Radiation risk to low fluences of alpha particles may be greater than we thought.
Radiation risk to low fluences of alpha particles may be greater than we thought.
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DOI：
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发表时间：
2001
影响因子：
11.1
通讯作者：
H. Zhou;M. Suzuki;G. Randers-Pehrson;D. Vannais;G. Chen;J. Trosko;C. Waldren;T. Hei
中科院分区：
文献类型：
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作者：
H. Zhou;M. Suzuki;G. Randers-Pehrson;D. Vannais;G. Chen;J. Trosko;C. Waldren;T. Hei
国际辐射防护委员会（辐射防护委员会）和美国辐射防护和测量全国理事会（辐射防护委员会）主要根据在广岛和长崎投下的原子弹幸存者中发现的癌症发病率，建议使用线性、无阈值模型从较高剂量推断低剂量照射的癌症风险估计数。这一建议所依据的理论是，细胞核的DNA是辐射引起的遗传毒性的主要目标，随着直接受损的细胞减少，辐射的有害影响也相应减少。在本文中，我们使用精密微束来靶向融合群体中的确切比例（100%或<或=20%）的细胞，并分别用恰好一个α粒子照射它们的细胞核。我们发现，在一些已知的细胞核部分被击中的人群中，诱导突变和染色体变化的频率与非击中细胞对反应的贡献是一致的。事实上，用单个α粒子/细胞照射10%的汇合哺乳动物细胞群体导致突变体产量类似于当群体中的所有细胞被照射时观察到的突变体产量。在用1 mM剂量的辛醇（其抑制间隙连接介导的细胞间通讯）预处理的细胞中，或在携带显性阴性连接蛋白43载体的细胞中，这种效应显著消除。这些数据意味着辐射诱变的相关目标大于单个细胞，并表明需要重新考虑线性外推法在对低剂量、高线性能量转移（LET）辐射照射进行风险估计时的有效性。
Based principally on the cancer incidence found in survivors of the atomic bombs dropped in Hiroshima and Nagasaki, the International Commission on Radiation Protection (ICRP) and the United States National Council on Radiation Protection and Measurements (NCRP) have recommended that estimates of cancer risk for low dose exposure be extrapolated from higher doses by using a linear, no-threshold model. This recommendation is based on the dogma that the DNA of the nucleus is the main target for radiation-induced genotoxicity and, as fewer cells are directly damaged, the deleterious effects of radiation proportionally decline. In this paper, we used a precision microbeam to target an exact fraction (either 100% or < or =20%) of the cells in a confluent population and irradiated their nuclei with exactly one alpha particle each. We found that the frequencies of induced mutations and chromosomal changes in populations where some known fractions of nuclei were hit are consistent with non-hit cells contributing significantly to the response. In fact, irradiation of 10% of a confluent mammalian cell population with a single alpha particle per cell results in a mutant yield similar to that observed when all of the cells in the population are irradiated. This effect was significantly eliminated in cells pretreated with a 1 mM dose of octanol, which inhibits gap junction-mediated intercellular communication, or in cells carrying a dominant negative connexin 43 vector. The data imply that the relevant target for radiation mutagenesis is larger than an individual cell and suggest a need to reconsider the validity of the linear extrapolation in making risk estimates for low dose, high linear-energy-transfer (LET) radiation exposure.