Deshpande A, Goodwin E H, Bailey S M, Marrone B L, Lehnert B E
Life Sciences Division, Los Alamos National Laboratory, New Mexico 87545, USA.
Radiat Res. 1996 Mar;145(3):260-7.
We investigated the relationship between nuclear hits by alpha particles and the subsequent occurrence of sister chromatid exchanges (SCEs) in normal human diploid lung fibroblasts (HFL1). Cells were exposed to 238Pu alpha particles at doses ranging from 0.4-12.9 cGy and subsequently analyzed for SCEs. A significant increase in SCE frequency was observed even at the lowest dose examined. The extent of induction of SCEs in the HFL1 cells showed dose dependency in the very low dose range, i.e. 0.4-2.0 cGy. Thereafter, induction of SCEs was independent of dose. Based on measurements of the nuclear areas of the HFL1 cells in conjunction with target theory calculations, the lowest dose resulted in an approximately 8.6-fold increase in the percentage of cells showing excessive SCEs over the theoretically expected percentage of cells whose nuclei were calculated to be traversed by one or more alpha particles. The extent of the discrepancies between theoretically expected and experimentally observed frequencies of SCEs became progressively reduced with increasing radiation dose. We additionally determined that SCEs induced by the alpha particles have no significant dependency on the time of cell collection after exposure to a selected dose of alpha particles, thereby confirming that the differences between the theoretically predicted and observed SCE frequencies were not due to an artifact of the time of cell sampling for the SCE measurements. These results obtained with normal human cells are similar to those of other investigators who observed excessive SCEs in immortalized rodent cells beyond that which could be attributed exclusively to nuclear traversals by alpha particles. Such consistent findings point to the existence of an alternative, extranuclear target through which alpha particles cause DNA damage, as detected by SCE analysis. The existence of an extranuclear compartment as a target for alpha particles may have important implications for the susceptibility of lung cells to the DNA-damaging effects of alpha-particle exposure due to the inhalation of radon progeny.
我们研究了α粒子对正常人类二倍体肺成纤维细胞（HFL1）的核撞击与随后姐妹染色单体交换（SCE）发生之间的关系。将细胞暴露于剂量范围为0.4 - 12.9 cGy的238Puα粒子下，随后分析SCE情况。即使在检测的最低剂量下，也观察到SCE频率显著增加。在非常低的剂量范围（即0.4 - 2.0 cGy）内，HFL1细胞中SCE的诱导程度呈现剂量依赖性。此后，SCE的诱导与剂量无关。基于对HFL1细胞核面积的测量并结合靶理论计算，最低剂量导致显示过度SCE的细胞百分比比理论预期的、其细胞核被计算为被一个或多个α粒子穿过的细胞百分比增加了约8.6倍。随着辐射剂量增加，理论预期和实验观察到的SCE频率之间的差异程度逐渐减小。我们还确定，α粒子诱导的SCE对暴露于选定剂量α粒子后细胞收集时间没有显著依赖性，从而证实理论预测和观察到的SCE频率之间的差异不是由于SCE测量时细胞采样时间的人为因素造成的。这些在正常人类细胞中获得的结果与其他研究者的结果相似，他们在永生化啮齿动物细胞中观察到了超出仅由α粒子核穿行所导致的过度SCE。这些一致的发现表明存在一个额外的、核外靶点，通过该靶点α粒子会导致DNA损伤，这可通过SCE分析检测到。作为α粒子靶点的核外区室的存在可能对肺细胞因吸入氡子体而对α粒子暴露的DNA损伤效应的易感性具有重要意义。
