Genotoxic and stress inductive potential of cadmium in Xenopus laevis larvae

The present investigation evaluates the toxic potential of Cd in larvae of the frog Xenopus laevis after 12 days of exposure to environmentally relevant contamination levels, close to those measured in the river Lot (France). Several genotoxic and detoxification mechanisms were analyzed in the larvae: clastogenic and/or aneugenic effects in the circulating blood by micronucleus (MN) induction, metallothionein (MT) production in whole larvae, gene analyses and Cd content in the liver and also in the whole larvae. The results show: (i) micronucleus induction at environmental levels of Cd contamination (2, 10, 30 μg L−1); (ii) an increased and concentration-dependent quantity of MT in the whole organism after contamination with 10 and 30 μg Cd L−1 (a three- and six-fold increase, respectively) although no significant difference was observed after contamination with 2 μg Cd L−1; (iii) Cd uptake by the whole organism and by the liver as a response to Cd exposure conditions; (4) up-regulation of the genes involved in detoxification processes and response to oxidative stress, while genes involved in DNA repair and apoptosis were repressed. The results confirm the relevance of the amphibian model and highlight the complementarity between a marker of genotoxicity, MT production, bioaccumulation and genetic analysis in the evaluation of the ecotoxicological impact

Histoire des basques ou Escualdunais primitifs : restaurée d'après la langue les caractères ethnologiques et les moeurs des basques actuels

Digitalización. Vitoria-Gasteiz : Archivos y Bibliotecas, Abril 1994Rústic

A New Thermosensitive smc-3 Allele Reveals Involvement of Cohesin in Homologous Recombination in C. elegans

The cohesin complex is required for the cohesion of sister chromatids and for correct segregation during mitosis and meiosis. Crossover recombination, together with cohesion, is essential for the disjunction of homologous chromosomes during the first meiotic division. Cohesin has been implicated in facilitating recombinational repair of DNA lesions via the sister chromatid. Here, we made use of a new temperature-sensitive mutation in the Caenorhabditis elegans SMC-3 protein to study the role of cohesin in the repair of DNA double-strand breaks (DSBs) and hence in meiotic crossing over. We report that attenuation of cohesin was associated with extensive SPO-11–dependent chromosome fragmentation, which is representative of unrepaired DSBs. We also found that attenuated cohesin likely increased the number of DSBs and eliminated the need of MRE-11 and RAD-50 for DSB formation in C. elegans, which suggests a role for the MRN complex in making cohesin-loaded chromatin susceptible to meiotic DSBs. Notably, in spite of largely intact sister chromatid cohesion, backup DSB repair via the sister chromatid was mostly impaired. We also found that weakened cohesins affected mitotic repair of DSBs by homologous recombination, whereas NHEJ repair was not affected. Our data suggest that recombinational DNA repair makes higher demands on cohesins than does chromosome segregation

Release of CHK-2 from PPM-1.D anchorage schedules meiotic entry

Transition from the stem/progenitor cell fate to meiosis is mediated by several redundant posttranscriptional regulatory pathways i

Inhibition of Cell Growth and Cellular Protein, DNA and RNA Synthesis in Human Hepatoma (HepG2) Cells by Ethanol Extract of Abnormal Savda Munziq of Traditional Uighur Medicine

Abnormal Savda Munziq (ASMq) is a traditional Uighur medicinal herbal preparation, commonly used for the treatment and prevention of cancer. We tested the effects of ethanol extract of ASMq on cultured human hepatoma cells (HepG2) to explore the mechanism of its putative anticancer properties, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) bromide, neutral red and lactate dehydrogenase (LDH) leakage assays, testing the incorporation of 3[H]-leucine and 3[H]-nucleosides into protein, DNA and RNA, and quantifying the formation of malondialdehyde-thiobarbituric acid (MDA) adducts. ASMq ethanol extract significantly inhibited the growth of HepG2 and cell viability, increased the leakage of LDH after 48 hours or 72 hours treatment, in a concentration- and time-dependent manner (P < .05). Cellular protein, DNA and RNA synthesis were inhibited in a concentration- and time-dependent manner (P < .05). No significant MDA release in culture medium and no lipid peroxidation in cells were observed. The results suggest that the cytotoxic effects of ASMq ethanol extract might be related to inhibition of cancer cell growth, alteration of cell membrane integrity and inhibition of cellular protein, DNA and RNA synthesis

Molecular Impacts of Dietary Exposure to Nanoplastics Combined or Not with Arsenic in the Caribbean Mangrove Oysters (Isognomon alatus)

Nanoplastics (NPs) are anthropogenic contaminants that raise concern, as they cross biological barriers. Metals’ adsorption on NPs’ surface also carries ecotoxicological risks to aquatic organisms. This study focuses on the impacts of three distinct NPs on the Caribbean oyster Isognomon alatus through dietary exposure. As such, marine microalgae Tisochrysis lutea were exposed to environmentally weathered mixed NPs from Guadeloupe (NPG), crushed pristine polystyrene nanoparticles (PSC), and carboxylated polystyrene nanoparticles of latex (PSL). Oysters were fed with NP-T. lutea at 10 and 100 µg L−1, concentrations considered environmentally relevant, combined or not with 1 mg L−1 pentoxide arsenic (As) in water. We investigated key gene expression in I. alatus’ gills and visceral mass. NP treatments revealed significant induction of cat and sod1 in gills and gapdh and sod1 in visceral mass. As treatment significantly induced sod1 expression in gills, but once combined with any of the NPs at both concentrations, basal mRNA levels were observed. Similarly, PSL treatment at 100 µg L−1 that significantly induced cat expression in gills or sod1 in visceral mass showed repressed mRNA levels when combined with As (reduction of 2222% and 34%, respectively, compared to the control). This study suggested a protective effect of the interaction between NPs and As, possibly by decreasing both contaminants’ surface reactivity

Stretch-Activated Piezo1 Channel in Endothelial Cells Relaxes Mouse Intrapulmonary Arteries

In intrapulmonary artery (IPA), endothelial cells (EC) respond to mechanical stimuli by releasing vasoactive factors to set the vascular tone. Piezo1, a stretch-activated calcium permeable channel is a sensor of mechanical stress in EC. The present study was undertaken to investigate the implication of Piezo1 in the endothelium-dependent regulation of IPA tone and its potential involvement in pulmonary hypertension, the main disease of this circulation. IPA tone was quantified by means of a myograph in control Piezo1+/+ mouse and in mouse lacking endothelial Piezo1 (EC-Piezo1-/-). Endothelial intracellular calcium concentration ([Ca2+]i) and nitric oxide (NO) production were measured, in mouse or human EC, with fluo-4 and DAF-fm probes, respectively. Immunofluorescence labeling and patch-clamp experiments revealed the presence of Piezo1 channels in EC. Yoda1, a Piezo1 agonist, induced an endothelium-dependent relaxation that was significantly reduced in pulmonary arteries in EC-Piezo1-/- compared to Piezo1+/+ mouse. Yoda1 as well as mechanical stimulation (by osmotic stress) increased [Ca2+]i in mouse or human EC. Consequently, both stimuli increased the production of NO. NO and [Ca2+]i increases were reduced in EC from Piezo1-/- mouse or in the presence of Piezo1 inhibitors. Furthermore, deletion of Piezo1 increased alpha-adrenergic mediated contraction. Finally, in chronically hypoxic mice, a model of pulmonary hypertension, Piezo1 still mediated arterial relaxation and deletion of this channel did not impair the development of the disease. The present study thus demonstrates that endothelial Piezo1 contributes to intrapulmonary vascular relaxation by controlling endothelial [Ca2+]i and NO production and that this effect is still present in pulmonary hypertension

Metallothionein gene identification and expression in the cockle ( Cerastoderma edule) under parasitism (trematodes) and cadmium contaminations

Parmi les organismes benthiques, les bivalves sont souvent utilisés comme bioindicateurs des pollutions environnementales, du fait de leur importante capacité de bioaccumulation des métaux lourds conduisant à l'induction des métallothionéines (MT). Les MT sont de petites protéines cytosoliques capables de fixer les métaux et qui sont impliquées dans l'homéostasie et la détoxication de ces métaux chez les organismes. Ces protéines peuvent être induites par un grand nombre de facteurs tels que les hormones, les stress physiques, le parasitisme. La quantification des MT en relation avec le parasitisme est rarement reportée dans la littérature, bien que le parasitisme soit omniprésent et très délétère chez les bivalves. De plus, seulement un petit nombre de gènes de MT ont été identifiés chez les mollusques. Cette étude décrit la caractérisation de la séquence partielle d'un gène de MT (Cemt1) chez la coque Cerastoderma edule, qui présente plus de 80 % d'homologie avec de nombreuses séquences de MT de bivalves. A partir de cette séquence, des amorces spécifiques, utilisables en PCR quantitative en temps réel, ont été déterminées. Le niveau d'expression du gène Cemt1, ainsi que la quantité de protéine MT ont été analysés chez des individus soumis à différents paramètres : sans parasites ou infestés par le trématode digène Himasthla elongata, et lors d'expositions au cadmium à 15 µg Cd L−1. Des résultats concordants ont été obtenus lors de la quantification des protéines MT et de l'analyse de l'expression du gène Cemt1. Ceux-ci mettent en évidence que les concentrations en MT augmentent significativement par les deux types de traitement (infestation parasitaire et exposition au cadmium).Among benthic organisms, bivalves are often used as bioindicators of environmental pollution because of their high bioaccumulation capacities for heavy metals leading to metallothioneins (MT) induction. MT are small cytosolic metal-binding proteins involved in metal homeostasis and detoxification in living organisms. These proteins can also be induced by a wide range of factors, such as hormones, physical stress, parasitism. MT quantification in relation to parasitism is rarely reported in literature, while parasites are omnipresent and have deleterious impacts on bivalves. Moreover, only a few number of MT genes have been characterized in molluscs. This study describes the partial sequence of the MT gene (Cemt1) in the edible cockle Cerastoderma edule. The cockle's MT cDNA was sequenced and showed over 80% homology to several other bivalve MT sequences. This sequence was then used to determine MT specific primers which can be used in quantitative real time PCR. MT protein and gene expression levels were quantified for individuals selected under different conditions: free from or infected by the digenean trematode Himasthla elongata, and under cadmium exposure at 15 mu g Cd L-1. Results evidenced that MT concentrations were significantly increased by both treatments; parasite infection and Cd exposure. Moreover, congruent results between MT protein and gene expression levels were obtained