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Article

Aluminum Enters Mammalian Cells and Destabilizes Chromosome Structure and Number

1
Laboratoire de Cancérogenèse Environnementale, Fondation des Grangettes, 1224 Chêne-Bougeries, Switzerland
2
Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK
*
Author to whom correspondence should be addressed.
Academic Editors: Hans J. Lipps and Jan Postberg
Int. J. Mol. Sci. 2021, 22(17), 9515; https://doi.org/10.3390/ijms22179515
Received: 30 April 2021 / Revised: 20 August 2021 / Accepted: 26 August 2021 / Published: 1 September 2021
(This article belongs to the Special Issue Nuclear Architecture in Differentiation and Diseases)
Chromosome instability (CIN) consists of high rates of structural and numerical chromosome abnormalities and is a well-known hallmark of cancer. Aluminum is added to many industrial products of frequent use. Yet, it has no known physiological role and is a suspected human carcinogen. Here, we show that V79 cells, a well-established model for the evaluation of candidate chemical carcinogens in regulatory toxicology, when cultured in presence of aluminum—in the form of aluminum chloride (AlCl3) and at concentrations in the range of those measured in human tissues—incorporate the metal in a dose-dependent manner, predominantly accumulating it in the perinuclear region. Intracellular aluminum accumulation rapidly leads to a dose-dependent increase in DNA double strand breaks (DSB), in chromosome numerical abnormalities (aneuploidy) and to proliferation arrest in the G2/M phase of the cell cycle. During mitosis, V79 cells exposed to aluminum assemble abnormal multipolar mitotic spindles and appear to cluster supernumerary centrosomes, possibly explaining why they accumulate chromosome segregation errors and damage. We postulate that chronic aluminum absorption favors CIN in mammalian cells, thus promoting carcinogenesis. View Full-Text
Keywords: aluminium; metal; lumogallion aluminium; metal; lumogallion
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MDPI and ACS Style

Tenan, M.R.; Nicolle, A.; Moralli, D.; Verbouwe, E.; Jankowska, J.D.; Durin, M.-A.; Green, C.M.; Mandriota, S.J.; Sappino, A.-P. Aluminum Enters Mammalian Cells and Destabilizes Chromosome Structure and Number. Int. J. Mol. Sci. 2021, 22, 9515. https://doi.org/10.3390/ijms22179515

AMA Style

Tenan MR, Nicolle A, Moralli D, Verbouwe E, Jankowska JD, Durin M-A, Green CM, Mandriota SJ, Sappino A-P. Aluminum Enters Mammalian Cells and Destabilizes Chromosome Structure and Number. International Journal of Molecular Sciences. 2021; 22(17):9515. https://doi.org/10.3390/ijms22179515

Chicago/Turabian Style

Tenan, Mirna R., Adeline Nicolle, Daniela Moralli, Emeline Verbouwe, Julia D. Jankowska, Mary-Anne Durin, Catherine M. Green, Stefano J. Mandriota, and André-Pascal Sappino. 2021. "Aluminum Enters Mammalian Cells and Destabilizes Chromosome Structure and Number" International Journal of Molecular Sciences 22, no. 17: 9515. https://doi.org/10.3390/ijms22179515

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