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<datestamp>2017-12-21</datestamp>
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<title lang=en>Benzo[a]pyrene-induced DNA damage associated with mutagenesis in primary human activated T lymphocytes</title>
<creator>Liamin, Marie</creator>
<creator>Boutet-Robinet, Elisa</creator>
<creator>Jamin, Emilien L.</creator>
<creator>Fernier, Morgane</creator>
<creator>Khoury, Laure</creator>
<creator>Kopp, Benjamin</creator>
<creator>Le Ferrec, Eric</creator>
<creator>Vignard, Julien</creator>
<creator>Audebert, Marc</creator>
<creator>Sparfel, Lydie</creator>
<contributor>Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor>
<contributor>ToxAlim (ToxAlim) ; Institut National Polytechnique [Toulouse] (INP) - Institut National de la Recherche Agronomique (INRA) - Université Paul Sabatier - Toulouse 3 (UPS) - Ecole Nationale Vétérinaire de Toulouse</contributor>
<contributor>The French National Research Program for Environmental and Occupational Health of ANSES</contributor>
<contributor> Cancer TMOI of the French National Alliance for Life and Health Sciences (AVIESAN) [2014/1/052]</contributor>
<contributor> ANSES</contributor>
<description>International audience</description>
<source>ISSN: 0006-2952</source>
<source>Biochemical Pharmacology</source>
<publisher>Elsevier</publisher>
<identifier>hal-01560145</identifier>
<identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560145</identifier>
<identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560145/document</identifier>
<identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560145/file/Liamin%20et%20al.%20-%20Benzo%5Ba%5Dpyrene-induced%20DNA%20damage%20associated%20with%20.pdf</identifier>
<source>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560145</source>
<source>Biochemical Pharmacology, Elsevier, 2017, 137, pp.113-124. 〈10.1016/j.bcp.2017.04.025〉</source>
<identifier>DOI : 10.1016/j.bcp.2017.04.025</identifier>
<relation>info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bcp.2017.04.025</relation>
<identifier>PUBMED : 28461126</identifier>
<relation>info:eu-repo/semantics/altIdentifier/pmid/28461126</relation>
<language>en</language>
<subject lang=en>activated human t lymphocytes</subject>
<subject lang=en> benzo[a]pyrene</subject>
<subject lang=en> dna damage response</subject>
<subject>[SDV.TOX.ECO] Life Sciences [q-bio]/Toxicology/Ecotoxicology</subject>
<type>info:eu-repo/semantics/article</type>
<type>Journal articles</type>
<description lang=en>Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (B[a]P), are widely distributed environmental contaminants exerting toxic effects such as genotoxicity and carcinogenicity, mainly associated with aryl hydrocarbon receptor (AhR) activation and the subsequent induction of cytochromes P-450 (CYP) 1-metabolizing enzymes. We previously reported an up-regulation of AhR expression and activity in primary cultures of human T lymphocyte by a physiological activation. Despite the suggested link between exposure to PAHs and the risk of lymphoma, the potential of activated human T lymphocytes to metabolize AhR exogenous ligands such as B[a]P, and produce DNA damage has not been investigated. In the present study, we characterized the genotoxic response of primary activated T lymphocytes to B[a] P. We demonstrated that, following T lymphocyte activation, B[a]P treatment triggers a marked increase in CYP1 expression and activity generating, upon metabolic activation, DNA adducts and double-strand breaks (DSBs) after a 48-h treatment. At this time point, B[a]P also induces a DNA damage response with ataxia telangiectasia mutated kinase activation, thus producing a p53-dependent response and T lymphocyte survival. B[a]P activates DSB repair by mobilizing homologous recombination machinery but also induces gene mutations in activated human T lymphocytes which could consequently drive a cancer process. In conclusion, primary cultures of activated human T lymphocytes represent a good model for studying genotoxic effects of environmental contaminants such as PAHs, and predicting human health issues. </description>
<date>2017</date>
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