiation-induced chromosome aberrations in human lymphocytes will be presented. The current version of the model can predict dose-response curves for the main aberration types following acute irradiation with gamma rays and light ions of different energies. The model is based on the assumption that only clustered DNA lesions can lead to aberrations and that only lesion free ends in neighbouring chromosome territories can join and form exchanges. Such lesions are distributed within the cell nucleus according to the radiation track structure, i.e. randomly for low-LET radiation and along straight lines for high-LET light ions. Interphase chromosome territories are explicitly simulated and background aberrations are taken into account. Very good agreement was found with experimental data taken from the literature that provided a further validation of the model. As an application, yields of BCR-ABL translocations were calculated. Preliminary results led to a CML induction dose-response that is approximately quadratic below 0.1 Gy and essentially linear at higher doses up to 1 Gy. The numerical values obtained for the probability of CML induction are consistent with values obtained by other groups with different approaches.