Details

Autor(en) / Beteiligte

• Liamin, Marie
• Boutet-Robinet, Elisa
• Jamin, Emilien L.
• Fernier, Morgane
• Khoury, Laure
• Kopp, Benjamin
• Le Ferrec, Eric
• Vignard, Julien
• Audebert, Marc
• Sparfel, Lydie

Titel

Benzo[a]pyrene-induced DNA damage associated with mutagenesis in primary human activated T lymphocytes

Ist Teil von

• Biochemical pharmacology, 2017-08, Vol.137, p.113-124

Ort / Verlag

England: Elsevier Inc

Erscheinungsjahr

2017

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• [Display omitted] 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.