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线性无阈模型(LNT)与癌症风险评估:其有缺陷的基础 1:辐射与白血病:LNT 的起源。

LNT and cancer risk assessment: Its flawed foundations part 1: Radiation and leukemia: Where LNT began.

机构信息

Department of Environmental Health Sciences, Morrill I, N344, University of Massachusetts, Amherst, MA, 01003, USA.

出版信息

Environ Res. 2021 Jun;197:111025. doi: 10.1016/j.envres.2021.111025. Epub 2021 Mar 18.

Abstract

This paper evaluates the scientific basis for the adoption of the linear non-threshold (LNT) dose response model for radiation-induced leukemia. This LNT risk assessment application for leukemia is significant because it: (1) was generalized for all tumor types induced by ionizing radiation and chemical carcinogens at relatively high doses and; (2) it was based on the mechanistic assumption of low dose linearity for somatic cell mutations as determined from responses in mature spermatozoa of fruit flies. A serious problem with the latter assumption is that those spermatozoa lack DNA repair. The acceptance of the LNT dose response model for cancer risk assessment was based on the convergence of recommendations of the BEAR I Genetics Panel (1956a) for reproductive cell gene mutations and those of Lewis (1957a) for somatic cell mutation and its capacity to explain apparent and/or predicted linear dose responses of ionizing radiation-induced leukemia in multiple and diverse epidemiological investigations. Use of that model and related dose response beliefs achieved rapid, widespread and enduring acceptance in the scientific and regulatory communities. They provide the key historical foundation for the sustained LNT-based policy for cancer risk assessment to the present. While previous papers in this series have challenged key scientific assessments and ethical foundations of the BEAR I Genetics Panel, the present paper provides evidence that Lewis: 1) incorrectly interpreted the fundamental scientific studies used to support the LNT conclusion even though such studies show consistent hormetic-J-shaped dose response relationships for leukemia in Hiroshima and Nagasaki survivors; and, 2) demonstrated widespread bias in support of an LNT conclusion and related policies, which kept him from making an objective and fair assessment. The LNT recommendation appears to have been uncritically accepted and integrated into scientific and regulatory practice in large part because it inappropriately appealed to existing authority and it garnered the support of those who were willing to risk greatly exaggerating the public's fears of environmentally-induced disease, such as enhanced risk of leukemia, with the goal of stopping the atmospheric testing of atomic bombs. Adoption of the LNT recommendation demonstrated extensive penetration of ideological influence affecting governmental, scientific and regulatory evaluation at the highest levels in the United States. This paper demonstrates that the scientific foundations for cancer risk assessment were inappropriately and inaccurately assessed, unethically adopted and require significant historical, scientific and regulatory remediation.

摘要

本文评估了采用线性非阈值(LNT)剂量反应模型来评估辐射诱导白血病的科学依据。这种应用于白血病的 LNT 风险评估具有重要意义,因为它:(1)适用于所有由电离辐射和化学致癌物在相对高剂量下诱导的肿瘤类型;(2)它基于体细胞突变的低剂量线性性的机制假设,该假设是从果蝇成熟精子的反应中确定的。后者假设的一个严重问题是,这些精子缺乏 DNA 修复。LNT 剂量反应模型在癌症风险评估中的接受是基于 BEAR I 遗传学小组(1956a)对生殖细胞基因突变的建议和 Lewis(1957a)对体细胞突变及其解释电离辐射诱导白血病的明显和/或预测线性剂量反应的能力的建议的趋同。该模型的使用及其相关的剂量反应信念在科学界和监管界迅速、广泛和持久地得到了接受。它们为目前基于 LNT 的癌症风险评估政策提供了关键的历史基础。虽然本系列之前的论文对 BEAR I 遗传学小组的关键科学评估和伦理基础提出了挑战,但本文提供的证据表明,Lewis:1)错误地解释了支持 LNT 结论的基础科学研究,尽管这些研究显示了广岛和长崎幸存者白血病的一致的激发生物剂量反应关系;2)表现出广泛的偏见,以支持 LNT 结论和相关政策,这使他无法进行客观和公正的评估。LNT 建议似乎未经批判性地接受并融入了科学和监管实践,在很大程度上是因为它不恰当地诉诸于现有权威,并得到了那些愿意极大地夸大公众对环境诱发疾病(如白血病风险增加)的恐惧的人的支持,目的是阻止原子弹的大气试验。LNT 建议的采用表明,意识形态影响在美国政府、科学和监管评估的最高层面上广泛渗透。本文表明,癌症风险评估的科学基础被不恰当地和不准确地评估、不道德地采用,并需要进行重大的历史、科学和监管修复。

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