Do non-targeted effects increase or decrease low dose risk in relation to the linear-non-threshold (LNT) model?
Do non-targeted effects increase or decrease low dose risk in relation to the linear-non-threshold (LNT) model?
复制标题
非靶向效应是否会增加或减少与线性非阈值（LNT）模型有关的低剂量风险？
DOI：
10.1016/j.mrfmmm.2010.01.008
复制
发表时间：
2010-05-01
影响因子：
2.3
通讯作者：
Little, M. P.
中科院分区：
文献类型：
--
作者：
Little, M. P.
关键词：
在本文中，我们回顾了恶性和非恶性疾病偏离线性的证据，并根据这一点评估可能的机制，特别是非靶向效应的潜在作用。在日本原子弹爆炸幸存者和许多在医疗和职业上受到低剂量或中等剂量照射的群体中观察到的过高癌症风险在统计学上基本一致。对于大多数癌症部位，这些组中的剂量反应与观察到的范围内的线性一致。关于生物机制的现有数据并不普遍支持低剂量阈值或毒物兴奋效应的观点。大量的证据并没有表明，实际上在统计学上与癌症的任何非常大的剂量阈值或可能的激素效应不一致，并且几乎没有证据表明非DNA靶向效应暗示的反应中的非线性。日本原子弹爆炸幸存者和其他群体患各种非恶性疾病的风险也很高。特别是，在原子弹数据中观察到心血管疾病、呼吸系统疾病和消化系统疾病的风险增加。与癌症相比，不同受照群体之间的风险模式的一致性要小得多;例如，在这些其他（非原子弹）群体中没有发现与辐射有关的呼吸道和消化道疾病。在许多接触人群中，特别是在医疗接触人群中发现了心血管风险，但与癌症相比，不同研究之间的风险一致性要低得多：流行病学研究中每单位剂量的风险至少相差两个数量级，这可能是众所周知的（但未观察到的）风险因素造成的混淆和影响改变的结果。在流行病学证据缺乏令人信服的机制解释的情况下，目前，不太有说服力，对报告的心血管疾病统计关联的因果解释是不可靠的，但不能排除。炎症过程是最有可能的机制，辐射可以修改动脉粥样硬化疾病的过程。如果低剂量电离辐射通过这一机制改变心血管疾病，则不能排除非DNA靶效应的作用。
In this paper we review the evidence for departure from linearity for malignant and non-malignant disease and in the light of this assess likely mechanisms, and in particular the potential role for non-targeted effects. Excess cancer risks observed in the Japanese atomic bomb survivors and in many medically and occupationally exposed groups exposed at low or moderate doses are generally statistically compatible. For most cancer sites the dose–response in these groups is compatible with linearity over the range observed. The available data on biological mechanisms do not provide general support for the idea of a low dose threshold or hormesis. This large body of evidence does not suggest, indeed is not statistically compatible with, any very large threshold in dose for cancer, or with possible hormetic effects, and there is little evidence of the sorts of non-linearity in response implied by non-DNA-targeted effects. There are also excess risks of various types of non-malignant disease in the Japanese atomic bomb survivors and in other groups. In particular, elevated risks of cardiovascular disease, respiratory disease and digestive disease are observed in the A-bomb data. In contrast with cancer, there is much less consistency in the patterns of risk between the various exposed groups; for example, radiation-associated respiratory and digestive diseases have not been seen in these other (non-A-bomb) groups. Cardiovascular risks have been seen in many exposed populations, particularly in medically exposed groups, but in contrast with cancer there is much less consistency in risk between studies: risks per unit dose in epidemiological studies vary over at least two orders of magnitude, possibly a result of confounding and effect modification by well known (but unobserved) risk factors. In the absence of a convincing mechanistic explanation of epidemiological evidence that is, at present, less than persuasive, a cause-and-effect interpretation of the reported statistical associations for cardiovascular disease is unreliable but cannot be excluded. Inflammatory processes are the most likely mechanism by which radiation could modify the atherosclerotic disease process. If there is to be modification by low doses of ionizing radiation of cardiovascular disease through this mechanism, a role for non-DNA-targeted effects cannot be excluded.
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DOI：
10.1073/pnas.70.6.1753
发表时间：
1973-01-01
影响因子：
11.1
作者：
BENDITT, EP;BENDITT, JM
通讯作者：
BENDITT, JM
DOI：
10.1016/j.mrfmmm.2004.10.003
发表时间：
2005-02-15
影响因子：
2.3
作者：
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影响因子：
3.4
作者：
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Trosko, JE
影响因子：
8.8
作者：
DARBY, SC;DOLL, R;SMITH, PG
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SMITH, PG
影响因子：
3.4
作者：
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