Department of Environmental Health Sciences, University of Massachusetts, Morrill I, N344, Amherst, MA, 01003, USA.
Retired From Oak Ridge National Laboratory at Oak Ridge, TN, 4088 Nottinghill Gate Road, Upper Arlington, OH, 43220, USA.
Arch Toxicol. 2024 Aug;98(8):2731-2737. doi: 10.1007/s00204-024-03808-0. Epub 2024 Jun 23.
This paper reevaluates the first report of X-ray-induced somatic gene mutations. It was undertaken by John Patterson, Department Chair of Hermann Muller, using the same biological model, methods and equipment of Muller. Patterson reported X-ray induced mutation frequencies for X-chromosome-linked (sex-linked) recessive gene mutations in somatic cells of Drosophila melanogaster that resulted in color changes in the ommatidia of the eyes. Results were based on color changes detected in both male and female offspring irradiated while in egg, larval or pupal stages and for unirradiated controls. Patterson claimed that the observed dose response displayed linearity, with a clear implication that the linear response extended to background exposure levels of unirradiated controls. This reanalysis disputes Patterson's interpretation, showing that the dose response in the low-dose zone strongly supported a threshold model. The doses in the experiment, which were not clearly presented, were so high that it would preclude the assumption that the experiment provided any information of relevance to radiation exposures of humans at low doses, or even at high doses delivered at low-dose rates. Induced phenotypical changes that occurred at the higher doses, especially in female offspring, overwhelmingly resulted from X-ray-induced chromosome breaks instead of point mutations as initially expected by Patterson. The Patterson findings and linearity interpretations were an important contributory factor in the acceptance of the linear non-threshold (LNT) model during the formative time of concept consolidation. It is rather shocking now to see that the actual data provided no support for the LNT model.
这篇论文重新评估了首次关于 X 射线诱导体基因突变的报告。该报告由赫尔曼·穆勒(Hermann Muller)部门主席约翰·帕特森(John Patterson)撰写,他使用了与穆勒相同的生物学模型、方法和设备。帕特森报告了 X 射线诱导的性连锁(伴性)隐性基因突变频率,这些突变发生在黑腹果蝇(Drosophila melanogaster)的体细胞中,导致眼睛的小眼发生颜色变化。结果基于雄性和雌性后代在卵、幼虫或蛹期受到照射以及未受照射对照的颜色变化检测得出。帕特森声称,观察到的剂量反应呈线性,这清楚地表明线性反应扩展到未受照射对照的背景暴露水平。这项重新分析对帕特森的解释提出了质疑,表明低剂量区的剂量反应强烈支持阈值模型。实验中的剂量没有明确说明,但非常高,这排除了实验提供了与人类低剂量辐射暴露或甚至低剂量率高剂量暴露相关的任何信息的假设。在更高剂量下发生的诱导表型变化,尤其是在雌性后代中,绝大多数是由 X 射线诱导的染色体断裂引起的,而不是最初预期的由帕特森引起的点突变。帕特森的发现和线性解释是在概念整合的形成时期接受线性非阈值(LNT)模型的一个重要促成因素。现在看到实际数据并没有为 LNT 模型提供支持,这令人震惊。