HAL du Programme national de recherche environnement-santé-travail (PNR EST)
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PID1 is associated to a respiratory endotype related to occupational exposures to irritants
No full textInternational audienceBackground: Studying associations between genes and asthma endotypes and interactions with environment could help to identify new susceptibility genes. We used a previously identified asthma endotype characterized by adult-onset asthma, poor lung function, and high level of Fluorescent oxidation products, a marker of damages due to oxidative stress. This endotype was associated with high occupational exposure to irritants. We aimed to investigate the associations between genes related to oxidative stress and this endotype, and if the associations differed according to irritants exposure. Methods: We conducted association analyses between the asthma endotype and genetic variants (4715 SNPs) located in 422 genes involved in the “response to oxidative stress” in adults from the Epidemiological study on the Genetic and Environment of Asthma. Analyses using logistic regression were conducted first in all participants, and then separately among high vs. non-exposed participants to assess whether association differs according to irritants exposure. Results: An association was found between the SNP rs1419958 located in PID1 gene and the endotype (P = 2.2E-05), reaching significance level after correction for multiple testing. This association was even more significant in non-exposed participants (P = 1.06E-06) while there was no association in participants with high exposure to occupational irritants. Conclusion: This study showed a significant association between an asthma endotype and PID1, a promising candidate gene, the association being different according to the exposure to irritants. These results highlight the interest of studying asthma endotypes in association with genes from candidate pathways and their link with occupational irritants to decipher asthma etiology
Stable isotopes of a terrestrial amphibian illustrate fertilizer-related nitrogen enrichment of food webs in agricultural habitats
No full textInternational audienceTo comprehensively assess the impacts of agricultural practices on biodiversity in complex landscapes mixingboth agricultural habitats and remnants of other (presumably more favorable) types of habitats, a prerequisite isto evaluate to which extent agricultural habitats are actually used by a given species. Here, we tested whether the stable isotope method can help to discriminate habitat use of a wild vertebrate, the spined toad (Bufo spinosus). We expected habitat to influence their δ13C values and the use of fertilizers to increase δ15N values of individuals from agricultural landscapes. Based on 114 toads from seven sites characterized by contrasted habitats (agricultural, forest or mixed habitats), we found that toad blood δ15N values were positively related to agricultural surface area, a result that was corroborated by diverging blood δ15N values between habitat categories. Conversely, toad δ13C values did not vary according to the habitat. Our results suggest that isotopic values (especially δ15N) could be a powerful tool to assess agricultural habitat use in terrestrial taxa. Further studies should usefully investigate whether individual δ15N values can be used as a fingerprint of other constraints of agricultural habitats (e.g., contaminants) in agricultural landscapes
In situ exposure to glyphosate induces tolerance acquisition by phototrophic biofilms: the case study of the Cleurie river (France, Vosges mountains)
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The Benzene Hematotoxic and Reactive Metabolite 1,4-Benzoquinone Impairs the Activity of the Histone Methyltransferase SET Domain Containing 2 (SETD2) and Causes Aberrant Histone H3 Lysine 36 Trimethylation (H3K36me3)
No full textInternational audienceHuman SETD2 is the unique histone methyltransferase that generates H3K36 trimethylation (H3K36me3), an epigenetic mark that plays a key role in normal hematopoiesis. Interestingly, recurrent inactivating mutations of SETD2 and aberrant H3K36me3 are increasingly reported to be involved in hematopoietic malignancies. Benzene (BZ) is a ubiquitous environmental pollutant and carcinogen that causes leukemia. The leukemogenic properties of BZ depend on its biotransformation in the bone marrow into oxidative metabolites, in particular 1,4-benzoquinone (BQ). This hematotoxic metabolite can form DNA and protein adducts that result in the damage and the alteration of cellular processes. Recent studies suggest that BZ-dependent leukemogenesis could depend on epigenetic perturbations, notably aberrant histone methylation. We investigated whether H3K36 trimethylation by SETD2 could be impacted by BZ and its hematotoxic metabolites. Herein, we show that BQ, the major leukemogenic metabolite of BZ, inhibits irreversibly the human histone methyltransferase SETD2, resulting in decreased H3K36me3. Our mechanistic studies further indicate that the BQ-dependent inactivation of SETD2 is due to covalent binding of BQ to reactive Zn-finger cysteines within the catalytic domain of the enzyme. The formation of these quinoprotein adducts results in loss of enzyme activity and protein crosslinks/oligomers. Experiments conducted in hematopoietic cells confirm that exposure to BQ results in the formation of SETD2 crosslinks/oligomers and concomitant loss of H3K36me3 in cells. Taken together, our data indicate that BQ, a major hematotoxic metabolite of BZ, could contribute to BZ-dependent leukemogenesis by perturbing the functions of SETD2, a histone lysine methyltransferase of hematopoietic relevance
Antenna/Human Body Coupling in 5G Millimeter-Wave Bands: Do Age and Clothing Matter?
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Ontogenetic changes in activity, locomotion and behavioural complexity in tadpoles
No full textInternational audienceMetamorphosis is a widespread developmental process that involves considerable changes in morphology, habitatuse, ecology and behaviour between early developmental (larval) stages and adult forms. Among amphibians,anuran larvae (tadpoles) undergo massive morphological and ecological changes during their development, withearly stages characterized by somatic growth, whereas more conspicuous changes (i.e. metamorphosis) occur laterduring development. In this study, we examined how locomotor and behavioural traits covary with morphology (bodysize) and metamorphosis (hindlimb and forelimb development) across developmental stages in spined toad (Bufospinosus) tadpoles. As expected, we found that locomotion and behaviour undergo significant changes during tadpoledevelopment. These changes are curvilinear across developmental stages, with a phase of increasing activity andlocomotion followed by a phase of stasis and/or reduction in locomotion and behavioural complexity. All the metricswe investigated indicate that the peak of activity and associated behaviour is situated at a pivotal stage whensomatic growth decreases and significant morphological changes occur (i.e. hindlimb growth). Future studies thataim to investigate determinants of locomotion should include developmental stages as covariates in order to assesswhether the sensitivity of locomotion to environmental variables changes across developmental stages
An overview of the literature on emerging pollutants: Chlorinated derivatives of Bisphenol A (ClxBPA)
No full textInternational audienceContext: Bisphenol A (BPA) is a ubiquitous contaminant with endocrine-disrupting effects in mammals. During chlorination treatment of drinking water, aqueous BPA can react with chlorine to form chlorinated derivatives of BPA (mono, di, tri and tetra-chlorinated derivatives) or ClxBPA.Objective: The aim of this study is to summarize and present the state of knowledge on human toxicological risk assessment of ClxBPA.Materials and methods: A search on ClxBPA in the PubMed database was performed based on studies published between 2002 and 2021. Forty-nine studies on chlorinated derivatives of BPA were found. Available information on their sources and levels of exposure, their effects, their possible mechanisms of action and their toxicokinetics data was extracted and presented.Results: ClxBPA have been essentially detected in environmental aqueous media. There is evidence in toxicological and epidemiological studies that ClxBPA also have endocrine-disrupting capabilities. These emerging pollutants have been found in human urine, serum, breast milk, adipose and placental tissue and can constitute a risk to human health. However, in vitro and in vivo toxicokinetic data on ClxBPA are scarce and do not allow characterization of the disposition kinetics of these compounds.Conclusion: More research to assess their health risks, specifically in vulnerable populations, is needed. Some water chlorination processes are particularly hazardous, and it is important to evaluate their chlorination by-products from a public health perspective
Microbiological Contamination of the Office Environment in Dental and Medical Practice
No full textInternational audienceThe microbiological contamination of the environment in independent healthcare facilities such as dental and general practitioner offices was poorly studied. The aims of this study were to describe qualitatively and quantitatively the bacterial and fungal contamination in these healthcare facilities and to analyze the antibiotic resistance of bacterial pathogens identified. Microbiological samples were taken from the surfaces of waiting, consulting, and sterilization rooms and from the air of waiting room of ten dental and general practitioner offices. Six surface samples were collected in each sampled room using agar contact plates and swabs. Indoor air samples were collected in waiting rooms using a single-stage impactor. Bacteria and fungi were cultured, then counted and identified. Antibiograms were performed to test the antibiotic susceptibility of bacterial pathogens. On the surfaces, median concentrations of bacteria and fungi were 126 (range: 0–1280) and 26 (range: 0–188) CFU/100 cm2, respectively. In indoor air, those concentrations were 403 (range: 118–732) and 327 (range: 32–806) CFU/m3, respectively. The main micro-organisms identified were Gram-positive cocci and filamentous fungi, including six ubiquitous genera: Micrococcus, Staphylococcus, Cladosporium, Penicillium, Aspergillus, and Alternaria. Some antibiotic-resistant bacteria were identified in general practitioner offices (penicillin- and erythromycin-resistant Staphylococcus aureus), but none in dental offices. The dental and general practitioner offices present a poor microbiological contamination with rare pathogenic micro-organisms
Psychosocial work exposures and health outcomes: a meta-review of 72 literature reviews with meta-analysis
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Prenatal exposure to a wide range of environmental chemicals and child behaviour between 3 and 7 years of age – An exposome-based approach in 5 European cohorts
No full textInternational audienceBackground: Studies looking at associations between environmental chemicals and child behaviour usually consider only one exposure or family of exposures.Objective: This study explores associations between prenatal exposure to a wide range of environmental chemicals and child behaviour.Methods: We studied 708 mother-child pairs from five European cohorts recruited in 2003–2009. We assessed 47 exposure biomarkers from eight chemical exposure families in maternal blood or urine collected during pregnancy. We used the Strengths and Difficulties Questionnaire (SDQ) to evaluate child behaviour between three and seven years of age. We assessed associations of SDQ scores with exposures using an adjusted least absolute shrinkage and selection operator (LASSO) considering all exposures simultaneously and an adjusted exposome-wide association study (ExWAS) considering each exposure independently.Results: LASSO selected only copper (Cu) as associated with externalizing behaviour. In the ExWAS, bisphenol A [BPA, incidence rate ratio (IRR): 1.06, 95% confidence interval (95%CI): 1.01;1.12] and mono-n-butyl phthalate (MnBP, IRR: 1.06, 95%CI: 1.00;1.13) were associated with greater risk of externalizing behaviour problems. Cu (IRR: 0.90, 95%CI: 0.82;0.98), perfluoroundecanoate (PFUnDA, IRR: 0.92, 95%CI: 0.84;0.99) and organochlorine compounds (OCs) were associated with lower risk of externalizing behaviour problems, however the associations with OCs were mainly seen among women with insufficient weight gain during pregnancy. Internalizing score worsen in association with exposure to diethyl thiophosphate (DETP, IRR: 1.11, 95%CI: 1.00;1.24) but the effect was driven by the smallest cohort. Internalizing score improved with increased concentration of perfluorooctane sulfonate (PFOS, IRR: 0.92, 95%CI: 0.85;1.00), however the association was driven by the two smallest cohorts with the lowest PFOS concentrations.Discussion: This study added evidence on deleterious effects of prenatal exposure to BPA and MnBP on child behaviour. Other associations should be interpreted cautiously since they were not consistent with previous studies or they have not been studied extensively