First report of X-ray induced somatic mutation by Muller’s department chair fails to support Muller’s linearity hypothesis

IF 4.8 2区 医学 Q1 TOXICOLOGY
Edward Calabrese, Paul B. Selby
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Abstract

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.

Abstract Image

穆勒的系主任首次报告了 X 射线诱导的体细胞突变,但未能支持穆勒的线性假说。
本文重新评估了第一份关于 X 射线诱导体细胞基因突变的报告。该研究由赫尔曼-穆勒的系主任约翰-帕特森(John Patterson)利用与穆勒相同的生物模型、方法和设备进行。帕特森报告了黑腹果蝇体细胞中 X 染色体连锁(性连锁)隐性基因突变的 X 射线诱导突变频率,这些突变导致眼睛的膜质发生颜色变化。研究结果基于在卵期、幼虫期或蛹期接受辐照的雄性和雌性后代以及未接受辐照的对照组中检测到的颜色变化。帕特森声称,观察到的剂量反应呈线性关系,这显然意味着线性反应延伸到了未受辐照对照组的背景辐照水平。这次重新分析对帕特森的解释提出了质疑,显示低剂量区的剂量反应强烈支持阈值模型。该实验中的剂量没有明确提出,但其剂量之高,使人无法假定该实验提供了任何与低剂量人体辐照相关的信息,甚至无法假定该实验提供了任何与低剂量高剂量率人体辐照相关的信息。在较高剂量下发生的表型变化,特别是在雌性后代中,绝大多数是由 X 射线引起的染色体断裂造成的,而不是帕特森最初预期的点突变。帕特森的发现和线性解释是线性非阈值(LNT)模型在概念形成巩固时期被接受的一个重要促成因素。现在看来,实际数据并没有为 LNT 模型提供任何支持,这一点相当令人震惊。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Archives of Toxicology
Archives of Toxicology 医学-毒理学
CiteScore
11.60
自引率
4.90%
发文量
218
审稿时长
1.5 months
期刊介绍: Archives of Toxicology provides up-to-date information on the latest advances in toxicology. The journal places particular emphasis on studies relating to defined effects of chemicals and mechanisms of toxicity, including toxic activities at the molecular level, in humans and experimental animals. Coverage includes new insights into analysis and toxicokinetics and into forensic toxicology. Review articles of general interest to toxicologists are an additional important feature of the journal.
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