DNA and chromosome breaks induced by iodine-123-labeled estrogen in Chinese hamster ovary cells.
The effects of the Auger electron-emitting isotope 123I, covalently bound to estrogen, on DNA single- and double-strand breakage and on chromosome breakage was determined in estrogen receptor-positive Chinese hamster ovary (CHO-ER) cells. Exposure to the 123I-labeled estrogen induced both single- and double-strand breaks with a ratio of single- to double-strand breaks of 2.8. The corresponding ratio with 60Co gamma rays was 15.6. The dose response was biphasic, suggesting either that receptor sites are saturated at high doses, or that there is a nonrandom distribution of breaks induced by the 123I-labeled estrogen. The 123I-labeled estrogen treatment induced chromosome aberrations with an efficiency of about 1 aberration for each 1000 disintegrations per cell. This corresponds to the mean lethal dose of 123I-labeled estrogen for these cells, suggesting that the lethal event induced by the Auger electron emitter bound to estrogen is a chromosome aberration. Most of the chromosome-type aberrations were dicentrics and rings, suggesting that 123I-labeled estrogen-induced chromosome breaks are rejoined. The F ratio, the ratio of dicentrics to centric rings, was 5.8 +/- 1.7, which is similar to that seen with high-LET radiations. Our results suggest that 123I bound to estrogen is an efficient clastogenic agent, the cytotoxic damage produced by 123I bound to estrogen is very like damage induced by high-LET radiation, and the 123I in the estrogen receptor-DNA complex is probably in proximity to the sugar-phosphate backbone of the DNA.
Schwartz
J L
JL
Center for Mechanistic Biology and Biotechnology, Argonne National Laboratory, Illinois 60439-4833, USA.
Mustafi
R
R
Hughes
A
A
DeSombre
E R
ER
D000818:Animals; D016466:CHO Cells; D002869:Chromosome Aberrations; D006224:Cricetinae; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004967:Estrogens / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D018499:Linear Energy Transfer; D011960:Receptors, Estrogen / Q000032:analysis
D004967:Estrogens; D007457:Iodine Radioisotopes; D011960:Receptors, Estrogen; D004247:DNA