Site-specific covalent binding of stilbene-type and steroidal estrogens to tubulin following metabolic activation in vitro.
Both the steroidal estrogen, 2-hydroxy estradiol, and the stilbene-type estrogen, diethylstilbestrol, bind covalently and selectively to the C-terminal domain of beta-tubulin after peroxidative activation in vitro. The binding probably has to be attributed to quinonoid metabolites, as estrogens such as estradiol and hexestrol, which are unable to form quinones under these conditions, fail to bind. Albumin is not simultaneously modified, demonstrating the selectivity of the binding. The observed protein binding is discussed with respect to estrogen-induced aneuploidy and neoplastic cell transformation.
Epe
B
B
Hegler
J
J
Metzler
M
M
D001665:Binding Sites; D001711:Biotransformation; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004054:Diethylstilbestrol / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism; D011485:Protein Binding; D013381:Subtilisins / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism*
D014404:Tubulin; D004958:Estradiol; D004054:Diethylstilbestrol; D004247:DNA; C001390:2-hydroxyestradiol; D013381:Subtilisins