Cellular and subcellular studies of the radiation effects of Auger electron-emitting estrogens.
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.
DeSombre
E R
ER
Ben May Institute, University of Chicago, IL 60637, USA. gdesombr@ben-may.bsd.uchicago.edu
Hughes
A
A
Landel
C C
CC
Greene
G
G
Hanson
R
R
Schwartz
J L
JL
D000818:Animals; D016466:CHO Cells / Q000737:chemistry / Q000528:radiation effects; D002869:Chromosome Aberrations; D006224:Cricetinae; D004249:DNA Damage; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology*; D007457:Iodine Radioisotopes / Q000378:metabolism; D018499:Linear Energy Transfer; D011829:Radiation Dosage; D011960:Receptors, Estrogen / Q000528:radiation effects*
D004967:Estrogens; D007457:Iodine Radioisotopes; D011960:Receptors, Estrogen