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单个α粒子穿过哺乳动物细胞核所具有的致癌转化潜能。

The oncogenic transforming potential of the passage of single alpha particles through mammalian cell nuclei.

作者信息

Miller R C, Randers-Pehrson G, Geard C R, Hall E J, Brenner D J

机构信息

Center for Radiological Research, Columbia University, 630 West 168th Street, New York, NY 10032, USA.

出版信息

Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):19-22. doi: 10.1073/pnas.96.1.19.

DOI:10.1073/pnas.96.1.19
PMID:9874764
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC15085/
Abstract

Domestic, low-level exposure to radon gas is considered a major environmental lung-cancer hazard involving DNA damage to bronchial cells by alpha particles from radon progeny. At domestic exposure levels, the relevant bronchial cells are very rarely traversed by more than one alpha particle, whereas at higher radon levels-at which epidemiological studies in uranium miners allow lung-cancer risks to be quantified with reasonable precision-these bronchial cells are frequently exposed to multiple alpha-particle traversals. Measuring the oncogenic transforming effects of exactly one alpha particle without the confounding effects of multiple traversals has hitherto been unfeasible, resulting in uncertainty in extrapolations of risk from high to domestic radon levels. A technique to assess the effects of single alpha particles uses a charged-particle microbeam, which irradiates individual cells or cell nuclei with predefined exact numbers of particles. Although previously too slow to assess the relevant small oncogenic risks, recent improvements in throughput now permit microbeam irradiation of large cell numbers, allowing the first oncogenic risk measurements for the traversal of exactly one alpha particle through a cell nucleus. Given positive controls to ensure that the dosimetry and biological controls were comparable, the measured oncogenicity from exactly one alpha particle was significantly lower than for a Poisson-distributed mean of one alpha particle, implying that cells traversed by multiple alpha particles contribute most of the risk. If this result applies generally, extrapolation from high-level radon risks (involving cellular traversal by multiple alpha particles) may overestimate low-level (involving only single alpha particles) radon risks.

摘要

在国内,低水平接触氡气被认为是一种主要的环境性肺癌危险因素,氡子体产生的α粒子会对支气管细胞造成DNA损伤。在家庭接触水平下,相关的支气管细胞很少会被一个以上的α粒子穿过,而在较高的氡水平下(铀矿工人的流行病学研究能够以合理的精度量化肺癌风险),这些支气管细胞经常会受到多个α粒子的穿过。迄今为止,在没有多次穿过带来的混杂效应的情况下,精确测量单个α粒子的致癌转化效应是不可行的,这导致了从高氡水平到家庭氡水平的风险外推存在不确定性。一种评估单个α粒子效应的技术使用带电粒子微束,它用预先定义的精确粒子数照射单个细胞或细胞核。尽管以前速度太慢,无法评估相关的小致癌风险,但最近通量的提高现在允许对大量细胞进行微束照射,从而能够首次测量单个α粒子穿过细胞核的致癌风险。在有阳性对照以确保剂量测定和生物学对照具有可比性的情况下,测量到的单个α粒子的致癌性明显低于泊松分布的单个α粒子平均值,这意味着被多个α粒子穿过的细胞贡献了大部分风险。如果这一结果普遍适用,那么从高水平氡风险(涉及多个α粒子穿过细胞)外推可能会高估低水平(仅涉及单个α粒子)氡风险。

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