Document Detail

Structure-effect relationship in the induction of mitotic phase-specific abnormality of centrosome integrity and multipolar spindles by steroidal estrogens and their derivatives in cultured mammalian cells.
MedLine Citation:
PMID:  11566435     Owner:  NLM     Status:  MEDLINE    
In order to determine the structure-effect relationship in the induction of centrosome disintegrity (abnormality of gamma-tubulin signals) and multipolar spindles in a cultured fibroblast cell line V79 by steroidal estrogens, the activities of various estrogens and their derivatives were investigated. Induction of centrosome disintegrity by estrogens was specific in cells in the mitotic phase and was not observed in interphase cells. The centrosome disintegrity induced 24 h after exposure to estrogens was accompanied by the appearance of multinucleated cells, but the microtubule network was organized. The rank order of potency of estrogens in inducing mitotic phase-specific centrosome disintegrity and multipolar spindles was as follows: 2-methoxyestradiol>dihydroequilin 3-methyl ether=equilin 3-methyl ether>17alpha-estradiol>17beta-estradiol 3-methyl ether=17beta-estradiol>dihydroequilin>estrone 3-methyl ether. Equilin and estrone were not effective in causing centrosome disintegrity. These results suggest that the 17-hydroxyl group, irrespective of whether it is the sterically alpha or beta form, is necessary for estradiol and dihydroequilin to cause centrosome disintegrity and that O-methylation at the C-3 position was effective for equilin and dihydroequilin in enhancing the centrosome abnormality. 2-Methoxyestradiol was the most potent inducer of the centrosome disintegrity among the tested compounds and caused the induction of multiple signals of gamma-tubulin, including more than five signals.
T Ochi; T Oda
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  The Journal of steroid biochemistry and molecular biology     Volume:  78     ISSN:  0960-0760     ISO Abbreviation:  J. Steroid Biochem. Mol. Biol.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-09-21     Completed Date:  2001-11-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9015483     Medline TA:  J Steroid Biochem Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  113-22     Citation Subset:  IM    
Department of Toxicology and Environmental Health, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, 199-0195, Kanagawa, Japan.
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MeSH Terms
Carcinogens / pharmacology*
Cells, Cultured
Centrosome / drug effects*
Estrogens / pharmacology*
Microtubules / drug effects
Mitotic Index
Mitotic Spindle Apparatus / drug effects*
Steroids / pharmacology*
Structure-Activity Relationship
Toxicity Tests
Reg. No./Substance:
0/Carcinogens; 0/Estrogens; 0/Steroids

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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