Inhibition of estrogen-receptor-DNA interaction by intercalating drugs.

Ethidium bromide, an intercalating drug, was shown to inhibit the in vitro DNA binding of the uterine estradiol-receptor complex. The inhibition was reversible, dose dependent, complete for total saturation of DNA intercalating sites by the dye, and proportional to the extent of intercalated drug. The binding of the receptor to phosphocellulose and poly(adenylic acid)-cellulose was not decreased by this drug. Similar inhibition was also obtained with 9-hydroxyellipticine. Denatured DNA was more efficient at binding the estrogen receptor than phosphocellulose or poly(adenylic acid)-cellulose but less efficient than native DNA. We conclude that the DNA binding of the estrogen receptor cannot be simply interpreted in terms of electrostatic interactions but requires a particular double-helical structure of DNA.