Treatment-time-dependence models of early and delayed radiation injury in rat small intestine
Treatment-time-dependence models of early and delayed radiation injury in rat small intestine
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DOI：
10.1016/s0360-3016(00)00708-2
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发表时间：
2000-10-01
影响因子：
7
通讯作者：
Langberg, CW
中科院分区：
文献类型：
--
作者：
Denham, JW;Hauer-Jensen, M;Langberg, CW
背景资料：本研究模拟了一系列实验的数据，这些实验最初是为了研究局部照射后时间、剂量和分割对大鼠小肠早期和晚期病理终点的影响。其目的是获得令人满意的描述的再生反应损伤连同早期和晚期endpoints.Methods之间可能的关系：两个和26周的病理辐射损伤数据组的Sprague-Dawley大鼠照射与27个不同的分馏时间表建模使用不完全修复（IR）版本的线性二次模型，或没有各种时间校正模型。测试了以下时间校正模型：（1）无时间校正;（2）在开始治疗后的任意时间开始的简单指数（SE）再生反应;和（3）双指数反应，其开始与累积的细胞消耗和级分大小相关（“智能响应模型”[INTR]），通过将每个剂量组的预测生物有效剂量与观察到的辐射损伤相关联，评估各种模型的拟合优度score.Results:（1）没有时间校正的不完全修复模型不能对2周或26周的数据提供令人满意的描述。(2)使用SE时间校正的模型表现更好，提供了适度的数据描述。(3)INTR模型提供了2周和26周数据的合理描述，证实了早期和晚期病理终点的治疗时间依赖性。（4）当再生反应假设在照射后2周而不是在照射结束时停止时，通过INTR模型获得了最令人满意的数据描述。在最佳拟合模型中，再生反应的分数大小依赖性延迟也被建议。(5)晚期终点与低分馏敏感性和治疗时间依赖性，即使在动物组表现出最小的早期粘膜reactions.Conclusion：放射损伤评分在此大鼠小肠实验模型不能充分描述没有时间校正。“后果”机制有助于发展晚期效应，即使在没有发展严重的早期粘膜损伤的动物中也是如此。再生反应的启动受到分数大小依赖性有丝分裂延迟的影响，并与累积的细胞消耗水平有关。这种反应在治疗结束时不会停止，但可能会持续到最大程度的愈合。(C)2000 Elsevier Science Inc.
Background: The present study modeled data from a large series of experiments originally designed to investigate the influence of time, dose, and fractionation on early and late pathologic endpoints in rat small intestine after localized irradiation. The objective was to obtain satisfactory descriptions of the regenerative response to injury together with the possible relationships between early and late endpoints.Methods: Two- and 26-week pathologic radiation injury data in groups of Sprague-Dawley rats irradiated with 27 different fractionation schedules were modeled using the incomplete repair (IR) version of the linear-quadratic model with or without various time correction models. The following time correction models were tested: (1) No time correction; (2) A simple exponential (SE) regenerative response beginning at an arbitrary time after starting treatment; and (3) A bi-exponential response with its commencement linked to accumulated cellular depletion and fraction size (the 'intelligent response model' [INTR]), Goodness of fit of the various models was assessed by correlating the predicted biological effective dose for each dose group with the observed radiation injury score.Results: (1) The incomplete repair model without time correction did not provide a satisfactory description of either the 2- or 26-week data. (2) The models using SE time correction performed better, providing modest descriptions of the data. (3) The INTR model provided reasonable descriptions of both the 2- and 26-week data, confirming a treatment time dependence of both early and late pathological endpoints, (4) The most satisfactory descriptions of the data by the INTR model were obtained when the regenerative response was assumed to cease 2 weeks after irradiation rather than at the end of irradiation. A fraction-size-dependent delay of the regenerative response was also suggested in the best fitting models. (5) Late endpoints were associated with low-fractionation sensitivity and treatment-time dependence even in animal groups that exhibited minimal early mucosal reactions.Conclusion: Radiation injury scores in this rat small intestinal experimental model cannot be adequately described without time correction. 'Consequential' mechanisms contribute to the development of late effects, even in animals that do not develop severe early mucosal injuries. The initiation of the regenerative response is subject to a fraction size-dependent mitotic delay and is linked to the level of accumulated cellular depletion. The response does not cease at the end of therapy but probably continues until maximal healing has taken place. (C) 2000 Elsevier Science Inc.