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Abstract Title:

Airborne particulate matter induces mitotic slippage and chromosomal missegregation through disruption of the spindle assembly checkpoint (SAC).

Abstract Source:

Chemosphere. 2019 Jul 1 ;235:794-804. Epub 2019 Jul 1. PMID: 31280048

Abstract Author(s):

Miguel Santibáñez-Andrade, Yesennia Sánchez-Pérez, Yolanda I Chirino, Rocío Morales-Bárcenas, Luis A Herrera, Claudia M García-Cuellar

Article Affiliation:

Miguel Santibáñez-Andrade

Abstract:

Particulate matter (PM) is a risk factor for lung cancer development and chromosomal missegregation and cell cycle disruptions are key cellular events that trigger tumorigenesis. We aimed to study the effect of PM(PM with an aerodynamic diameter≤10 μm) on mitotic arrest and chromosomal segregation, evaluating the spindle assembly checkpoint (SAC) protein dynamics in the human lung A549 adenocarcinoma cell line. For this purpose, synchronized cells were exposed to PMfor 24 h to obtain the frequency of micronucleated (MN) and trinucleated (TN) cells. Then, the efficiency of the mitotic arrest after PMexposure was analyzed. To elucidate the effect of PMin chromosomal segregation, the levels and subcellular localization of essential SAC proteins were evaluated. Results indicated that A549 cells exposed to PMexhibited an increase in MN and TN cells and a decrease in mitotic indexes and G2/M phase. A549 cells treated with PMshowed reduced protein levels of MDC1 and NEK2 (38% and 35% respectively), which is required for MAD2 recruitment to kinetochores, MAD2 and BUBR1, effectors of the SAC (25% and 18% respectively), and CYCLIN B1, required during G2/M phase (35%). Besides, PMexposure increase the levels of AURORA B and SURVIVIN, required for SAC activation through chromosome-microtubule attachment errors (85% and 74% respectively). We suggest that PMcauses mitotic slippage due to alterations in MAD2 localization. Thus, PMcauses inadequate chromosomal segregation and deficient mitotic arrest by altering SAC protein levels, predisposing A549 cells to chromosomal instability, a common feature observed in cancer.

Study Type : In Vitro Study

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