Abstract：
:There is increasing concern that animal and human reproduction may be adversely affected by exposure to xenoestrogens that activate estrogen receptors. There is evidence that one such compound, Bisphenol A (BPA), also induces meiotic and mitotic aneuploidy, suggesting that these kinds of molecules may also have effects on cell division. In an effort to understand how Bisphenol A might disrupt cell division, a phenotypic analysis was carried out using sea urchin eggs, whose early embryonic divisions are independent of zygotic transcription. Fertilized Lytechinus pictus eggs exposed to BPA formed multipolar spindles resulting in failed cytokinesis in a dose-dependent, transcriptionally independent manner. By use of novel biotinylated BPA affinity probes to fractionate cell-free extracts, tubulin was identified as a candidate binding protein by mass spectrometry, and BPA promoted microtubule polymerization and centrosome-based microtubule nucleation in vitro but did not appear to display microtubule-stabilizing activity. Treatment of mammalian cells demonstrated that BPA as well as a series of Bisphenol A derivatives induced ectopic spindle pole formation in the absence of centrosome overduplication. Together, these results suggest a novel mechanism by which Bisphenol A affects the nucleation of microtubules, disrupting the tight spatial control associated with normal chromosome segregation, resulting in aneuploidy.
journal_name
ACS Chem Bioljournal_title
ACS chemical biologyauthors
George O,Bryant BK,Chinnasamy R,Corona C,Arterburn JB,Shuster CBdoi
10.1021/cb700210usubject
Has Abstractpub_date
2008-03-20 00:00:00pages
167-79issue
3eissn
1554-8929issn
1554-8937journal_volume
3pub_type
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