Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves 163-179).

Thesis (Ph. D.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2006. / Dr. Allen M. Orville, Committee Chair ; Dr. Loren D. Williams, Committee Member ; Dr. Dale E. Edmondson, Committee Member ; Dr. Frank E. Lffler, Committee Member ; Dr. Nicholas V. Hud, Committee Member

Orientador: José de Alencar Simoni / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-20T04:40:31Z (GMT). No. of bitstreams: 1 Ullah_Hameed_D.pdf: 3883316 bytes, checksum: 16c65c6adf8cd9be149151992846d83b (MD5) Previous issue date: 2012 / Resumo: O presente estudo investiga a influência da adição de alguns xenobióticos comuns em práticas agrícolas, na atividade microbiana de três solos de diferentes regiões, utilizando a calorimetria isotérmica. Amostras de Latosolo vermelho do Brasil: Unik (Unicamp-Campinas) de mata original, Lebra (Leme-SP) cultivada por algodão, e Pak (Faisalabad, Paquistão) cultivada por algodão. Esses solos foram caracterizados por análise elementar de CHN, pH e acidez total, análise microbiológica e análises térmicas (TGA e DSC). A atividade microbiana foi acompanhada por calorimetria isotérmica, com o objetivo de se investigar a influência de fatores como: tempo de armazenamento, estação de coleta, adição de herbicidas do grupo das sulfoniluréias; clorimuron e metsulfurom, e arsênio. Utilizou-se a glicose como substrato principal, como fonte de carbono, nesse estudo. Os principais resultados evidenciam que o uso dos herbicidas conjuntamente com glicose aumentou a liberação de energia e, portanto, de CO2, quando comparado à adição simples de glicose. A emissão de CO2 (catabolismo) também foi maior para os solos com cultivo intensivo de monocultura de algodão, sendo que a ordem de emissão foi Pak>Lebra>Unik1. Por outro lado a adição de As provoca uma diminuição do catabolismo e, portanto, diminuindo a emissão de CO2 / Abstract: The present study investigates the influence of the addition of some xenobiotics, commonly used in agricultural practices, on the microbial activity of soils from three different regions, by using isothermal calorimetry. Samples of red Latosol from Brazil: Unik (Unicamp-Campinas) of the original forest, Lebra (Leme, São Paulo) cultivated with cotton, and Pak (Faisalabad, Pakistan) cultivated with cotton. These soils were characterized by CHN elemental analysis, pH, total acidity, microbiological analysis and thermal analysis (TGA and DSC). Microbial activity was monitored by isothermal calorimetry, in order to investigate the influence of factors such as time of storage, collection station, the addition of the sulfonylurea herbicides, chlorimuron and metsulfuron, and arsenic ion. Glucose was used as main substrate as carbon source in this study. The main results show that the use of the herbicides together with glucose increased the release of energy, so CO2, compared to the simple addition of glucose. The CO2 emissions (catabolism) was also higher for soils with intensive cultivation of cotton monoculture, and the order was Pak > Lebra > Unik1. Moreover the addition of As causes a decrease in catabolism and thus decreasing the CO2 production to the environment / Doutorado / Físico-Química / Doutor em Ciências

Selected drugs are being utilized as models of putative colon carcinogens in a study of the influence of major types of dietary fiber upon drug pharmacokinetics. Adult, male Wistar rats were pretreated with standardized, isocaloric hydrated gelatin diets containing no fiber or 15% (w/w) cellulose, lignin, hemicellulose (metamucil), or pectin for 30 days. An additional group was fed lab chow ad libitum as a reference control. The pharmacokinetics of acetaminophen, FD & C Red No. 2 and mirex were examined following oral administration in three separate experiments. Among fiber types, pectin and hemicellulose (Metamucil) caused higher peak plasma concentrations of acetaminophen and faster rates of absorption. There was no effect of fiber type on the rate of acetaminophen elimination as determined by the interpretation of the plasma data using the computer programs AUTOAN2 and NONLIN69. Minimal quantities of Red No. 2 were absorbed from the rat intestinal tract, but its microbial metabolite, naphtionic acid, was readily taken up. Pectin produced a 5-fold higher peak plasma concentration of naphthionic acid than control animals on fiber free diet. Cellulose feeding lowered peak plasma concentration of naphthionic acid compared to the fiber control animals. Lack of any fiber in the diet produced a prolonged peak plasma concentration of napthionic acid. The metabolism of Red No. 2 to naphtionic acid by rat cecal contents was augmented by pectin feeding, alone among fiber types. Red No. 2 decreased intestinal transit times in all diet groups, including controls, with there being no difference in transit times between fiber-fed and control animals. Hemicellulose and pectin feeding lowered peak plasma concentrations of mirex compared to control and cellulose fed animals. Lignin, however produced higher peak plasma concentrations of mirex and a 4-fold higher rate of mirex elimination when compared to the fiber-free control group. These differential effects of specific fiber types upon the absorption and disposition of acetaminophen, Red No. 2 and mirex were not consistantly related to the chemical binding-capacities of the fibers of their water-holding capacities.

No description available.

Leung Hau Yi. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 116-131). / Abstracts in English and Chinese. / Thesis Committee --- p.in / Acknowledgement --- p.II / Abstract --- p.III / 摘要 --- p.V / Table of Contents --- p.VII / List of Figures --- p.X / List of Tables --- p.XIII / Appendix Abbreviations --- p.XIV / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Breast Cancer --- p.1 / Chapter 1.2 --- Development of Breast Cancer --- p.2 / Chapter 1.3 --- Risk Factors of Breast Cancer --- p.3 / Chapter 1.3.1 --- Age --- p.3 / Chapter 1.3.2 --- Genetic Factors --- p.4 / Chapter 1.3.3 --- Hormonal Factors --- p.5 / Chapter 1.3.4 --- Lifestyles --- p.6 / Chapter 1.4 --- Drug Metabolism --- p.6 / Chapter 1.5 --- UGT1A1 --- p.7 / Chapter 1.5.1 --- UDP-glucuronosyltransferase --- p.7 / Chapter 1.5.2 --- UGT1A1 --- p.9 / Chapter 1.6 --- Cytochrome P450 I Enzyme Family --- p.10 / Chapter 1.6.1 --- CYP450 subfamily --- p.10 / Chapter 1.6.2 --- CYP1A1 --- p.11 / Chapter 1.6.3 --- CYP1B1 --- p.12 / Chapter 1.7 --- Reasons why UGT1A1 is being studied --- p.13 / Chapter 1.8 --- Outline of this Study --- p.14 / Chapter 1.8.1 --- Effects of Over-expressing UDP-Glucuronpsyltransferase and Cytochrome P450 1A1 Against Xenobiotic Assault in Breast Cancer Cells --- p.14 / Chapter 1.8.2 --- Effects of Genistein and Resveratrol on Phase I and II Enzymes in a Non-cancerous Breast Cell Line --- p.15 / Chapter 1.8.3 --- Effects of UGT1A1 on Cancer Drug Treatment --- p.15 / Chapter Chapter 2 --- Materials and Methods --- p.16 / Chapter 2.1 --- Chemicals --- p.16 / Chapter 2.2 --- Cell Culture --- p.16 / Chapter 2.2.1 --- Maintenance --- p.16 / Chapter 2.2.2 --- Preparation of Cell Stock --- p.17 / Chapter 2.2.3 --- Cell Recovery from Liquid Nitrogen Stock --- p.17 / Chapter 2.3 --- Cloning and Transfection --- p.18 / Chapter 2.3.1 --- Isolation of RNA from cells and cDNA synthesis --- p.18 / Chapter 2.3.2 --- Amplification of UGTlAl --- p.20 / Chapter 2.3.3 --- Separation and Purification of DNA from Agarose Gel --- p.21 / Chapter 2.3.4 --- Restriction Digestion --- p.22 / Chapter 2.3.5 --- Ligation of DNA Fragment and Vector --- p.22 / Chapter 2.3.6 --- Transformation of DH5a --- p.23 / Chapter 2.3.7 --- Small Scale Plasmid Purification (Miniprep) --- p.24 / Chapter 2.3.8 --- Large Scale Plasmid Purification (Maxiprep) --- p.25 / Chapter 2.3.9 --- Stable Transfection into MCF-7 cells with LipofectAMINE PLUS reagent --- p.26 / Chapter 2.4 --- Analytical Procedures --- p.27 / Chapter 2.4.1 --- Western Blot Analysis --- p.27 / Chapter 2.4.2 --- Measurement of cell proliferation (MTT assay) --- p.28 / Chapter 2.4.3 --- Measurement of DMBA-DNA Adduct Formation --- p.28 / Chapter 2.4.4 --- Comet Assay --- p.29 / Chapter 2.4.5 --- Relative Quantitative Real Time PCR --- p.30 / Chapter 2.4.5.1 --- Real Time PCR Using TaqMan Probe --- p.30 / Chapter 2.4.5.2 --- Statistical Analysis of 2-ΔΔCT Comparative Gene Expression --- p.31 / Chapter 2.4.6 --- Flow Cytometry --- p.31 / Chapter 2.4.7 --- EROD Activity in Intact Cells --- p.31 / Chapter 2.4.8 --- High Performance Liquid Chromatography --- p.32 / Chapter 2.5 --- Statistical Analysis --- p.34 / Chapter Chapter 3 --- Effects of Over-Expressing UDP-GIucuronosyltransferase and Cytochrome P450 1A1 Against Xenobiotic Assault in Breast Cancer Cells --- p.35 / Chapter 3.1 --- Introduction --- p.35 / Chapter 3.2 --- Results --- p.38 / Chapter 3.2.1 --- Effectiveness of Transfection --- p.38 / Chapter 3.2.2 --- Cell Proliferation Experiments --- p.41 / Chapter 3.2.3 --- Regulation of Estrogen Receptor (ER) Expression --- p.43 / Chapter 3.2.4 --- Formation of DMBA-DNA adduct formation --- p.45 / Chapter 3.2.5 --- Single Cell Gel Electrophoresis (Comet Assay) of DMBA-induced DNA Damage in MCF-7UGT1A1 cells --- p.46 / Chapter 3.2.6 --- HPLC for Estradiol-glucuronidation Analysis --- p.49 / Chapter 3.2.7 --- Single Cell Gel Electrophoresis (Comet Assay) of DMBA or E2-induced DNA Damage in MCF-7cyp1A1 cells --- p.51 / Chapter 3.3 --- Discussion --- p.56 / Chapter Chapter 4 --- Effects of Genistein and Resveratrol on Phase I and II Enzymes in a Non-Cancerous Breast Cell Line --- p.61 / Chapter 4.1 --- Introduction --- p.61 / Chapter 4.2 --- Results --- p.66 / Chapter 4.2.1 --- "Genistein and Resveratrol Reduced DMBA-induced UGT1A1, CYP1A1 and CYP1B1 Expression" --- p.66 / Chapter 4.2.2 --- Genistein and Resveratrol Reduced the Formation of DMBA-DNA Adduct in MCF-10A Cells --- p.73 / Chapter 4.2.3 --- Genistein and Resveratrol Reduced the Single Strand DNA Damage Generated by DMBA in MCF-10A Cells --- p.76 / Chapter 4.2.4 --- Genistein and Resveratrol Reduced DMBA-induced EROD Activities --- p.81 / Chapter 4.3 --- Discussion --- p.84 / Chapter Chapter 5 --- Effects of Ugtlal on Cancer Drug Treatment --- p.89 / Chapter 5.1 --- Introduction --- p.89 / Chapter 5.2 --- Results --- p.93 / Chapter 5.2.1 --- Cell Proliferation Experiment --- p.93 / Chapter 5.2.2 --- "Expression of Bcl-2 and Bax proteins in Paclitaxel- or VCR-treated MCF-7, MCF-7control and MCF-7UGt1A1 cells" --- p.98 / Chapter 5.2.3 --- Flow Cytometric Analysis of Cell Cycle Phase Distributionin Paclitaxel- or VCR-treated MCF-7 cells --- p.103 / Chapter 5.3 --- Discussion --- p.110 / Chapter Chapter 6 --- Summary --- p.114 / Bibliography --- p.116

Thorough investigation of the glycine conjugation pathway has been neglected over the last 30 years. Environmental factors, nutrition, and the chronic use of medications are increasing the exposure of humans to benzoate and drugs that are metabolized to acyl-CoA intermediates. Glycine conjugation of mitochondrial acyl-CoAs, catalysed by glycine N-acyltransferase (GLYAT, E.C. 2.3.1.13), is an important metabolic pathway responsible for maintaining adequate levels of free coenzyme A (CoASH). However, because of the small number of pharmaceutical drugs that are conjugated to glycine, the pathway has not yet been characterised in detail. Therefore, one of the objectives of this thesis was to develop a better understanding of glycine conjugation and its role in metabolism. In humans and animals a number of endogenous and xenobiotic organic acids are conjugated to glycine. Glycine conjugation has generally been assumed to be a detoxification mechanism, increasing the water solubility of organic acids in order to facilitate urinary excretion. However, recently it was proposed that the role of the amino acid conjugations, including glycine conjugation, is to regulate systemic levels of amino acids that are also utilised as neurotransmitters in the central nervous systems of animals. The glycine deportation hypothesis was based on the observation that, compared to glucuronidation, glycine conjugation does not significantly increase the water solubility of aromatic acids. A thorough review of the literature for this thesis showed that the major role of glycine conjugation, however, is to dispose of the end products of phenylpropionate metabolism. The review also introduced the new perspective that mitochondrial glycine conjugation prevents the accumulation of benzoate in the mitochondrial matrix by forming hippuric acid a less lipophilic conjugate that can be more readily transported out of the mitochondria. Although organic anion transporters can export benzoate from the matrix, this process would likely be futile because benzoic acid can simply diffuse back into the matrix. Hippurate, however, is significantly less lipophilic and therefore less capable of diffusing into the matrix. It is therefore not the transport out of the mitochondrial matrix that is facilitated by glycine conjugation, but rather the ability of the glycine conjugates to re-enter the matrix that is decreased. Lastly, glycine conjugation of benzoate also exacerbates the dietary deficiency of glycine in humans. Because the resulting shortage of glycine can negatively influence brain neurochemistry and the synthesis of collagen, nucleic acids, porphyrins, and other important metabolites, the risks of using benzoate as a preservative should not be underestimated. To date, no defect of the glycine conjugation pathway has been reported and this, together with the fact that GLYAT plays an important role in hepatic metabolism, suggests that this pathway is essential for survival. GLYAT activity affects mitochondrial ATP production, glycine availability, CoASH availability and the toxicity of various organic acids. Therefore, variation in the glycine conjugation pathway could influence liver cancer, musculoskeletal development and mitochondrial energy metabolism. Significant interindividual variation exists in glycine conjugation capacity. The molecular basis for this variability is not known. The main aim of this thesis was to investigate and characterise the genetic variation in the coding region of the GLYAT gene. This was accomplished by firstly, investigating the influence of non-synonymous single nucleotide polymorphisms (SNPs) on the enzyme activity of a recombinant human GLYAT and secondly, by analysing the level of genetic variation in the coding region of the GLYAT gene using existing worldwide population data. To investigate the influence of non-synonymous SNPs in the GLYAT gene on the enzyme activity, a recombinant human GLYAT was prepared, and characterised. Site-directed mutagenesis was used to generate six variants of the enzyme (K16N; S17T; R131H; N156S; F168L; R199C). The variants were expressed, purified, and enzymatically characterised. The enzyme activities of the K16N, S17T and R131H variants were similar to that of the wild-type, whereas the N156S variant was more active, the F168L variant less active, and the R199C variant was inactive. The results showed that SNP variations in the human GLYAT gene can influence the kinetic properties of the enzyme. The genetic variation data of the human GLYAT open reading frame (ORF) available on public databases was investigated by formulating the hypothesis that due to the essential nature of the glycine conjugation pathway, the genetic variation in the ORF of the GLYAT gene should be low and that deleterious alleles will be found at low frequencies. Data from the i) 1000 Genome Project, ii) the HapMap Project, and iii) the Khoi-San/Bantu Sequencing Project was downloaded from available databases. Sequence data of the coding region of a small cohort of South African Afrikaner Caucasian individuals was also generated and included in the analyses. In the GLYAT ORF of the 1537 individuals analysed, only two haplotypes (S156 and T17S156) out of 14 haplotypes were identified in all populations as having the highest haplotype frequencies (70% and 20% respectively). The S156C199 and S156H131 haplotypes, which have a deleterious effect on the enzyme activity of a recombinant human GLYAT, were detected at very low frequencies. The results of this study indicated that the GLYAT ORF is remarkably conserved, which supports the hypothesis that the glycine conjugation pathway is an essential detoxification pathway. The findings presented in this thesis highlight the importance that future investigations should determine the in vivo capacity of the glycine conjugation pathway for the detoxification of benzoate and other xenobiotics. / PhD (Biochemistry), North-West University, Potchefstroom Campus, 2015

Thorough investigation of the glycine conjugation pathway has been neglected over the last 30 years. Environmental factors, nutrition, and the chronic use of medications are increasing the exposure of humans to benzoate and drugs that are metabolized to acyl-CoA intermediates. Glycine conjugation of mitochondrial acyl-CoAs, catalysed by glycine N-acyltransferase (GLYAT, E.C. 2.3.1.13), is an important metabolic pathway responsible for maintaining adequate levels of free coenzyme A (CoASH). However, because of the small number of pharmaceutical drugs that are conjugated to glycine, the pathway has not yet been characterised in detail. Therefore, one of the objectives of this thesis was to develop a better understanding of glycine conjugation and its role in metabolism. In humans and animals a number of endogenous and xenobiotic organic acids are conjugated to glycine. Glycine conjugation has generally been assumed to be a detoxification mechanism, increasing the water solubility of organic acids in order to facilitate urinary excretion. However, recently it was proposed that the role of the amino acid conjugations, including glycine conjugation, is to regulate systemic levels of amino acids that are also utilised as neurotransmitters in the central nervous systems of animals. The glycine deportation hypothesis was based on the observation that, compared to glucuronidation, glycine conjugation does not significantly increase the water solubility of aromatic acids. A thorough review of the literature for this thesis showed that the major role of glycine conjugation, however, is to dispose of the end products of phenylpropionate metabolism. The review also introduced the new perspective that mitochondrial glycine conjugation prevents the accumulation of benzoate in the mitochondrial matrix by forming hippuric acid a less lipophilic conjugate that can be more readily transported out of the mitochondria. Although organic anion transporters can export benzoate from the matrix, this process would likely be futile because benzoic acid can simply diffuse back into the matrix. Hippurate, however, is significantly less lipophilic and therefore less capable of diffusing into the matrix. It is therefore not the transport out of the mitochondrial matrix that is facilitated by glycine conjugation, but rather the ability of the glycine conjugates to re-enter the matrix that is decreased. Lastly, glycine conjugation of benzoate also exacerbates the dietary deficiency of glycine in humans. Because the resulting shortage of glycine can negatively influence brain neurochemistry and the synthesis of collagen, nucleic acids, porphyrins, and other important metabolites, the risks of using benzoate as a preservative should not be underestimated. To date, no defect of the glycine conjugation pathway has been reported and this, together with the fact that GLYAT plays an important role in hepatic metabolism, suggests that this pathway is essential for survival. GLYAT activity affects mitochondrial ATP production, glycine availability, CoASH availability and the toxicity of various organic acids. Therefore, variation in the glycine conjugation pathway could influence liver cancer, musculoskeletal development and mitochondrial energy metabolism. Significant interindividual variation exists in glycine conjugation capacity. The molecular basis for this variability is not known. The main aim of this thesis was to investigate and characterise the genetic variation in the coding region of the GLYAT gene. This was accomplished by firstly, investigating the influence of non-synonymous single nucleotide polymorphisms (SNPs) on the enzyme activity of a recombinant human GLYAT and secondly, by analysing the level of genetic variation in the coding region of the GLYAT gene using existing worldwide population data. To investigate the influence of non-synonymous SNPs in the GLYAT gene on the enzyme activity, a recombinant human GLYAT was prepared, and characterised. Site-directed mutagenesis was used to generate six variants of the enzyme (K16N; S17T; R131H; N156S; F168L; R199C). The variants were expressed, purified, and enzymatically characterised. The enzyme activities of the K16N, S17T and R131H variants were similar to that of the wild-type, whereas the N156S variant was more active, the F168L variant less active, and the R199C variant was inactive. The results showed that SNP variations in the human GLYAT gene can influence the kinetic properties of the enzyme. The genetic variation data of the human GLYAT open reading frame (ORF) available on public databases was investigated by formulating the hypothesis that due to the essential nature of the glycine conjugation pathway, the genetic variation in the ORF of the GLYAT gene should be low and that deleterious alleles will be found at low frequencies. Data from the i) 1000 Genome Project, ii) the HapMap Project, and iii) the Khoi-San/Bantu Sequencing Project was downloaded from available databases. Sequence data of the coding region of a small cohort of South African Afrikaner Caucasian individuals was also generated and included in the analyses. In the GLYAT ORF of the 1537 individuals analysed, only two haplotypes (S156 and T17S156) out of 14 haplotypes were identified in all populations as having the highest haplotype frequencies (70% and 20% respectively). The S156C199 and S156H131 haplotypes, which have a deleterious effect on the enzyme activity of a recombinant human GLYAT, were detected at very low frequencies. The results of this study indicated that the GLYAT ORF is remarkably conserved, which supports the hypothesis that the glycine conjugation pathway is an essential detoxification pathway. The findings presented in this thesis highlight the importance that future investigations should determine the in vivo capacity of the glycine conjugation pathway for the detoxification of benzoate and other xenobiotics. / PhD (Biochemistry), North-West University, Potchefstroom Campus, 2015

La transition épithélio-mésenchymateuse (TEM) est un processus qui interviendrait lors des étapes précoces (fibrose) et tardives (métastases) de cancérogenèse. Elle consiste en la perte des caractères cellulaires épithéliaux tels que les jonctions adhérentes, pour le gain de propriétés mésenchymateuses, et confère ainsi aux cellules la capacité de migration et d'invasion. Nos travaux ont eu pour objectifs d'identifier et de caractériser, sur des cellules d'origine hépatique, des biomarqueurs de TEM, afin d'évaluer de manière prédictive et fiable les effets pro-tumoraux de contaminants chimiques environnementaux. Nous avons d'abord décrypté les évènements cellulaires et moléculaires intervenant en réponse à des inducteurs de TEM, tels que le TPA sur la lignée HepG2 et le TGFβ sur des hépatocytes humains en culture primaire. Puis, combinés à l'utilisation d'une technologie innovante de mesure de l'impédance cellulaire en temps réel et à d'autres biomarqueurs (apoptose, cycle cellulaire…), ces travaux nous ont permis d'estimer l'impact de pesticides dans l'initiation de la TEM et leur potentiel cancérogène sur le foie. / The epithelial to mesenchymal transition (EMT) is a process that occurs during the early (fibrosis) and late (metastases) stages of carcinogenesis. It is defined as the loss of epithelial characteristics such as cell adherent junctions and the gain of mesenchymal properties, thereby conferring to cells the ability to migrate and invade. Our objectives were to identify and characterize, in hepatic cells, EMT biomarkers that could reliably predict pro-tumoral effects of environmental chemical contaminants. We first characterized the cellular and molecular events that occur in response to EMT inducers, such as TPA on cell line HepG2 and TGFβ on human hepatocytes in primary culture. Then, using an innovative technology capable of measuring real time cellular impedance alongside other biomarkers of such as apoptosis and the cell cycle, we estimated the impact of pesticides on EMT and assessed their carcinogenic potential on liver.

Le but de notre étude était de mettre en place une méthode qui puisse nous permettre d’identifier, en aveugle, des perturbateurs de voies biologiques, et qui soit d’une part généralisable pour toute espèce de poissons et d’autre part applicable quel que soit le cours d’eau considéré. Nous nous sommes intéressés aux gènes différentiellement exprimés dans le foie, en utilisant la technologie du séquençage Illumina de banques ADNc. Nous avons étudié trois espèces de cyprinidae (C. nasus, P. toxostoma, S. cephalus) dans le bassin de la Durance, servant à l’alimentation en eau de plusieurs millions de personnes. Nous avons mis en place une suite logicielle pour inférer un transcriptome pour chacune des trois espèces étudiées, et effectué un travail en bioinformatique pour l’identification des spécimens hybrides. Cette méthode nous permet d’assigner les 596 millions de séquences générées (293 spécimens) à l’une des trois espèces et à 16606 gènes identifiés. Les résultats biologiques montrent des variations de l’expression de gènes touchant des voies biologiques associées à des réponses aux xénobiotiques le long de l’axe amont-aval de la rivière. Ils montrent aussi que les spécimens échantillonnés dans le canal EDF présentent des réponses atténuées aux xénobiotiques par rapport aux individus en rivière. Ce résultat peut s’expliquer par l’effet de dilution des polluants dans une masse d’eau plus importante. Cette étude met en évidence les capacités adaptatives des populations de poissons à court terme, via des modifications de l’expression des gènes à un ensemble de perturbateurs environnementaux. Ce travail permet d’envisager la mise en place d’un outil de gestion incontournable. / The aim of our study was to establish a method that allows the identification (in blind) of biologicalpathway disrupters, for all species of fish and applicable regardless of the watercourse considered. Wefocused on differentially expressed genes (and the biological pathways in which they act) in the liver,using the Illumina sequencing technology of cDNA libraries. We studied three species of cyprinidae (C.nasus, P. toxostoma, S. cephalus) in the Durance basin that constitutes water resource for several millionpeople. We have implemented a pipeline to infer the transcriptome for each of the three species studied,and developed a bioinformatics framework for the identification of hybrid specimens. This methodallows us to assign the 596 million sequences generated (representing 293 specimens) to one of the threespecies and to 16,606 identified genes. The biological results display variations in the expression of genesaffecting biological pathways associated with xenobiotic responses (estrogens, Hap, heavy metals) alongthe upstream-downstream axis of the river. They also yield that the specimens sampled in the EDFchannel displayed an attenuated responses to xenobiotics, in comparison to individuals that inhabitethe river, possibly a benefit of the dilution effect of pollutants in a larger body of water. This studyhighlights short-term adaptive capacities (acclimation) of fish populations to a set of environmentaldisrupters via changes in gene expression levels. It will open a way to an essential tool for managementpolicies.