ECB-ART-40594
ACS Chem Biol
2008 Mar 20;33:167-79. doi: 10.1021/cb700210u.
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Bisphenol A directly targets tubulin to disrupt spindle organization in embryonic and somatic cells.
George O
,
Bryant BK
,
Chinnasamy R
,
Corona C
,
Arterburn JB
,
Shuster CB
.
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.
PubMed ID: 18225860
PMC ID: PMC3844426
Article link: ACS Chem Biol
Grant support: [+]
R25 GM061222 NIGMS NIH HHS , S06 GM008136 NIGMS NIH HHS , GM61222 NIGMS NIH HHS , S06 GM08136 NIGMS NIH HHS , P20 RR16480 NCRR NIH HHS , P20 RR016480 NCRR NIH HHS
Genes referenced: LOC100887844 LOC115919910 pole tubgcp2
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