Department of Environmental Health Sciences, Morrill I, N344, University of Massachusetts, Amherst, MA 01003, USA.
Environ Res. 2017 Oct;158:773-788. doi: 10.1016/j.envres.2017.07.030. Epub 2017 Jul 27.
The LNT single-hit model was derived from the Nobel Prize-winning research of Herman J. Muller who showed that x-rays could induce gene mutations in Drosophila and that the dose response for these so-called mutational events was linear. Lewis J. Stadler, another well-known and respected geneticist at the time, strongly disagreed with and challenged Muller's claims. Detailed evaluations by Stadler over a prolonged series of investigations revealed that Muller's experiments had induced gross heritable chromosomal damage instead of specific gene mutations as had been claimed by Muller at his Nobel Lecture. These X-ray-induced alterations became progressively more frequent and were of larger magnitude (more destructive) with increasing doses. Thus, Muller's claim of having induced discrete gene mutations represented a substantial speculative overreach and was, in fact, without proof. The post hoc arguments of Muller to support his gene mutation hypothesis were significantly challenged and weakened by a series of new findings in the areas of cytogenetics, reverse mutation, adaptive and repair processes, and modern molecular methods for estimating induced genetic damage. These findings represented critical and substantial limitations to Muller's hypothesis of X-ray-induced gene mutations. Furthermore, they challenged the scientific foundations used in support of the LNT single-hit model by severing the logical nexus between Muller's data on radiation-induced inheritable alterations and the LNT single-hit model. These findings exposed fundamental scientific flaws that undermined not only the seminal recommendation of the 1956 BEAR I Genetics Panel to adopt the LNT single-hit Model for risk assessment but also any rationale for its continued use in the present day.
LNT 单击模型源自诺贝尔生理学或医学奖得主赫尔曼·J·穆勒（Herman J. Muller）的研究，他表明 X 射线可以诱导果蝇中的基因突变，并且这些所谓的突变事件的剂量反应呈线性。当时另一位著名且备受尊敬的遗传学家刘易斯·J·斯塔德勒（Lewis J. Stadler）强烈反对并质疑穆勒的说法。斯塔德勒（Stadler）经过长时间的一系列调查进行了详细的评估，结果表明，穆勒的实验诱导了严重的可遗传染色体损伤，而不是像他在诺贝尔奖演讲中声称的那样诱导了特定的基因突变。这些 X 射线诱导的改变变得越来越频繁，并且随着剂量的增加，其幅度（破坏性更大）也越来越大。因此，穆勒声称诱导了离散的基因突变，这代表了一个实质性的过度推测，实际上没有证据。穆勒为支持其基因突变假说而提出的事后论点，受到了细胞遗传学、反向突变、适应和修复过程以及现代分子方法估计诱导遗传损伤等领域的一系列新发现的显著挑战和削弱。这些发现代表了对穆勒关于 X 射线诱导基因突变假说的关键和实质性限制。此外，它们通过切断穆勒关于放射性遗传改变的数据与 LNT 单击模型之间的逻辑联系，挑战了支持 LNT 单击模型的科学依据。这些发现暴露了基础性的科学缺陷，不仅破坏了 1956 年 BEAR I 遗传学小组提出采用 LNT 单击模型进行风险评估的开创性建议，而且还破坏了其在当今继续使用的任何理由。
