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Carboxylate polystyrene nanoplastics disrupt mitotic progression and induce chromosomal instability
Summary
Researchers found that carboxylate polystyrene nanoplastics accumulated near centrosomes in cells and induced supernumerary centrioles, leading to abnormal spindle formation and chromosomal instability during cell division, revealing a mechanism by which nanoplastics may cause heritable genetic damage.
The widespread use of plastics has raised serious concerns regarding environmental pollution and human health. Although exposure to nanoplastics induces significant toxicities, the mechanisms underlying their genotoxicity, particularly chromosomal instability, remain poorly understood. In this study, we used a non-lethal dose of carboxylate polystyrene nanoplastics (cPS-NPs), which have high reactivity with biological molecules due to enhanced surface reactivity. cPS-NPs accumulated near the centrosomes, inducing supernumerary centrioles accompanied by reduced Aurora kinase A activity. These abnormal centrosomes nucleate excessively stable and hyperpolymerized microtubules, resulting in erroneous kinetochore-microtubule attachments with merotelic and syntelic configurations. Cells treated with cPS-NPs failed to correct these attachment errors, likely due to compromised spindle assembly checkpoints and/or impaired tension sensing, as indicated by the reduced recruitment of Mad2 and BuR1 and low activity of Aurora kinase B and Polo-like kinase 1 to the kinetochores. Consequently, the cells underwent prolonged metaphase, during which excessive pulling forces from the hyperstabilized microtubules triggered premature sister chromatid separation. Persistent misattachments result in misaligned and lagging chromosomes, which can lead to the formation of micronuclei, a widely used marker of genotoxicity. Our findings indicated that a non-lethal dose of cPS-NPs can disrupt mitotic progression. Furthermore, we propose that abnormalities in the centrosomes, microtubules, and chromosomes could serve as potential markers for assessing genotoxicity following acute exposure to a non-lethal dose of nanoplastics.
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