Chadwick K H
Cowan Head, Kendal, United Kingdom.
J Radiol Prot. 2017 Jun 26;37(2):422-433. doi: 10.1088/1361-6498/aa6722. Epub 2017 May 10.
The aim of this article is to offer a broader, mechanism-based, analytical tool than that used by (Rühm et al 2016 Ann. ICRP 45 262-79) for the interpretation of cancer induction relationships. The article explains the limitations of this broader analytical tool and the implications of its use in view of the publications by Leuraud et al 2015 (Lancet Haematol. 2 e276-81) and Richardson et al 2015 (Br. Med. J. 351 h5359). The publication by Rühm et al 2016 (Ann. ICRP 45 262-79), which is clearly work in progress, reviews the current status of the dose and dose-rate effectiveness factor (DDREF) as recommended by the ICRP. It also considers the issues which might influence a reassessment of both the value of the DDREF as well as its application in radiological protection. In this article, the problem is approached from a different perspective and starts by commenting on the limited scientific data used by Rühm et al 2016 (Ann. ICRP 45 262-79) to develop their analysis which ultimately leads them to use a linear-quadratic dose effect relationship to fit solid cancer mortality data from the Japanese life span study of atomic bomb survivors. The approach taken here includes more data on the induction of DNA double strand breaks and, using experimental data taken from the literature, directly relates the breaks to cell killing, chromosomal aberrations and somatic mutations. The relationships are expanded to describe the induction of cancer as arising from radiation induced cytological damage coupled to cell killing since the cancer mutated cell has to survive to express its malignant nature. Equations are derived for the induction of cancer after both acute and chronic exposure to sparsely ionising radiation. The equations are fitted to the induction of cancer in mice to illustrate a dose effect relationship over the total dose range. The 'DDREF' derived from the two equations varies with dose and the DDREF concept is called into question. Although the equation for acute exposure can be used to analyse atomic bomb survivor data, the fitting is dominated by the quadratic dose component. Thus, little useful information can be derived about the linear dose component which is important for the derivation of low dose rate risk. The ICRP are advised to derive the risk at low dose rates from epidemiological studies of, for example, worker populations, together with information from cellular radiation biological research.
本文的目的是提供一种比(Rühm等人,2016年,《国际辐射防护委员会年报》45卷,262 - 79页)所使用的更广泛的、基于机制的分析工具,用于解释癌症诱发关系。本文解释了这种更广泛分析工具的局限性,以及鉴于Leuraud等人2015年(《柳叶刀·血液学》2卷,e276 - 81页)和Richardson等人2015年(《英国医学杂志》351卷,h5359页)的出版物,使用该工具的影响。Rühm等人2016年(《国际辐射防护委员会年报》45卷,262 - 79页)的出版物显然仍在完善中,它回顾了国际辐射防护委员会推荐的剂量和剂量率有效性因子(DDREF)的现状。它还考虑了可能影响重新评估DDREF值及其在辐射防护中应用的问题。在本文中,从不同的角度探讨了这个问题,首先评论了Rühm等人2016年(《国际辐射防护委员会年报》45卷,262 - 79页)用于开展其分析的有限科学数据,这些数据最终导致他们使用线性 - 二次剂量效应关系来拟合原子弹爆炸幸存者日本寿命研究中的实体癌死亡率数据。这里采用的方法纳入了更多关于DNA双链断裂诱导的数据,并利用文献中的实验数据,直接将这些断裂与细胞杀伤、染色体畸变和体细胞突变联系起来。这些关系得到扩展,以描述癌症的诱发是由于辐射诱导的细胞学损伤与细胞杀伤相结合,因为癌症突变细胞必须存活才能表现出其恶性特征。推导了急性和慢性暴露于低线性能量传递辐射后癌症诱发的方程。这些方程与小鼠癌症诱发情况进行拟合,以说明在总剂量范围内的剂量效应关系。从这两个方程得出的“DDREF”随剂量变化,DDREF概念受到质疑。尽管急性暴露方程可用于分析原子弹爆炸幸存者数据,但拟合主要由二次剂量成分主导。因此,对于推导低剂量率风险很重要的线性剂量成分,几乎无法得出有用信息。建议国际辐射防护委员会从例如工人人群的流行病学研究以及细胞辐射生物学研究的信息中推导低剂量率风险。