In Vitro Study of Mutagenesis Induced by Crocidolite-Exposed Alveolar Macrophages NR8383 in Cocultured Big Blue Rat2 Embryonic Fibroblasts

Asbestos-induced mutagenicity in the lung may involve reactive oxygen/nitrogen species (ROS/RNS) released by alveolar macrophages. With the aim of proposing an alternative in vitro mutagenesis test, a coculture system of rat alveolar macrophages (NR8383) and transgenic Big Blue Rat2 embryonic fibroblasts was developed and tested with a crocidolite sample. Crocidolite exposure induced no detectable increase in ROS production from NR8383, contrasting with the oxidative burst that occurred following a brief exposure (1 hour) to zymosan, a known macrophage activator. In separated cocultures, crocidolite and zymosan induced different changes in the gene expressions involved in cellular inflammation in NR8383 and Big Blue. In particular, both particles induced up-regulation of iNOS expression in Big Blue, suggesting the formation of potentially genotoxic nitrogen species. However, crocidolite exposure in separated or mixed cocultures induced no mutagenic effects whereas an increase in Big Blue mutants was detected after exposure to zymosan in mixed cocultures. NR8383 activation by crocidolite is probably insufficient to induce in vitro mutagenic events. The mutagenesis assay based on the coculture of NR8383 and Big Blue cannot be used as an alternative in vitro method to assess the mutagenic properties of asbestos fibres

Archaeology of the Pleistocene-Holocene transition in Portugal: synthesis and prospects

The Tardiglacial of Portugal has been associated with the Magdalenian culture and lithic industries characterized by tool miniaturization, a diversity of microlith types, and the absence of a intentional blade production. The technological characterization, the chronology and the phasing of the Portuguese Magdalenian have been defined based on data recovered from open-air sites of the Estremadura region (Central Portugal). This paper presents an overview of the research undertaken over the last twenty-five years, including results from research and preventive archaeology fieldwork outside this region, namely in the Côa, Sabor and Vouga Valleys (northern Portugal), as well as in the Guadiana Valley and Algarve regions (southern Portugal). Our chronological boundaries are the Greenland Stadial 2-1b and the 8.2 ka event, from Early Magdalenian to Early Mesolithic. Regarding vegetation, deciduous Quercus underwent expansion during the warm phases of the Tardiglacial and retracted during cold ones, when pines increased. After the Solutrean, the faunal assemblages show a decrease in the variability of the represented species and an increase in fish, birds, small mammals and rabbits (Oryctolagus cuniculus). Concerning the cultural sequence, the Middle Magdalenian remains uncharacterised. After the Upper Magdalenian, and thenceforward, the use of local raw materials and of cores-on-flakes (burin or carinated endscraper type) for bladelet production gradually increased. In terms of lithic armatures typology, a four-stage sequence can be discerned: 1) Upper Magdalenian with axial points rather than backed bladelets, quite common in previous phases; 2) Final Magdalenian with an increase in the diversity of armature types; 3) Azilian with geometric microliths, curved backed points (Azilian points) and Malaurie points, and 4) Early Mesolithic without retouched bladelet tools or at best a persistence of Azilian armature types. There were some changes in the Palaeolithic rock art of the Douro basin between phase 3 (Final Magdalenian) and phase 4 (Late Azilian): figurative animal representations give place to animal depictions characterized by their geometrical bodies, often filled-in, and red deer becomes the best-represented animal.FCT: PTDC/EPH-ARQ/0326/2014info:eu-repo/semantics/publishedVersio

Crocidolite-Exposed Alveolar Macrophages NR8383 in Cocultured Big Blue Rat2 Embryonic Fibroblasts

Asbestos-induced mutagenicity in the lung may involve reactive oxygen/nitrogen species (ROS/RNS) released by alveolar macrophages. With the aim of proposing an alternative in vitro mutagenesis test, a coculture system of rat alveolar macrophages (NR8383) and transgenic Big Blue Rat2 embryonic fibroblasts was developed and tested with a crocidolite sample. Crocidolite exposure induced no detectable increase in ROS production from NR8383, contrasting with the oxidative burst that occurred following a brief exposure (1 hour) to zymosan, a known macrophage activator. In separated cocultures, crocidolite and zymosan induced different changes in the gene expressions involved in cellular inflammation in NR8383 and Big Blue. In particular, both particles induced up-regulation of iNOS expression in Big Blue, suggesting the formation of potentially genotoxic nitrogen species. However, crocidolite exposure in separated or mixed cocultures induced no mutagenic effects whereas an increase in Big Blue mutants was detected after exposure to zymosan in mixed cocultures. NR8383 activation by crocidolite is probably insufficient to induce in vitro mutagenic events. The mutagenesis assay based on the coculture of NR8383 and Big Blue cannot be used as an alternative in vitro method to assess the mutagenic properties of asbestos fibres

The site of Montlleó in the context of the Mediterranean and Pyrenean Solutrean

International audienc

Genotoxicity of synthetic amorphous silica nanoparticles in rats following short-term exposure, part 2: Intratracheal instillation and intravenous injection

International audienceSynthetic amorphous silica nanomaterials (SAS) are extensively used in food and tire industries. In many industrial processes, SAS may become aerosolized and lead to occupational exposure of workers through inhalation in particular. However, little is known about the in vivo genotoxicity of these particulate materials. To gain insight into the toxicological properties of four SAS (NM-200, NM-201, NM-202, and NM-203), rats are treated with three consecutive intratracheal instillations of 3, 6, or 12 mg/kg of SAS at 48, 24, and 3 hrs prior to tissue collection (cumulative doses of 9, 18, and 36 mg/kg). Deoxyribonucleic acid (DNA) damage was assessed using erythrocyte micronucleus test and the standard and Fpg-modified comet assays on cells from bronchoalveolar lavage fluid (BALF), lung, blood, spleen, liver, bone marrow, and kidney. Although all of the SAS caused increased dose-dependent changes in lung inflammation as demonstrated by BALF neutrophilia, they did not induce any significant DNA damage. As the amount of SAS reaching the blood stream and subsequently the internal organs is probably to be low following intratracheal instillation, an additional experiment was performed with NM-203. Rats received three consecutive intravenous injections of 5, 10, or 20 mg/kg of SAS at 48, 24, and 3 hrs prior to tissue collection. Despite the hepatotoxicity, thrombocytopenia, and even animal death induced by this nanomaterial, no significant increase in DNA damage or micronucleus frequency was observed in SAS-exposed animals. It was concluded that under experimental conditions, SAS induced obvious toxic effects but did cause any genotoxicity following intratracheal instillation and intravenous injection