Effect of Benzo[a]Pyrene on Spindle Misorientation and Fidelity of Chromosome Segregation in Lung Epithelial BEAS-2B Cells

Jose Thaiparambil, Oula Mansour, Randa El-Zein

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Benzo[a]pyrene (B[a]P) is an environmental carcinogen found in tobacco smoke. It leads to high levels of DNA adducts in the lungs of cigarette smokers contributing to genomic instability. Alterations in the mitotic spindle apparatus play a major role in the generation of genomic instability through promoting chromosome mis-segregation and aneuploidy. To date, the effect of B[a]P exposure on altering the mitotic apparatus in normal lung epithelial cells remains unknown. In our study, BEAS-2B human bronchial epithelial cells were exposed to B[a]P and spindle dynamics were evaluated. Confocal imaging showed that B[a]P exposure significantly alters spindles misorientation, leading to chromosome mis-segregations in the form of chromosome lags and bridges. In addition, centrosome duplication and premature centriole disengagement were induced leading to misaligned and multipolar spindle formation. Comparative genomic analysis of mitotic spindle associated genes, revealed downregulation of AurA-Plk1-AurB signaling cascade by B[a]P. In addition, we analyzed the status of p53 and its downstream p21 in B[a]P-treated cells and showed a suppression of p53-p21 axis. When the extent of DNA damage associated with induced mitotic abnormalities was investigated using γ-H2AX, a significant increase and persistence in DNA damage was observed. Overall, our findings show that B[a]P potently induces mitotic abnormalities, DNA damage, and genetic instability.

Original languageEnglish (US)
Pages (from-to)167-176
Number of pages10
JournalToxicological sciences : an official journal of the Society of Toxicology
Volume162
Issue number1
Early online dateNov 6 2017
DOIs
StatePublished - Mar 1 2018

Keywords

  • Journal Article

ASJC Scopus subject areas

  • Toxicology

Fingerprint Dive into the research topics of 'Effect of Benzo[a]Pyrene on Spindle Misorientation and Fidelity of Chromosome Segregation in Lung Epithelial BEAS-2B Cells'. Together they form a unique fingerprint.

Cite this