The comparative radiation genetics of humans and mice.
The comparative radiation genetics of humans and mice.
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人类和小鼠的比较辐射遗传学。
DOI：
10.1146/annurev.ge.24.120190.001551
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发表时间：
1990
影响因子：
11.1
通讯作者：
Lewis,SE
中科院分区：
文献类型：
--
作者：
Neel,JV;Lewis,SE
遗传学家试图预测人类暴露于电离辐射的遗传后果，可以说是他们在过去半个世纪中面临的最严肃的社会责任之一。这个问题本身很重要，它也可以作为评估人类对我们物种生存环境的其他扰动对我们自己的最终遗传影响的努力的原型。最近，我们（67-69）一直在撰写论文，根据对原子弹爆炸幸存者子女的研究结果，人类对辐射的遗传效应可能不像各个委员会根据最常用的范例（实验室小鼠）的数据所预测的那样敏感（参见12、104、105）。在这篇综述中，我们尝试在空间允许的情况下对人类和小鼠的研究结果进行尽可能详细的比较，以一种能够使那些在论证中的某些关键点希望做出其他假设的人能够这样做的方式呈现数据。我们认为，重新考虑包括现有的所有小鼠数据，可以使小鼠双倍剂量的估计与基于人类的较高估计令人满意地一致。由于双倍剂量的概念在这些讨论中至关重要，因此从一开始就需要一个明确的定义。遗传双倍辐射剂量是对群体产生与每一代自发发生的相同突变影响的急性或慢性辐射量。为了与社会相关，该估计最好用发病率和死亡率来表达。对于自发突变和诱导突变，通常参考第一代效应。这个定义原则上涵盖了DNA中所有可能改变的影响，从单核苷酸取代和非常小的插入和缺失到整个染色体的获得或丢失。定义很简单，概念也很有用。将遗传损伤表示为双倍剂量提供了方便的社会参考框架。
The attempt by geneticists to predict the genetic consequences for humans of exposure to ionizing radiation has arguably been one of the most serious social responsibilities they have faced in the past half century. Important for its own sake, this issue also serves as a prototype for the effort to evaluate the ultimate genetic impact on ourselves of other human perturbations of the environment in which our species functions. Recently we (67–69) have been developing the thesis that according to the results of studies on the children of survivors of the atomic bombings, humans may not be as sensitive to the genetic effects of radiation as has been projected by various committees on the basis of data from the most commonly employed paradigm, the laboratory mouse (cf 12, 104, 105). In this review we attempt as detailed a comparison as space permits of the findings on humans and mice, presenting the data in a fashion that will enable those who at certain critical points in the argument wish to make other assumptions, to do so. We argue that a reconsideration that includes all the data now available on mice brings the estimate of the doubling dose for mice into satisfactory agreement with the higher estimate based on humans.Since the concept of a doubling dose is critical in these discussions, a clear definition is needed at the outset. The genetic doubling dose of radiation is the amount of acute or chronic radiation that will produce the same mutational impact on a population as occurs spontaneously each generation. To be societally relevant, that estimate is best expressed in terms of morbidity and mortality. For both spontaneous and induced mutation, the reference is customarily first generation effects. This definition in principle encompasses the impact of the gamut of all possible alterations in DNA, from single nucleotide substitutions and very small insertions and deletions to gain or loss of entire chromosomes. The definition is as simple as the concept is useful. Expressing genetic damage as a doubling dose provides a convenient societal frame of reference.