Éditeur(s) : Université des Antilles AREBio Groupe de recherche BIOSPHERES : BIOlogie, Sciences Physiques & Humaines pour les énergies Renouvelables, l
Extrait de : 1er colloque international BIOSPHERES, du 18 au 20 juin 2019. Université des Antilles
Description : The Chemical Purification, analysis and Screening core laboratories (CPAS) are located at the University of South Florida campus in Tampa. This core offers instrumentation and expertise in fractionation, purification, and various chemical analyses to support synthetic and natural products drug discovery research groups. Our main equipment are dedicated to chromatographic separation and purification (MPLC, HPLC) and mass-spectrometry for analytic detection, quantification and identification (LC-MS SQ, QqQ and QToF). The CPAS services also include Circular Dichroism spectrometry, general spectroscopic characterization (UV, FTIR), lyophilization (bench top and high capacity freeze-dryers), synthesis (microwave reactor), ADME screening (permeability and drug solubility testing), and high-throughput screening development capability (automated liquid handler and multimode plate reader). An example of three significant studies will be presented at the conference to illustrate the CPAS core facility services: 1) Identification of new bioactive compounds from mangrove endophytic fungi as potential alternatives to malaria drug resistance, 2) Myricanol isolated from Bayberry (Myrica Cerifera) and its synthetic derivatives targeting the microtubuleassociated protein tau accumulation in the Alzheimer's disease and 3) New ent-labdane diterpenes with solid tumor cell lines antiproliferative properties from the endemic plant Eupatorium obtusissmum from the island of Hispaniola. The core provides research lab training workshops in advanced technology and assistance so users can operate any instruments available in the laboratories to successfully accomplish their analyses and research projects.

Droits : CC-BY-NC-ND - Attribution - Pas d'utilisation commerciale - Pas de modification
Permalien : http://www.manioc.org/fichiers/V19063
V19063

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The aim of this study was to establish a new QuEChERS (quick, easy, cheap, effective, rugged and safe) method coupled to gas chromatography-mass spectrometry (GC-MS) detection for the evaluation of the pesticide biodistribution in specific maternal and fetal tissues. This method was validated for the quantification of pesticides such as chlorotriazines (atrazine, simazine and propazine), their chlorinated metabolites (DIA, DEA and DACT). This new QuEChERS method was developed to facilitate extraction from small tissues such as fetal tissues (mean value: 200mg). The limits of detection, quantification, recovery, precision and accuracy were evaluated for different tissues (liver and brain) and blood. LOD and LOQ ranged between 0.34 and 3.27 ng/g and 1.04 to 9.91 ng/g, respectively. Recovery exceeded 80% for all pesticides, except DACT, with an associated RSD<15%. Precision and accuracy satisfied the criteria usually applied in the validation of bioanalytical methods. The results obtained indicate that this technique is suitable for use in studies of the biodistribution of pesticides in fetal tissues and can be used to evaluate the risk of exposure to pesticides during gestation.
ISSN: 0731-7085

hal-01122837
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122837
PUBMED : 25497890
DOI : 10.1016/j.jpba.2014.10.035

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
People are exposed to multiple pollutants, especially indoors, in particular through ingestion of indoor settled dust. In the perspective of a cumulative risk assessment, a multi-residue analytical method based on pressurized liquid extraction (PLE) and gas chromatography/tandem mass spectrometry (GC/MS/MS) was developed for the simultaneous analysis in indoor dust of several classes of semi-volatile organic compounds (SVOCs) of health concern, from trace to highly concentrated compounds, including musk fragrances, organochlorines (OCs), organophosphates (OPs), polycyclic aromatic hydrocarbons (PAHs), polybromodiphenylethers (PBDEs), polychlorobiphenyls (PCBs), phthalates and pyrethroids. The method was validated in terms of limits of quantification (LOQ), and accuracy and precision via spiking experiments on an inert material (Celite(®) 545) and replicate analysis of the standard reference material SRM 2585 supplied by the National Institute of Standards and Technology (NIST). Method LOQs for 200 mg samples of sieved dust were 26 ng g(-1) for PCBs and some OCs, 65 ng g(-1) for musks, OPs, PAHs, PBDEs, pyrethroids, other OCs and some phthalates, 132 ng g(-1) for butylbenzylphthalate (BBP), 197 ng g(-1) for tributylphosphate and 1579 ng g(-1) for other phthalates. Quadratic calibration curves were established for each compound by analyzing at least five calibration solutions and exhibited determination coefficients higher than 0.999. The method was successfully applied to the SRM 2585 and seven real indoor dust samples. The results obtained on SRM 2585 demonstrate both excellent reproducibility and agreement with the indicative, reference or certified values and provide, for the first time, indicative concentrations for chlorpyrifos, diazinon, diisononylphthalate (DiNP) and tetramethrin. The results obtained on real dust samples illustrate the ability of the proposed method to quantify a wide range of SVOCs in a single analysis, making it appropriate for environmental monitoring programs or large-scale studies with a large number of samples.
ISSN: 0021-9673

hal-00994493
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00994493
DOI : 10.1016/j.chroma.2014.02.004
PUBMED : 24598454

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Meconium is the first fecal excretion of newborns. This complex accumulative matrix allows assessing the exposure of the fetus to xenobiotics during the last 6 months of pregnancy. To determine the eventual effect of fetal exposure to micropollutants in this matrix, robust and sensitive analytical methods must be developed. This article describes the method development of liquid chromatography methods coupled to triple quadrupole mass spectrometry for relevant pollutants. The 28 selected target compounds had different physico-chemical properties from very polar (glyphosate) to non-polar molecules (pyrethroids). Tests were performed with three different types of columns: reversed phase, ion exchange and HILIC. As a unique method could not be determined for the simultaneous analysis of all compounds, three columns were selected and suitable chromatographic methods were optimized. Similar results were noticed for the separation of the target compounds dissolved in either meconium extract or solvent for reversed phase and ion exchange columns. However, for HILIC, the matrix had a significant influence on the peak shape and robustness of the method. Finally, the analytical methods were applied to “real” meconium samples.
ISSN: 0039-9140

hal-01141722
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01141722
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01141722/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01141722/file/Development%20of%20liquid%20chromatography%20%281%29.pdf
PUBMED : 25863396

Éditeur(s) : Mdpi Ag
Résumé : Marine pelagic diazotrophic cyanobacteria of the genus Trichodesmium (Oscillatoriales) are widespread throughout the tropics and subtropics, and are particularly common in the waters of New Caledonia. Blooms of Trichodesmium are suspected to be a potential source of toxins in the ciguatera food chain and were previously reported to contain several types of paralyzing toxins. The toxicity of water-soluble extracts of Trichodesmium spp. were analyzed by mouse bioassay and Neuroblastoma assay and their toxic compounds characterized using liquid chromatography coupled with tandem mass spectrometry techniques. Here, we report the first identification of palytoxin and one of its derivatives, 42-hydroxy-palytoxin, in field samples of Trichodesmium collected in the New Caledonian lagoon. The possible role played by Trichodesmium blooms in the development of clupeotoxism, this human intoxication following the ingestion of plankton-eating fish and classically associated with Ostreopsis blooms, is also discussed.
Marine Drugs (1660-3397) (Mdpi Ag), 2011-04 , Vol. 9 , N. 4 , P. 543-560

Droits : 2011 MDPI Publishing
http://archimer.ifremer.fr/doc/00040/15143/12576.pdf
DOI:10.3390/md9040543
http://archimer.ifremer.fr/doc/00040/15143/

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The 90-kDa heat shock protein (Hsp90) is a highly flexible dimer able to self-associate in the presence of divalent cations or under heat shock. In a previous work, we focused on the Mg2 +-induced oligomerization process of Hsp90, and characterized the oligomers. Combining analytical ultracentrifugation, size-exclusion chromatography coupled to multi-angle laser light scattering and high-mass matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we studied the interaction of p23 with both Hsp90 dimer and oligomers. Even if p23 predominantly binds the Hsp90 dimer, we demonstrated, for the first time, that p23 is also able to interact with Hsp90 oligomers, shifting the Hsp90 dimer-oligomers equilibrium toward dimer. Our results showed that the Hsp90:p23 binding stoichiometry decreases with the Hsp90 oligomerization degree. Therefore, we propose a model in which p23 would act as a “protein wedge” regarding the Hsp90 dimer closure and the Hsp90 oligomerization process
ISSN: 1570-9639

hal-01174219
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01174219
DOI : 10.1016/j.bbapap.2015.07.003
PUBMED : 26151834

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
This work relates to the characterisation of the predominant gill protein of the white clam, Codakia orbicularis (Linné, 1758), which harbours endosymbiotic sulphur-oxidising chemoautotrophic bacteria. Total RNA was extracted from the clam to perform 3'rapid amplification of cDNA ends (3'RACE) using degenerate oligonucleotides prepared from a partial sequence of a predominant protein of about 14kDa, termed codakine. The partial peptide sequence was obtained by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and Edman degradation. Clones isolated from the cDNA library and containing the gene of interest were used in polymerase chain reaction (PCR). The PCR and RACE-PCR products were sequenced to determine the entire coding DNA sequence of codakine. BLAST analysis revealed about 23% to 29% sequence identity between codakine and various animal C-type lectins that are often involved in symbiosis and immune defences. Codakine also contains the motifs and domains of Ca(2+)-dependent C-type lectins, and in particular the tripeptide EPN motif frequently found in mannose-binding lectins (MBLs). Analysis of the protein by affinity chromatography on a mannose-agarose column is consistent with the findings that codakine is a dimeric Ca(2+)-dependent MBL of about 29kDa. Based on the present results, it is hypothesised that this novel C. orbicularis gill protein is involved in the recognition of symbiotic and pathogenic bacteria.
ISSN: 1050-4648

hal-00746015
https://hal.univ-antilles.fr/hal-00746015
DOI : 10.1016/j.fsi.2006.06.013
PUBMED : 17169576

Éditeur(s) : Gauthier-Villars
Résumé : Mud fields located In the inner part of shelves in front of large estuaries are preferential environments for the investigation of the mechanisms and evolution in time of the supply of such sedimentary bodies. The study of different constituents of the particulate organic matter trapped in the sediments of the West Gironde mud patch contributes to the knowledge of the input origins. This study was carried out with different techniques, including pyrolysis-gas chromatography-mass spectrometry and high performance liquid chromatography, on samples from a core collected in the centre of the mud field. At the bottom of the core, the increase of sugars, amino-sugars and some aromatic hydrocarbons may indicate a more marine character of organic components. The same appears to be the case at the top of the core, where, despite a finer sedimentation, biochemical characteristics could show a more pronounced marine influence than in the middle part. In the middle part of the core, on the other hand, the increase in phenols could result from an increase in lignin-derived. terrestrial inputs. The increase in pyrolysis-derived cyclopentenone may indicate the same terrestrial influence, because this component has its origin in aliphatic polycarboxylic acids resulting from sail leaching. The continental character of the sedimentation is also reflected in the increase of the silt-clay fractions representative of suspended matter originating in the Gironde estuary, associated with a slight carbonate decrease. The taxonomic significance of some phenols is noteworthy: this is especially the case of the cinnamyls which, in the middle part of the core, emphasize the input of herbaceous debris and of the hydroxybenzyls which, at the bottom, provide evidence of the algal origin of part of the organic material. Thus, by means of pyrolysis results and HPLC phenol analysis, it is possible to establish the more or less continental signature of organic components trapped in the ''Ouest-Gironde'' mud patch. This study of organic matter, which confirms earlier sedimentological and micropaleontological data, constitutes a new approach, adapted to the identification of the origin of carbon sources.
Oceanolica Acta (0399-1784) (Gauthier-Villars), 1997 , Vol. 20 , N. 5 , P. 687-695

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/00093/20426/18093.pdf
http://archimer.ifremer.fr/doc/00093/20426/

Éditeur(s) : HAL CCSD Wiley-Blackwell
Résumé : International audience
Heterocyclic aromatic amines (HAA) are formed in cooked meat, poultry and fish but also arise in tobacco smoke and exhaust gases. HAA are potential human carcinogens, which require metabolic activation to exert their genotoxicity. Human tissues can bioactivate HAA to produce reactive intermediates that bind to DNA. HAA DNA adduct formation occurs in human hepatocytes; however, the potential of HAA to form DNA adducts has not been investigated in human T lymphocytes. In this study, we investigated the ability of human T lymphocytes activated with PMA/Ionomycin or CD3/CD28 to express functional CYP1 activity and bioactivate three major HAA: 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-9H-pyrido[2,3-b]indole (AαC) to form DNA adducts. Adducts were measured by ultraperformance liquid chromatography-electrospray ionization/multistage scan mass spectrometry. The highest level of DNA adducts occurred for AαC (16 adducts per 109 nucleotides), followed by PhIP (9 adducts per 109 nucleotides). In contrast, DNA adducts formed from MeIQx and the structurally related aromatic amine 4-aminobiphenyl, a known human carcinogen, were below the limit of detection (< 3 adducts per 109 nucleotides). Moreover, we demonstrate that AαC is a potent inducer of CYP1A1 and CYP1B1 activity through a transcriptional mechanism involving the AhR pathway. Overall, our results highlight the capacity of activated human T lymphocytes to more efficiently bioactivate AαC to form DNA adducts than other prominent HAA or 4-ABP. Environ. Mol. Mutagen. 57:656-667, 2016.
ISSN: 0893-6692

hal-01400486
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01400486
DOI : 10.1002/em.22059
PUBMED : 27801952

Éditeur(s) : HAL CCSD Springer Verlag (Germany)
Résumé : International audience
A hybrid linear ion-trap Fourier-transform ion cyclotron resonance mass spectrometer was used for top-down characterization of the abundant human salivary Cystatins, including S, S1, S2, SA, SN, C, and D, using collisionally activated dissociation (CAD) after chromatographic purification of the native, disulfide intact proteins from saliva. Post-translational modifications and protein sequence polymorphisms arising from single nucleotide polymorphisms (SNPs) were assigned from precursor and product ion masses at a tolerance of 10 ppm allowing confident identification of individual intact mass tags. Cystatins S, S1, S2, SA and SN were cleaved of a N-terminal 20 amino-acid signal peptide, and Cystatin C a 26-residue peptide, to yield a generally conserved N-terminus. In contrast, Cystatin D isoforms with 24 and 28 amino-acid residue N-terminal truncations were found such that their N-termini were not conserved. Cystatin S1 was phosphorylated at Ser3, while S2 was phosphorylated at Ser1 and Ser3 of the mature protein, in agreement with previous work. Both Cystatin D isoforms carried the polymorphism C46R (SNP: rs1799841). The 14328 Da isoform of Cystatin SN previously assigned with polymorphism P31L due to a SNP (rs2070856) was found only in whole saliva. Parotid secretions contained no detectable Cystatins while whole saliva largely mirrored the contents of submandibular/sublingual (SMSL) secretions. Top-down high-resolution mass spectrometry is a powerful tool for the identification and characterization of potential protein biomarkers in saliva.
ISSN: 1044-0305

hal-00677483
https://hal.archives-ouvertes.fr/hal-00677483
DOI : 10.1016/j.jasms.2010.01.025

Éditeur(s) : HAL CCSD National Institute of Environmental Health Sciences
Résumé : International audience
BACKGROUND: Glycol ethers are present in a wide range of occupational and domestic products. Animal studies have suggested that some of them may affect ovarian function. OBJECTIVE: To study the relation between women's exposure to glycol ethers and time to pregnancy. METHODS: Urine from randomly selected women in the PELAGIE mother-child cohort who had samples collected before 19 weeks of gestation was tested to measure eight glycol ether metabolites by chromatography coupled to mass spectrometry. Time to pregnancy was collected at the beginning of the pregnancy by asking women how many months they took to conceive. Associations between metabolite levels and time to pregnancy were estimated in 519 women with complete data using discrete-time Cox proportional hazards models to adjust for potential confounders. RESULTS: Glycol ether metabolites were detected in 6% (for ethoxyacetic acid) to 93% (for phenoxyacetic and butoxyacetic acids) of urine samples. Phenoxyacetic acid was the only metabolite with a statistically significant association with longer time to pregnancy (fecundability OR 0.82; 95% CI: 0.63, 1.06 for the second and third quartile combined; fecundability OR 0.70; 95% CI: 0.52, 0.95 for a fourth-quartile (≥1.38 mg/L) vs. first-quartile concentration (<0.14 mg/L)). This association remained stable after multiple sensitivity analyses. CONCLUSION: Phenoxyacetic acid, which was present in most of the urine samples tested in our study, was associated with increased time to pregnancy. This metabolite and its main parent compound, 2-phenoxyethanol, are plausible causes of decreased fecundability, but may also be surrogates for potential co-exposures frequently present in cosmetics.
ISSN: 0091-6765

hal-00866023
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00866023
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00866023/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00866023/file/Urinary_Glycol_Ether-accepted.pdf
DOI : 10.1289/ehp.1206103

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Fish mucus has important biological and ecologicalroles such as defense against fish pathogens andchemical mediation among several species. A non-targetedliquid chromatography–mass spectrometry metabolomicapproach was developed to study gill mucus of eight butterflyfishspecies in Moorea (French Polynesia), and theinfluence of several fish traits (geographic site and reefhabitat, species taxonomy, phylogeny, diet and parasitismlevels) on the metabolic variability was investigated. Abiphasic extraction yielding two fractions (polar and apolar)was used. Fish diet (obligate corallivorous, facultativecorallivorous or omnivorous) arose as the main driver ofthe metabolic differences in the gill mucus in both fractions,accounting for 23% of the observed metabolic variabilityin the apolar fraction and 13% in the polar fraction.A partial least squares discriminant analysis allowed us toidentify the metabolites (variable important in projection,VIP) driving the differences between fish with differentdiets (obligate corallivores, facultative corallivores andomnivorous). Using accurate mass data and fragmentationdata, we identified some of these VIP as glycerophosphocholines,ceramides and fatty acids. Level of monogeneangill parasites was the second most important factor shapingthe gill mucus metabolome, and it explained 10% of themetabolic variability in the polar fraction and 5% in theapolar fraction. A multiple regression tree revealed that themetabolic variability due to parasitism in the polar fractionwas mainly due to differences between non-parasitized andparasitized fish. Phylogeny and butterflyfish species werefactors contributing significantly to the metabolic variabilityof the apolar fraction (10 and 3%, respectively) buthad a less pronounced effect in the polar fraction. Finally,geographic site and reef habitat of butterflyfish species didnot influence the gill mucus metabolome of butterflyfishes.
ISSN: 0722-4028

hal-01563312
https://hal-univ-perp.archives-ouvertes.fr/hal-01563312
DOI : 10.1007/s00338-017-1554-0

Éditeur(s) : HAL CCSD American Chemical Society
Résumé : International audience
The 90-kDa heat shock protein (Hsp90) is a highly flexible dimer able to self-associate in the presence of divalent cations or under heat shock. This study investigated the relationship between Hsp90 oligomers and the Hsp90 cochaperone Aha1 (activator of Hsp90 ATPase). The interactions of Aha1 with Hsp90 dimers and oligomers were evaluated by ultracentrifugation, size-exclusion chromatography coupled to multiangle laser light scattering and high-mass matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Hsp90 dimer was able to bind up to four Aha1 molecules, and Hsp90 oligomers are also able to interact with Aha1. The binding of Aha1 did not interfere with the Hsp90 oligomerization process. Except for Hsp90 dimer, the stoichiometry of the interaction remained constant, at 2 Aha1 molecules per Hsp90 dimer, regardless of the degree of Hsp90 oligomerization. Moreover, Aha1 predominantly bound to Hsp90 oligomers. Thus, the ability of Hsp90 oligomers to bind the Aha1 ATPase activator reinforces their role within the Hsp90 chaperone machineries
ISSN: 0003-2700

hal-01175535
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01175535
DOI : 10.1021/acs.analchem.5b00051
PUBMED : 26076190

Éditeur(s) : Elsevier
Résumé : In the Gulf of Gabes (Tunisia, Eastern Mediterranean sea), the grooved carpet shell Ruditapes decussatus has been seen to contain persistent levels of gymnodimine (GYM) for several years. The present experimental work represents the first attempt to assess detoxification kinetics of fast-acting toxins (FAT) in marine molluscs fed specific diets of non-toxic algae (Isochrysis galbana). To find an optimal detoxification method, two experiments were performed in which clams were first fed the toxic dinoflagellate Karenia selliformis to artificially contaminate them with GYM, thus simulating the effect of natural toxic episodes. As a second step, the same clams were fed a non-toxic algae, I. galbana. to speed up the detoxification process. Changes in toxin content over the whole experiment were assessed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) analysis. The first results revealed (i) faster detoxification rates in digestive gland (DG) when clams were fed on L galbana compared with a starved control (no food) and (ii) a typical detoxification pattern, i.e. a rapid drop in toxin content within the first days followed by a secondary slower decrease. GYM levels could be reduced approximately to less than 5% within 7-8 days in clams fed I. galbana, according to the initial toxin levels of 1400 and 9400 mu g GYM/kg of DG, respectively. At the end of the second experiment, DSP mouse bioassay was negative when GYM was less than 100 mu g/kg DG. (C) 2009 Elsevier B.V. All rights reserved.
Harmful Algae (1568-9883) (Elsevier), 2010-02 , Vol. 9 , N. 2 , P. 200-207

Droits : 2010 Elsevier Ltd All rights reserved.
http://archimer.ifremer.fr/doc/2010/publication-7488.pdf
DOI:10.1016/j.hal.2009.10.002
http://archimer.ifremer.fr/doc/00000/7488/

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Meconium is the earliest stool of newborns, and is a complex matrix that reflects the degree of exposure of the fetus to xenobiotics. To investigate fetal exposure to volatile organic compounds, an analytical method was developed to identify and quantify BTEX (benzene, toluene, ethylbenzene, and o,m,p-xylene) and two chlorinated solvents (trichloroethylene and tetrachloroethylene) in meconium. Headspace-solid-phase microextraction coupled with gas chromatography-mass spectrometry was selected because it is simple, sensitive, can be automated, and requires no extensive sample preparation. Several extraction variables were optimized (fiber type, incubation time, temperature of fiber, and use of salt). Because meconium is a complex matrix, quantification by SPME was considered carefully because of potential interference, for example competitive adsorption. Calibration in water was compared with calibration in meconium using external and internal methods (with isotope-labeled compounds). In meconium, limits of quantification were determined to be in the range 0.064-0.096 ng g(-1) for the investigated compounds. All target compounds were determined in "real-case" meconium samples.
ISSN: 1618-2642

hal-01064967
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01064967
DOI : 10.1007/s00216-014-7836-2
PUBMED : 24838489

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND: Studies relating long-term exposure to persistent organochlorine pollutants (POPs) with endocrine activities (endocrine disrupting chemicals) on circulating levels of steroid hormones have been limited to a small number of hormones and reported conflicting results. OBJECTIVE: We examined the relationship between serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulphate, androstenedione, androstenediol, testosterone, free and bioavailable testosterone, dihydrotestosterone, estrone, estrone sulphate, estradiol, sex-hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone as a function of level of exposure to three POPs known to interfere with hormone-regulated processes in different way: dichlorodiphenyl dichloroethene (DDE), polychlorinated biphenyl (PCB) congener 153, and chlordecone. METHODS: We collected fasting, morning serum samples from 277 healthy, non obese, middle-aged men from the French West Indies. Steroid hormones were determined by gas chromatography-mass spectrometry, except for dehydroepiandrosterone sulphate, which was determined by immunological assay, as were the concentrations of sex-hormone binding globulin, follicle-stimulating hormone and luteinizing hormone. Associations were assessed by multiple linear regression analysis, controlling for confounding factors, in a backward elimination procedure, in multiple bootstrap samples. RESULTS: DDE exposure was negatively associated to dihydrotestosterone level and positively associated to luteinizing hormone level. PCB 153 was positively associated to androstenedione and estrone levels. No association was found for chlordecone. CONCLUSIONS: These results suggested that the endocrine response pattern, estimated by determining blood levels of steroid hormones, varies depending on the POPs studied, possibly reflecting differences in the modes of action generally attributed to these compounds. It remains to be investigated whether this response pattern is predictive of the subsequent occurrence of disease.
ISSN: 1932-6203

hal-00876025
https://hal.archives-ouvertes.fr/hal-00876025
https://hal.archives-ouvertes.fr/hal-00876025/document
https://hal.archives-ouvertes.fr/hal-00876025/file/Persistent_Organochlorine-accepted.pdf
DOI : 10.1371/journal.pone.0066460

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
: Human exposure to xenobiotics is usually estimated by indirect methods. Biological monitoring has emerged during the last decade to improve assessment of exposure. However, biomonitoring is still an analytical challenge, because the amounts of sample available are often very small yet analysis must be as thorough and sensitive as possible. The purpose of this work was to develop an untargeted "exposomics" approach by using ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS), which was applied to the characterization of pesticide metabolites in urine from pregnant women from a French epidemiological cohort. An upgradable list of pesticides commonly used on different crops, with their metabolites (more than 400 substances) was produced. Raw MS data were then processed to extract signals from these substances. Metabolites were identified by tandem mass spectrometry; putative identifications were validated by comparison with standards and metabolites generated by experiments on animals. Finally, signals of identified compounds were statistically analyzed by use of multivariate methods. This enabled discrimination of exposure groups, defined by indirect methods, on the basis of four metabolites from two fungicides (azoxystrobin, fenpropimorph) used in cereal production. This original approach applied to pesticide exposure can be extended to a variety of contaminant families for upstream evaluation of exposure from food and the environment.
ISSN: 1618-2642

hal-00875889
https://hal.archives-ouvertes.fr/hal-00875889
DOI : 10.1007/s00216-013-7136-2
PUBMED : 23892877

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
People are exposed to multiple pollutants, especially indoors. In the perspective of a cumulative risk assessment, a multi-residue analytical method was developed to assess the contamination of indoor suspended particulate matter by 55 semi-volatile organic compounds (SVOCs) including musk fragrances, organochlorines (OCs), organophosphates (OPs), polycyclic aromatic hydrocarbons (PAHs), polybromodiphenylethers (PBDEs), polychlorobiphenyls (PCBs), phthalates and pyrethroids. It is based on thermal desorption (TD) coupled with gas chromatography/mass spectrometry (GC/MS). Once the thermal desorption conditions were optimized, the method was validated in terms of quantification limits and accuracy using a standard reference material (SRM 2585). Instrumental quantification limits were 10pg (some OCs, some pyrethroids, musk fragrances, OPs, PAHs, PBDEs and PCBs), 100pg (phthalates and other OCs) and 1000pg (other pyrethroids) corresponding respectively to method quantification limits of 1, 10, and 100pg/m(3) for a sampled air volume of 20m(3). Calibration quadratic curves for ranges of 10-1000, 100-10,000, and 1000-100,000pg, depending on the substance, exhibit determination coefficients above 0.999. Recoveries were between 61 and 96% for chlorinated pesticides, PAHs, PBDEs and PCBs present in the SRM 2585. A test of the method on indoor particulate matter samples (PM(10)) collected on quartz fiber filters in French dwellings demonstrated its ability to quantify SVOCs from a small amount of PM.
ISSN: 0021-9673

hal-00732133
https://hal.archives-ouvertes.fr/hal-00732133
DOI : 10.1016/j.chroma.2012.07.025
PUBMED : 22840824

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Some epidemiological investigations have revealed that frequent consumption of well-done cooked meats and tobacco smoking are risk factors for breast cancer in women. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a heterocyclic aromatic amine that is formed in well-done cooked meat, and 4-aminobiphenyl (4-ABP) is an aromatic amine that arises in tobacco smoke and occurs as a contaminant in the atmosphere. Both compounds are rodent mammary carcinogens, and putative DNA adducts of PhIP and 4-ABP have been frequently detected, by immunohistochemistry (IHC) or (32)P-post-labeling methods, in mammary tissue of USA women. Because of these findings, PhIP and 4-ABP have been implicated as causal agents of human breast cancer. However, the biomarker data are controversial: both IHC and (32)P-post-labeling are non-selective screening methods and fail to provide confirmatory spectral data. Consequently, the identities of the lesions are equivocal. We employed a specific and sensitive liquid chromatography/mass spectrometry (MS) method, to screen tumor-adjacent normal mammary tissue for DNA adducts of PhIP and 4-ABP. Only 1 of 70 biopsy samples obtained from Minneapolis, Minnesota breast cancer patients contained a PhIP-DNA adduct. The level was three adducts per 10(9) nucleotides, a level that is 100-fold lower than the mean level of PhIP adducts reported by IHC or (32)P-post-labeling methods. The occurrence of 4-ABP-DNA adducts was nil in those same breast tissues. Our findings, derived from a specific mass spectrometry method, signify that PhIP and 4-ABP are not major DNA-damaging agents in mammary tissue of USA women and raise questions about the roles of these chemicals in breast cancer.
ISSN: 0143-3334

hal-00682453
https://hal.archives-ouvertes.fr/hal-00682453
DOI : 10.1093/carcin/bgr252
PUBMED : 22072616

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
ISSN: 0098-0331

hal-01083748
https://hal-agroparistech.archives-ouvertes.fr/hal-01083748
DOI : 10.1007/s10886-009-9673-x