Hande M Prakash, Azizova Tamara V, Burak Ludmilla E, Khokhryakov Valentin F, Geard Charles R, Brenner David J
Center for Radiological Research, Columbia University Medical Center, New York, USA.
Genes Chromosomes Cancer. 2005 Sep;44(1):1-9. doi: 10.1002/gcc.20217.
Long-lived, sensitive, and specific biomarkers of particular mutagenic agents are much sought after and potentially have broad applications in the fields of cancer biology, epidemiology, and prevention. Many clastogens induce a spectrum of chromosome aberrations, and some of them can be exploited as biomarkers of exposure. Densely ionizing radiation, for example, alpha particle radiation (from radon or plutonium) and neutron radiation, preferentially induces complex chromosome aberrations, which can be detected by the 24-color multifluor fluorescence in situ hybridization (mFISH) technique. We report the detection and quantification of stable complex chromosome aberrations in lymphocytes of healthy former nuclear-weapons workers, who were exposed many years ago to plutonium, gamma rays, or both, at the Mayak weapons complex in Russia. We analyzed peripheral-blood lymphocytes from these individuals for the presence of persistent complex chromosome aberrations. A significantly elevated frequency of complex chromosome translocations was detected in the highly exposed plutonium workers but not in the group exposed only to high doses of gamma radiation. No such differences were found for simple chromosomal aberrations. The results suggest that stable complex chromosomal translocations represent a long-lived, quantitative, low-background biomarker of densely ionizing radiation for human populations exposed many years ago.
人们一直在寻找特定诱变剂的长寿命、敏感且特异的生物标志物,其在癌症生物学、流行病学和预防领域可能具有广泛应用。许多致断裂剂会诱发一系列染色体畸变,其中一些可被用作暴露生物标志物。例如,高电离辐射,如α粒子辐射(来自氡或钚)和中子辐射,优先诱发复杂染色体畸变,可通过24色多荧光原位杂交(mFISH)技术检测到。我们报告了对健康的前苏联核武器工作者淋巴细胞中稳定复杂染色体畸变的检测和定量,这些工作者多年前在俄罗斯马亚克武器联合体接触过钚、γ射线或两者。我们分析了这些个体外周血淋巴细胞中持续存在的复杂染色体畸变情况。在高度暴露于钚的工作者中检测到复杂染色体易位频率显著升高,但仅暴露于高剂量γ辐射的组中未检测到。简单染色体畸变未发现此类差异。结果表明,稳定的复杂染色体易位代表了多年前暴露人群中高电离辐射的长寿命、定量、低背景生物标志物。