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<title lang=en>Human T lymphocytes bioactivate heterocyclic aromatic amines by forming DNA adducts</title>
<creator>Bellamri, Medjda</creator>
<creator>Le Hegarat, Ludovic</creator>
<creator>Vernhet, Laurent</creator>
<creator>Baffet, Georges</creator>
<creator>Turesky, Robert J.</creator>
<creator>Langouët, Sophie</creator>
<contributor>Agence Nationale de Sécurité Sanitaire, de l'Alimentation, de l'environnement et du Travail (ANSES) ; ANSES</contributor>
<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>University of Minnesota [Minneapolis]</contributor>
<description>International audience</description>
<source>ISSN: 0893-6692</source>
<source>Environmental and Molecular Mutagenesis</source>
<publisher>Wiley-Blackwell</publisher>
<identifier>hal-01400486</identifier>
<identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01400486</identifier>
<source>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01400486</source>
<source>Environmental and Molecular Mutagenesis, Wiley-Blackwell, 2016, 57 (9), pp.656 - 667. 〈10.1002/em.22059〉</source>
<identifier>DOI : 10.1002/em.22059</identifier>
<relation>info:eu-repo/semantics/altIdentifier/doi/10.1002/em.22059</relation>
<identifier>PUBMED : 27801952</identifier>
<relation>info:eu-repo/semantics/altIdentifier/pmid/27801952</relation>
<language>en</language>
<subject lang=en>2-amino-9H-pyrido[2</subject>
<subject lang=en>3-b]indole</subject>
<subject lang=en>carcinogen metabolism</subject>
<subject lang=en>cytochrome P450</subject>
<subject lang=en>genotoxicity</subject>
<subject>[SDV.GEN] Life Sciences [q-bio]/Genetics</subject>
<type>info:eu-repo/semantics/article</type>
<type>Journal articles</type>
<description lang=en>Heterocyclic aromatic amines (HAA) are formed in cooked meat, poultry and fish but also arise in tobacco smoke and exhaust gases. HAA are potential human carcinogens, which require metabolic activation to exert their genotoxicity. Human tissues can bioactivate HAA to produce reactive intermediates that bind to DNA. HAA DNA adduct formation occurs in human hepatocytes; however, the potential of HAA to form DNA adducts has not been investigated in human T lymphocytes. In this study, we investigated the ability of human T lymphocytes activated with PMA/Ionomycin or CD3/CD28 to express functional CYP1 activity and bioactivate three major HAA: 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-9H-pyrido[2,3-b]indole (AαC) to form DNA adducts. Adducts were measured by ultraperformance liquid chromatography-electrospray ionization/multistage scan mass spectrometry. The highest level of DNA adducts occurred for AαC (16 adducts per 109 nucleotides), followed by PhIP (9 adducts per 109 nucleotides). In contrast, DNA adducts formed from MeIQx and the structurally related aromatic amine 4-aminobiphenyl, a known human carcinogen, were below the limit of detection (< 3 adducts per 109 nucleotides). Moreover, we demonstrate that AαC is a potent inducer of CYP1A1 and CYP1B1 activity through a transcriptional mechanism involving the AhR pathway. Overall, our results highlight the capacity of activated human T lymphocytes to more efficiently bioactivate AαC to form DNA adducts than other prominent HAA or 4-ABP. Environ. Mol. Mutagen. 57:656-667, 2016.</description>
<date>2016</date>
</dc>
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