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

International audiencePolycyclic 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

Landscape Evolution and Human Settlement in the Iroise Sea (Brittany, France) during the Neolithic and Bronze Age

International audienceThe Molène archipelago appears to be particularly rich in Neolithic and Bronze Age remains and an exceptional concentration of megaliths has been brought to light. Several settlements are confirmed by dry-stone structures or by shell middens. These data give precious indications on the occupation chronology of the area. Moreover they allow us, for the first time in Brittany, to reconstruct everyday life during the late Prehistoric period.A prerequisite to this reconstruction was a better understanding of the evolution of the environment during this period, which locally implies a better knowledge of paleogeographic changes related to Holocene sea-level rise as well as on floral and faunal resources. The results obtained through paleogeographic reconstructions show that the archipelago since 4500 BC was already disconnected from the mainland. The megalithic monuments must therefore have been erected and used by islanders present on the archipelago from the middle of the 5th to the 2nd millennium BC. The distribution of the megalithic tombs reveals landscape occupation strategies which respond to both cultural choices and natural constraints. Throughout the entire period, geographic isolation has continued to increase, although it did not imply strong cultural specificities. Nevertheless, the increasing remoteness of the islands has fostered the search for livelihoods based on the intense exploitation of coastal resources. Despite their focus on the sea, these people did not neglect what inland areas could offer as evidenced by the early agro-pastoral practices in the archipelago