The mechanism underlying the carcinogenic potential of α radiation is not fully understood, considering that cell inactivation (e.g., mitotic cell death) as a main consequence of exposure efficiently counteracts the spreading of heritable DNA damage. The aim of this study is to improve our understanding of the effectiveness of α particles in inducing different types of chromosomal aberrations, to determine the respective values of the relative biological effectiveness (RBE) and to interpret the results with respect to exposure risk. Human peripheral blood lymphocytes (PBLs) from a single donor were exposed ex vivo to doses of 0–6 Gy X rays or 0–2 Gy α particles. Cells were harvested at two different times after irradiation to account for the mitotic delay of heavily damaged cells, which is known to occur after exposure to high-LET radiation (including α particles). Analysis of the kinetics of cells reaching first or second (and higher) mitosis after irradiation and aberration data obtained by the multiplex fluorescence in situ hybridization (mFISH) technique are used to determine of the cytogenetic risk, i.e., the probability for transmissible aberrations in surviving lymphocytes. The analysis shows that the cytogenetic risk after α exposure is lower than after X rays. This indicates that the actually observed higher carcinogenic effect of α radiation is likely to stem from small scale mutations that are induced effectively by high-LET radiation but cannot be resolved by mFISH analysis.

考虑到细胞失活（例如，有丝分裂细胞死亡）作为暴露的主要后果，α 辐射的致癌潜力的潜在机制尚不完全清楚，可有效抵消可遗传的 DNA 损伤的扩散。本研究的目的是提高我们对 α 粒子诱导不同类型染色体畸变的有效性的理解，确定相对生物有效性 (RBE) 的各自值，并解释有关暴露风险的结果。来自单个供体的人外周血淋巴细胞 (PBLs) 被体外暴露0-6 Gy X 射线或 0-2 Gy α 粒子剂量。细胞在辐照后的两个不同时间收获，以解释严重受损细胞的有丝分裂延迟，这是已知在暴露于高 LET 辐射（包括 α 粒子）后发生的。细胞在照射后达到第一次或第二次（和更高次）有丝分裂的动力学分析以及通过原位多重荧光获得的畸变数据杂交 (mFISH) 技术用于确定细胞遗传风险，即存活淋巴细胞中可传播畸变的概率。分析表明，α暴露后的细胞遗传风险低于X射线后。这表明实际观察到的 α 辐射较高的致癌作用可能源于高 LET 辐射有效诱导但无法通过 mFISH 分析解决的小规模突变。