Induction of multiple microtubule-organizing centers, multipolar spindles and multipolar division in cultured V79 cells exposed to diethylstilbestrol, estradiol-17beta and bisphenol A.
Inducibility of multipolar spindles and multipolar division by diethylstilbestrol (DES) and estradiol-17beta (E2) was investigated in terms of the mechanism of induction of aneuploidy by the estrogens. DES, E2 and bisphenol A (Bp-A), a structural analogue of DES, caused mitotic arrest and aberrant spindles, such as tripolar and multipolar spindles, in a concentration-dependent manner. Gamma-tubulin, a well-characterized component of microtubule-organizing centers (MTOCs), was co-localized with the aberrant spindles induced by estrogens and Bp-A. The number of gamma-tubulin signals in the mitotic cells coincided with that of the aberrant spindles and rose with an increasing concentration of the chemicals. The incidence and location of gamma-tubulin in interphase cells were not influenced by the chemicals. These results suggest that multiple MT nucleating sites were induced by the estrogens and Bp-A during the transition from interphase to the mitotic phase. DES, E2 and Bp-A induced multipolar division in a concentration-dependent process associated with the induction of aneuploidy.
Ochi
T
T
Department of Toxicology and Environmental Health, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan. tkfmochi@pharm.teikyo-u.ac.jp
D000782:Aneuploidy; D000818:Animals; D001559:Benzhydryl Compounds; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D002875:Chromosomes / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D008168:Lung / Q000166:cytology / Q000187:drug effects; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D008940:Mitotic Index / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology*; D008941:Spindle Apparatus / Q000187:drug effects / Q000235:genetics* / Q000648:ultrastructure; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004054:Diethylstilbestrol; D004958:Estradiol; D004968:Estrogens, Non-Steroidal; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds