Cellular and subcellular studies of the radiation effects of Auger electron-emitting estrogens.
Acta Oncol
; 35(7): 833-40, 1996.
Article
em En
| MEDLINE
| ID: mdl-9004760
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
Receptores de Estrogênio
/
Aberrações Cromossômicas
/
Transferência Linear de Energia
/
Estrogênios
/
Radioisótopos do Iodo
Limite:
Animals
Idioma:
En
Revista:
Acta Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Estados Unidos