DNA and Chromosome Breaks Induced by Iodine- 123-Labeled Estrogen in Chinese Hamster Ovary Cells

The effects of the Auger electron-emitting isotope¹²³ I 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 the¹²³ I-labeled estrogen induced both single- and double-strand breaks with a ratio of single- to double-strand breaks of 2.8. The corresponding ratio with⁶⁰ Co γ 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 the¹²³ I-labeled estrogen. The¹²³ I-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 of¹²³ I-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 that¹²³ I-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 that¹²³ I bound to estrogen is an efficient clastogenic agent, the cytotoxic damage produced by¹²³ I bound to estrogen is very like damage induced by high-LET radiation, and the¹²³ I in the estrogen receptor-DNA complex is probably in proximity to the sugarphosphate backbone of the DNA.