DeSombre E R, Hughes A, Landel C C, Greene G, Hanson R, Schwartz J L
Ben May Institute, University of Chicago, IL 60637, USA.
Acta Oncol. 1996;35(7):833-40. doi: 10.3109/02841869609104034.
We studied the effect of 123I-labeled estrogen (123I-E) in estrogen receptor (ER)-rich cells in culture and in cell free model systems in vitro to elucidate the nature of the radiotoxicity for ER + cells of estrogens containing nuclides which emit Auger electrons. In cells the 123I-E caused a dose-dependent, unlabeled estrogen-inhibitable induction of chromosome aberrations. A dose of about 1000 decays per cell, which is approximately the mean lethal dose for these cells, resulted in an average of 1 chromosome break per cell. This supports the hypothesis that the lethal lesion induced by 123I-E is a chromosome break. Incubation of 123I-E/ER complex, but not 123I-E alone, with 27-mer duplex estrogen response element (ERE) DNA produced a dose-dependent cleavage of the ERE. However, we were unable to detect any fragmentation of either the 66 kDa full length ER in cell extracts or a purified 31 kDa hormone binding domain when incubated with excess 123I-E. Thus it appears that 123I-E effects its radiotoxicity by binding to ER, associating with ERE DNA and, by directing high LET radiation to DNA, inducing lethal chromosome breaks.
我们研究了123I标记的雌激素（123I-E）对培养的富含雌激素受体（ER）的细胞以及体外无细胞模型系统的影响，以阐明含发射俄歇电子核素的雌激素对ER+细胞的放射毒性本质。在细胞中，123I-E引起了剂量依赖性的、未标记雌激素可抑制的染色体畸变诱导。每细胞约1000次衰变的剂量，这大约是这些细胞的平均致死剂量，导致每细胞平均出现1次染色体断裂。这支持了123I-E诱导的致死性损伤是染色体断裂的假说。将123I-E/ER复合物（而非单独的123I-E）与27聚体双链雌激素反应元件（ERE）DNA孵育，产生了剂量依赖性的ERE切割。然而，当与过量的123I-E孵育时，我们在细胞提取物中未能检测到66 kDa全长ER或纯化的31 kDa激素结合域的任何片段化。因此，似乎123I-E通过与ER结合、与ERE DNA结合，并通过将高传能线密度辐射导向DNA，诱导致死性染色体断裂来发挥其放射毒性。
