Lead (Pb) is an important environmental contaminant due to its widespread use over many centuries.

While it affects primarily every organ system of the body, the most pernicious effects of Pb are on the central nervous system leading to cognitive and behavioral modification. Despite decades of research, the mechanisms responsible for Pb toxicity remain poorly understood. Recent work has suggested that Pb exposure may have consequences on chromosomal integrity as it was shown that Pb exposure leads to the generation of γH2Ax foci, a well-established biomarker for DNA double stranded break (DSB formation). As the chromosomal localization of γH2Ax foci plays an important role in determining the molecular mechanism responsible for their formation, we examined the localization of Pb-induced foci with respect to telomeres. Indeed, short or dysfunctional telomeres (uncapped or damaged telomeres) may be recognized as DSB by the DNA repair machinery, leading to “telomere-Induced Foci” (TIFs). In the current study, we show that while Pb exposure did not increase intra-chromosomal foci, it significantly induced TIFs, leading in some cases, to chromosomal abnormalities including telomere loss. The evidence suggests that these chromosomal abnormalities are likely due to perturbation of telomere replication, in particular on the lagging DNA strand. We propose a mechanism by which Pb exposure leads to the loss of telomere maintenance. As numerous studies have demonstrated a role for telomere maintenance in brain development and tissue homeostasis, our results suggest a possible mechanism for lead-induced neurotoxicity.
Citation: Pottier G, Viau M, Ricoul M, Shim G, Bellamy M, et al. (2013) Lead Exposure Induces Telomere Instability in Human Cells. PLoS ONE 8(6): e67501. doi:10.1371/journal.pone.0067501

Editor: Arthur J. Lustig, Tulane University Health Sciences Center, United States of America
Received: November 27, 2012; Accepted: May 20, 2013; Published: June 26, 2013
Copyright: © 2013 Pottier et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: M.V. is supported by the European 7th framework grant BOOSTER: grant agreement no. 242361 (http://ec.europa.eu/research/fp7/index_e​n.cfm). W.H. is supported by the European 7th framework grant DoReMi: grant agreement no. 249689 (http://ec.europa.eu/research/fp7/index_e​n.cfm). This work was supported by the grants from the Agence Nationale de la Recherche (ANR) (http://www.agence-nationale-recherche.fr​/) and the Institute National Du Cancer (INCa) (http://www.e-cancer.fr/recherche), Hemi-BREAKS and HEMIBREAKS-T. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.

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