CELLULAR AND SUBCELLULAR STUDIES OF THE RADIATION EFFECTS OF AUGER ELECTRON-EMITTING ESTROGENS

We studied the effect of I-123-labeled estrogen (I-123-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 e strogens containing nuclides which emit Auger electrons. In cells the I-123-E caused a dose-dependent, unlabeled estrogen-inhibitable induct ion of chromosome aberrations. A dose of about 1 000 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 hypoth esis that the lethal lesion induced by I-123-E is a chromosome break, Incubation of I-123-E/ER complex, but not I-123-E alone, with 27-mer d uplex estrogen response element (ERE) DNA produced a dose-dependent cl eavage 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 I-123-E. Thus i t appears that I-123-E effects its radiotoxicity by binding to ER, ass ociating with ERE DNA and, by directing high LET radiation to DNA, ind ucing lethal chromosome breaks.