Inhibition of microtubule polymerization by synthetic estrogens: formation of a ribbon structure

Dienestrol, meso-hexestrol, and rf/-hexestrol, synthetic nonsteroidal estrogens, were shown to be inhibitors of microtubule assembly in vitro using microtubule proteins isolated from porcine brains. The order of activity of the synthetic estrogens as inhibitors of microtubule assembly is: dienestrol>diethylstilbestrol>meso-hex-estrol>rf/-hexestrol>isodienestrol. The activity of dienestrol as an inhibitor was of the same order as that of (+)-griseofulvin, as determined by turbidity measure-ment. Electron microscopic observation revealed that twisted ribbon structures are formed from microtubule proteins in the presence of some synthetic estrogens (dienestrol, meso-hexestrol, and ^/-hexestrol). In a preceding paper (7), we showed that diethyl-stilbestrol (DES), a synthetic estrogen as well as a carcinogen, is an inhibitor of microtubule as-sembly in vitro. The carcinogenicity of DES, which exhibits no mutagenicity in Salmonella, could be best explained in terms of aneuploidy du