A Preliminary Investigation on the Chemical Composition of the Cell Surface of Five Enteropathogenic Escherichia coli Serotypes

The cell surfaces of five enteropathogenic Escherichia coli serotypes (O111:H2; O111:H12; O125:H9; O119:H6; O26:H11) were assayed by chemical methods, lectin agglutination tests and spectroscopy associated to transmission electron microscopy. Results of lectin agglutination assays showed that all strains reacted with mannosebinding lectins. Strains belonging to serotype O125:H9 also agglutinated with lectins which recognize galactose and Nacetylgalactosamine residues. The bacterial cells were treated with 0.01M phosphate buffered saline (pH 7.0) at 100oC for 2 hr and the extracts were submitted to precipitation and fractionated by Cetavlon. Phosphate, total sugar and protein contents were determined. Gas liquid chomatography-mass spectrometry analysis of alditol acetates showed the presence of galactose, mannose, fucose, glucose and traces of ribose. Spectroscopic analysis of intact cells showed the presence of a capsule-like structure which was not totally preserved after extraction. Some cells were still surrounded by an amorphous capsular-like material after polysaccharide extraction.

Evaluation of exposure biomarkers in offshore workers exposed to low benzene and toluene concentrations.

Characterize ethylbenzene and xylene air concentrations, and explore the biological exposure markers (urinary t,t-muconic acid (t,t-MA) and unmetabolized toluene) among petroleum workers offshore. Offshore workers have increased health risks due to simultaneous exposures to several hydrocarbons present in crude oil. We discuss the pooled benzene exposure results from our previous and current studies and possible co-exposure interactions. BTEX air concentrations were measured during three consecutive 12-h work shifts among 10 tank workers, 15 process operators, and 18 controls. Biological samples were collected pre-shift on the first day of study and post-shift on the third day of the study. The geometric mean exposure over the three work shifts were 0.02 ppm benzene, 0.05 ppm toluene, 0.03 ppm ethylbenzene, and 0.06 ppm xylene. Benzene in air was significantly correlated with unmetabolized benzene in blood (r = 0.69, p < 0.001) and urine (r = 0.64, p < 0.001), but not with urinary t,t-MA (r = 0.27, p = 0.20). Toluene in air was highly correlated with the internal dose of toluene in both blood (r = 0.70, p < 0.001) and urine (r = 0.73, p < 0.001). Co-exposures were present; however, an interaction of metabolism was not likely at these low benzene and toluene exposures. Urinary benzene, but not t,t-MA, was a reliable biomarker for benzene at low exposure levels. Urinary toluene was a useful biomarker for toluene exposure. Xylene and ethylbenzene air levels were low. Dermal exposure assessment needs to be performed in future studies among these workers.

Solid phase microextraction as a short-term sampling technique for BTEX occupational exposure

Solid phase microextraction (SPME) has been widely used for many years in various applications, such as environmental and water samples, food and fragrance analysis, or biological fluids. The aim of this study was to suggest the SPME method as an alternative to conventional techniques used in the evaluation of worker exposure to benzene, toluene, ethylbenzene, and xylene (BTEX). Polymethylsiloxane-carboxen (PDMS/CAR) showed as the most effective stationary phase material for sorbing BTEX among other materials (polyacrylate, PDMS, PDMS/divinylbenzene, Carbowax/divinylbenzene). Various experimental conditions were studied to apply SPME to BTEX quantitation in field situations. The uptake rate of the selected fiber (75 microm PDMS/CAR) was determined for each analyte at various concentrations, relative humidities, and airflow velocities from static (calm air) to dynamic (> 200 cm/s) conditions. The SPME method also was compared with the National Institute of Occupational Safety and Health method 1501. Unlike the latter, the SPME approach fulfills the new requirement for the threshold limit value-short term exposure limit (TLV-STEL) of 2.5 ppm for benzene (8 mg/m(3))

Whole-body protein turnover and resting energy expenditure in obese, prepubertal children.

BACKGROUND: Obesity is becoming more frequent in children; understanding the extent to which this condition affects not only carbohydrate and lipid metabolism but also protein metabolism is of paramount importance. OBJECTIVE: We evaluated the kinetics of protein metabolism in obese, prepubertal children in the static phase of obesity. DESIGN: In this cross-sectional study, 9 obese children (x +/- SE: 44+/-4 kg, 30.9+/-1.5% body fat) were compared with 8 lean (28+/-2 kg ,16.8+/-1.2% body fat), age-matched (8.5+/-0.2 y) control children. Whole-body nitrogen flux, protein synthesis, and protein breakdown were calculated postprandially over 9 h from 15N abundance in urinary ammonia by using a single oral dose of [15N]glycine; resting energy expenditure (REE) was assessed by indirect calorimetry (canopy) and body composition by multiple skinfold-thickness measurements. RESULTS: Absolute rates of protein synthesis and breakdown were significantly greater in obese children than in control children (x +/- SE: 208+/-24 compared with 137+/-14 g/d, P < 0.05, and 149+/-20 compared with 89+/-13 g/d, P < 0.05, respectively). When these variables were adjusted for fat-free mass by analysis of covariance, however, the differences between groups disappeared. There was a significant relation between protein synthesis and fat-free mass (r = 0.83, P < 0.001) as well as between protein synthesis and REE (r = 0.79, P < 0.005). CONCLUSIONS: Obesity in prepubertal children is associated with an absolute increase in whole-body protein turnover that is consistent with an absolute increase in fat-free mass, both of which contribute to explaining the greater absolute REE in obese children than in control children.

Occupational respiratory exposures to irritating and sensitizing volatile compounds deriving from cleaning products

Recent findings suggest an association between exposure to cleaning products and respiratory dysfunctions including asthma. However, little information is available about quantitative airborne exposures of professional cleaners to volatile organic compounds deriving from cleaning products. During the first phases of the study, a systematic review of cleaning products was performed. Safety data sheets were reviewed to assess the most frequently added volatile organic compounds. It was found that professional cleaning products are complex mixtures of different components (compounds in cleaning products: 3.5 ± 2.8), and more than 130 chemical substances listed in the safety data sheets were identified in 105 products. The main groups of chemicals were fragrances, glycol ethers, surfactants, solvents; and to a lesser extent phosphates, salts, detergents, pH-stabilizers, acids, and bases. Up to 75% of products contained irritant (Xi), 64% harmful (Xn) and 28% corrosive (C) labeled substances. Hazards for eyes (59%), skin (50%) and by ingestion (60%) were the most reported. Monoethanolamine, a strong irritant and known to be involved in sensitizing mechanisms as well as allergic reactions, is frequently added to cleaning products. Monoethanolamine determination in air has traditionally been difficult and air sampling and analysis methods available were little adapted for personal occupational air concentration assessments. A convenient method was developed with air sampling on impregnated glass fiber filters followed by one step desorption, gas chromatography and nitrogen phosphorous selective detection. An exposure assessment was conducted in the cleaning sector, to determine airborne concentrations of monoethanolamine, glycol ethers, and benzyl alcohol during different cleaning tasks performed by professional cleaning workers in different companies, and to determine background air concentrations of formaldehyde, a known indoor air contaminant. The occupational exposure study was carried out in 12 cleaning companies, and personal air samples were collected for monoethanolamine (n=68), glycol ethers (n=79), benzyl alcohol (n=15) and formaldehyde (n=45). All but ethylene glycol mono-n-butyl ether air concentrations measured were far below (<1/10) of the Swiss eight hours occupational exposure limits, except for butoxypropanol and benzyl alcohol, where no occupational exposure limits were available. Although only detected once, ethylene glycol mono-n-butyl ether air concentrations (n=4) were high (49.5 mg/m3 to 58.7 mg/m3), hovering at the Swiss occupational exposure limit (49 mg/m3). Background air concentrations showed no presence of monoethanolamine, while the glycol ethers were often present, and formaldehyde was universally detected. Exposures were influenced by the amount of monoethanolamine in the cleaning product, cross ventilation and spraying. The collected data was used to test an already existing exposure modeling tool during the last phases of the study. The exposure estimation of the so called Bayesian tool converged with the measured range of exposure the more air concentrations of measured exposure were added. This was best described by an inverse 2nd order equation. The results suggest that the Bayesian tool is not adapted to predict low exposures. The Bayesian tool should be tested also with other datasets describing higher exposures. Low exposures to different chemical sensitizers and irritants should be further investigated to better understand the development of respiratory disorders in cleaning workers. Prevention measures should especially focus on incorrect use of cleaning products, to avoid high air concentrations at the exposure limits. - De récentes études montrent l'existence d'un lien entre l'exposition aux produits de nettoyages et les maladies respiratoires telles que l'asthme. En revanche, encore peu d'informations sont disponibles concernant la quantité d'exposition des professionnels du secteur du nettoyage aux composants organiques volatiles provenant des produits qu'ils utilisent. Pendant la première phase de cette étude, un recueil systématique des produits professionnels utilisés dans le secteur du nettoyage a été effectué. Les fiches de données de sécurité de ces produits ont ensuite été analysées, afin de répertorier les composés organiques volatiles les plus souvent utilisés. Il a été mis en évidence que les produits de nettoyage professionnels sont des mélanges complexes de composants chimiques (composants chimiques dans les produits de nettoyage : 3.5 ± 2.8). Ainsi, plus de 130 substances listées dans les fiches de données de sécurité ont été retrouvées dans les 105 produits répertoriés. Les principales classes de substances chimiques identifiées étaient les parfums, les éthers de glycol, les agents de surface et les solvants; dans une moindre mesure, les phosphates, les sels, les détergents, les régulateurs de pH, les acides et les bases ont été identifiés. Plus de 75% des produits répertoriés contenaient des substances décrites comme irritantes (Xi), 64% nuisibles (Xn) et 28% corrosives (C). Les risques pour les yeux (59%), la peau (50%) et par ingestion (60%) était les plus mentionnés. La monoéthanolamine, un fort irritant connu pour être impliqué dans les mécanismes de sensibilisation tels que les réactions allergiques, est fréquemment ajouté aux produits de nettoyage. L'analyse de la monoéthanolamine dans l'air a été habituellement difficile et les échantillons d'air ainsi que les méthodes d'analyse déjà disponibles étaient peu adaptées à l'évaluation de la concentration individuelle d'air aux postes de travail. Une nouvelle méthode plus efficace a donc été développée en captant les échantillons d'air sur des filtres de fibre de verre imprégnés, suivi par une étape de désorption, puis une Chromatographie des gaz et enfin une détection sélective des composants d'azote. Une évaluation de l'exposition des professionnels a été réalisée dans le secteur du nettoyage afin de déterminer la concentration atmosphérique en monoéthanolamine, en éthers de glycol et en alcool benzylique au cours des différentes tâches de nettoyage effectuées par les professionnels du nettoyage dans différentes entreprises, ainsi que pour déterminer les concentrations atmosphériques de fond en formaldéhyde, un polluant de l'air intérieur bien connu. L'étude de l'exposition professionnelle a été effectuée dans 12 compagnies de nettoyage et les échantillons d'air individuels ont été collectés pour l'éthanolamine (n=68), les éthers de glycol (n=79), l'alcool benzylique (n=15) et le formaldéhyde (n=45). Toutes les substances mesurées dans l'air, excepté le 2-butoxyéthanol, étaient en-dessous (<1/10) de la valeur moyenne d'exposition aux postes de travail en Suisse (8 heures), excepté pour le butoxypropanol et l'alcool benzylique, pour lesquels aucune valeur limite d'exposition n'était disponible. Bien que détecté qu'une seule fois, les concentrations d'air de 2-butoxyéthanol (n=4) étaient élevées (49,5 mg/m3 à 58,7 mg/m3), se situant au-dessus de la frontière des valeurs limites d'exposition aux postes de travail en Suisse (49 mg/m3). Les concentrations d'air de fond n'ont montré aucune présence de monoéthanolamine, alors que les éthers de glycol étaient souvent présents et les formaldéhydes quasiment toujours détectés. L'exposition des professionnels a été influencée par la quantité de monoéthanolamine présente dans les produits de nettoyage utilisés, par la ventilation extérieure et par l'emploie de sprays. Durant la dernière phase de l'étude, les informations collectées ont été utilisées pour tester un outil de modélisation de l'exposition déjà existant, l'outil de Bayesian. L'estimation de l'exposition de cet outil convergeait avec l'exposition mesurée. Cela a été le mieux décrit par une équation du second degré inversée. Les résultats suggèrent que l'outil de Bayesian n'est pas adapté pour mettre en évidence les taux d'expositions faibles. Cet outil devrait également être testé avec d'autres ensembles de données décrivant des taux d'expositions plus élevés. L'exposition répétée à des substances chimiques ayant des propriétés irritatives et sensibilisantes devrait être investiguée d'avantage, afin de mieux comprendre l'apparition de maladies respiratoires chez les professionnels du nettoyage. Des mesures de prévention devraient tout particulièrement être orientées sur l'utilisation correcte des produits de nettoyage, afin d'éviter les concentrations d'air élevées se situant à la valeur limite d'exposition acceptée.

First-passage times for non-Markovian processes: Correlated impacts on bound processes

Our previously developed stochastic trajectory analysis technique has been applied to the calculation of first-passage time statistics of bound processes. Explicit results are obtained for linearly bound processes driven by dichotomous fluctuations having exponential and rectangular temporal distributions.

First-passage times for non-Markovian processes: Shot noise

The stochastic-trajectory-analysis technique is applied to the calculation of the mean¿first-passage-time statistics for processes driven by external shot noise. Explicit analytical expressions are obtained for free and bound processes.

Genetic vulnerability factor for schizophrenia: association with glutamate cysteine ligase modifier gene and abnormal enzyme activity

Background: We previously reported in schizophrenia patients a decreased level of glutathione ([GSH]), the principal non-protein antioxidant and redox regulator, both in cerebrospinal-fluid and prefrontal cortex. To identify possible genetic causation, we studied genes involved in GSH metabolism. Methods: Genotyping: mass spectrometry analysis of polymerase chain reaction (PCR) amplified DNA fragments purified from peripheral blood. Gene expression: real-time PCR of total RNA isolated from fibroblast cultures derived from skin of patients (DSM-IV) and healthy controls (DIGS). Results: Case-control association study of single nucleotide polymorphisms (SNP) from the GSH key synthesizing enzyme glutamate-cysteine-ligase (GCL) modifier subunit (GCLM) was performed in two populations: Swiss (patients/controls: 40/31) and Danish (349/348). We found a strong association of SNP rs2301022 in GCLM gene (Danish: c2=3.2; P=0.001 after correction for multiple testing). Evidence for GCLM as a risk factor was confirmed in linkage study of NIMH families. Moreover, we observed a decrease in GCLM mRNA levels in patient fibroblasts, consistently with the association study. Interestingly, Dalton and collaborators reported in GCLM knock-out mice an increased feedback inhibition of GCL activity, resulting in 60% decrease of brain [GSH], a situation analogous to patients. These mice also exhibited an increased sensitivity to oxidative stress. Similarly, under oxidative stress conditions, GCL enzymatic activity was also decreased in patient fibroblasts. Conclusions: These results at the genetic and functional levels, combined with observations that GSH deficient models reveal morphological, electrophysiological, and behavioral anomalies analogous to those observed in patients, suggest that GCLM allelic variant is a vulnerability factor for schizophrenia.

Reconstructing snow avalanches in the Southeastern Pyrenees

A regional study of snow avalanche processes was undertaken in the SE Pyrenees. Dendrogeomorphology was used to date and reconstruct large-scale snow avalanche events that occurred in the last four decades. Dendrochronological analyses yielded the dates of nine winters when avalanches occurred in the recent past in six studied avalanche paths. Some of these avalanches were already known, but others had not been documented. In one case, the existing avalanche path map was improved with the dendrogeomorphological information of a larger past event. As a result of the dendrogeomorphological analyses, evidence for three regional-scale major avalanche years was identified in the SE Pyrenees from 1971 to 2004: 1971¿1972, 1995¿1996 and 2002¿2003. The specific synoptic atmospheric situations and the most likely nivometeorological and snowpack conditions that released these major avalanches were determined using weather data for the seasons of major avalanche releases. In 1971¿1972 the snow avalanche episode was characterized by a deep trough crossing the Pyrenees. In 1995¿1996 a variety of meteorological situations produced several episodes of major avalanches. In 2002¿2003 the more significant of two episodes was attributed to a north advection pumping an arctic air mass over the Pyrenees. The 1995¿1996 avalanche season proved to be the most notable in the four past decades in the Pyrenees.

Alterations in Postural Control during the World's Most Challenging Mountain Ultra-Marathon

We investigated postural control (PC) effects of a mountain ultra-marathon (MUM): a 330-km trail run with 24000 m of positive and negative change in elevation. PC was assessed prior to (PRE), during (MID) and after (POST) the MUM in experienced ultra-marathon runners (n = 18; finish time = 126+/-16 h) and in a control group (n = 8) with a similar level of sleep deprivation. Subjects were instructed to stand upright on a posturographic platform over a period of 51.2 seconds using a double-leg stance under two test conditions: eyes open (EO) and eyes closed (EC). Traditional measures of postural stability (center of pressure trajectory analysis) and stabilogram-diffusion analysis (SDA) parameters were analysed. For the SDA, a significantly greater short-term effective diffusion was found at POST compared with PRE in the medio-lateral (ML; Dxs) and antero-posterior (AP) directions (Dys) in runners (p<0.05) The critical time interval (Ctx) in the ML direction was significantly higher at MID (p<0.001) and POST (p<0.05) than at PRE in runners. At MID (p<0.001) and POST (p<0.05), there was a significant difference between the two groups. The critical displacement (Cdx) in the ML was significantly higher at MID and at POST (p<0.001) compared with PRE for runners. A significant difference in Cdx was observed between groups in EO at MID (p<0.05) and POST (p<0.005) in the ML direction and in EC at POST in the ML and AP directions (p<0.05). Our findings revealed significant effects of fatigue on PC in runners, including, a significant increase in Ctx (critical time in ML plan) in EO and EC conditions. Thus, runners take longer to stabilise their body at POST than at MID. It is likely that the mountainous characteristics of MUM (unstable ground, primarily uphill/downhill running, and altitude) increase this fatigue, leading to difficulty in maintaining balance.

Exposure to bioaerosols in poultry houses at different stages of fattening; use of real-time PCR for airborne bacterial quantification

Previous studies have demonstrated that poultry house workers are exposed to very high levels of organic dust and consequently have an increased prevalence of adverse respiratory symptoms. However, the influence of the age of broilers on bioaerosol concentrations has not been investigated. To evaluate the evolution of bioaerosol concentration during the fattening period, bioaerosol parameters (inhalable dust, endotoxin and bacteria) were measured in 12 poultry confinement buildings in Switzerland, at three different stages of the birds' growth; samples of air taken from within the breathing zones of individual poultry house employees as they caught the chickens ready to be transported for slaughter were also analysed. Quantitative polymerase chain reaction (Q-PCR) was used to assess the quantity of total airborne bacteria and total airborne Staphylococcus species. Bioaerosol levels increased significantly during the fattening period of the chickens. During the task of catching mature birds, the mean inhalable dust concentration for a worker was 26 +/- 1.9 mg m(-3) and endotoxin concentration was 6198 +/- 2.3 EU m(-3) air, >6-fold higher than the Swiss occupational recommended value (1000 EU m(-3)). The mean exposure level of bird catchers to total bacteria and Staphylococcus species measured by Q-PCR is also very high, respectively, reaching values of 53 (+/-2.6) x 10(7) cells m(-3) air and 62 (+/-1.9) x 10(6) m(-3) air. It was concluded that in the absence of wearing protective breathing apparatus, chicken catchers in Switzerland risk exposure beyond recommended limits for all measured bioaerosol parameters. Moreover, the use of Q-PCR to estimate total and specific numbers of airborne bacteria is a promising tool for evaluating any modifications intended to improve the safety of current working practices

Increased fat oxidation in prepubertal obese children: a metabolic defense against further weight gain?

The purpose of this study was to measure postabsorptive fat oxidation at rest and to assess the association between fat mass and fat oxidation rate in prepubertal children, who were assigned to two groups: 35 obese children (weight, 44.5 +/- 9.7 kg; fat mass; 31.7 +/- 5.4%) and 37 nonobese children (weight, 30.8 +/- 6.8 kg; fat mass, 17.5 +/- 6.7%). Postabsorptive fat oxidation expressed in absolute value was significantly higher in obese than in nonobese children (31.4 +/- 9.7 mg/min vs 21.9 +/- 10.2 mg/min; p < 0.001) but not when adjusted for fat-free mass by analysis of covariance with fat-free mass as the covariate (28.2 +/- 10.6 mg/min vs 24.9 +/- 10.5 mg/min). In obese children and in the total group, fat mass and fat oxidation were significantly correlated (r = 0.65; p < 0.001). The slope of the relationship indicated that for each 10 kg additional fat mass, resting fat oxidation increased by 18 gm/day. We conclude that obese prepubertal children have a higher postabsorptive rate of fat oxidation than nonobese children. This metabolic process may favor the achievement of a new equilibrium in fat balance, opposing further adipose tissue gain.

Kehityspolkuanalyysi tilastollisena menetelmänä : soveltajan näkökulma

Summary: An applied viewpoint to the trajectory analysis method

Structural Insight into the Mode of Action of a Direct Inhibitor of Coregulator Binding to the Thyroid Hormone Receptor.

The development of nuclear hormone receptor antagonists that directly inhibit the association of the receptor with its essential coactivators would allow useful manipulation of nuclear hormone receptor signaling. We previously identified 3-(dibutylamino)-1-(4-hexylphenyl)-propan-1-one (DHPPA), an aromatic β-amino ketone that inhibits coactivator recruitment to thyroid hormone receptor β (TRβ), in a high-throughput screen. Initial evidence suggested that the aromatic β-enone 1-(4-hexylphenyl)-prop-2-en-1-one (HPPE), which alkylates a specific cysteine residue on the TRβ surface, is liberated from DHPPA. Nevertheless, aspects of the mechanism and specificity of action of DHPPA remained unclear. Here, we report an x-ray structure of TRβ with the inhibitor HPPE at 2.3-Å resolution. Unreacted HPPE is located at the interface that normally mediates binding between TRβ and its coactivator. Several lines of evidence, including experiments with TRβ mutants and mass spectroscopic analysis, showed that HPPE specifically alkylates cysteine residue 298 of TRβ, which is located near the activation function-2 pocket. We propose that this covalent adduct formation proceeds through a two-step mechanism: 1) β-elimination to form HPPE; and 2) a covalent bond slowly forms between HPPE and TRβ. DHPPA represents a novel class of potent TRβ antagonist, and its crystal structure suggests new ways to design antagonists that target the assembly of nuclear hormone receptor gene-regulatory complexes and block transcription.

Etude des niveaux de concentration d'hydrocarbures aromatiques polycycliques (HAPs) dans la poussière de bois et des marqueurs biologiques d'effets génotoxiques chez les travailleurs du bois

L'exposition aux poussières de bois est associé à un risque accru d'adénocarcinomes des fosses nasales et des sinus paranasaux (SNC, 'Sinonasal cancer') chez les travailleurs du bois. Les poussières de bois sont ainsi reconnues comme cancérogènes avérés pour l'homme par le Centre international de Recherche sur le Cancer (CIRC). Toutefois, l'agent causal spécifique et le mécanisme sous-jacent relatifs au cancer lié aux poussières de bois demeurent inconnus. Une possible explication est une co-exposition aux poussières de bois et aux Hydrocarbures Aromatiques Polycycliques (HAP), ces derniers étant potentiellement cancérogènes. Dans les faits, les travailleurs du bois sont non seulement exposés aux poussières de bois naturel, mais également à celles générées lors d'opérations effectuées à l'aide de machines (ponceuses, scies électriques, etc.) sur des finitions de bois (bois traités) ou sur des bois composites, tels que le mélaminé et les panneaux de fibres à densité moyenne (MDF, 'Medium Density Fiberboard'). Des HAP peuvent en effet être générés par la chaleur produite par l'utilisation de ces machines sur la surface du bois. Les principaux objectifs de cette thèse sont les suivants: (1) quantifier HAP qui sont présents dans les poussières générées lors de diverses opérations courantes effectuées sur différents bois (2) quantifier l'exposition individuelle aux poussières de bois et aux HAP chez les travailleurs, et (3) évaluer les effets génotoxiques (dommages au niveau de l'ADN et des chromosomes) due à l'exposition aux poussières de bois et aux HAP. Cette thèse est composée par une étude en laboratoire (objectif 1) et par une étude de terrain (objectifs 2 et 3). Pour l'étude en laboratoire, nous avons collecté des poussières de différents type de bois (sapin, MDF, hêtre, sipo, chêne, bois mélaminé) générées au cours de différentes opérations (comme le ponçage et le sciage), et ceci dans une chambre expérimentale et dans des conditions contrôlées. Ensuite, pour l'étude de terrain, nous avons suivi, dans le cadre de leur activité professionnelle, 31 travailleurs de sexe masculin (travailleurs du bois et ébenistes) exposés aux poussières de bois pendant deux jours de travail consécutifs. Nous avons également recruté, comme groupe de contrôle, 19 travailleurs non exposés. Pour effectuer une biosurveillance, nous avons collecté des échantillons de sang et des échantillons de cellules nasales et buccales pour chacun des participants. Ces derniers ont également rempli un questionnaire comprenant des données démographiques, ainsi que sur leur style de vie et sur leur exposition professionnelle. Pour les travailleurs du bois, un échantillonnage individuel de poussière a été effectué sur chaque sujet à l'aide d'une cassette fermée, puis nous avons évalué leur exposition à la poussière de bois et aux HAP, respectivement par mesure gravimétrique et par Chromatographie en phase gazeuse combinée à la spectrométrie de masse. L'évaluation des dommages induits à l'ADN et aux chromosomes (génotoxicité) a été, elle, effectuée à l'aide du test des micronoyaux (MN) sur les cellules nasales et buccales et à l'aide du test des comètes sur les échantillons de sang. Nos résultats montrent dans la poussière de la totalité des 6 types de bois étudiés la présence de HAP (dont certains sont cancérogènes). Des différences notoires dans les concentrations ont été néanmoins constatées en fonction du matériau étudié : les concentrations allant de 0,24 ppm pour la poussière de MDF à 7.95 ppm pour le mélaminé. Nos résultats montrent également que les travailleurs ont été exposés individuellement à de faibles concentrations de HAP (de 37,5 à 119,8 ng m-3) durant les opérations de travail du bois, alors que les concentrations de poussières inhalables étaient relativement élevés (moyenne géométrique de 2,8 mg m-3). En ce qui concerne la génotoxicité, les travailleurs exposés à la poussière de bois présentent une fréquence significativement plus élevée en MN dans les cellules nasales et buccales que les travailleurs du groupe témoin : un odds ratio de 3.1 a été obtenu pour les cellules nasales (IC 95% : de 1.8 à 5.1) et un odds ratio de 1,8 pour les cellules buccales (IC 95% : de 1.3 à 2.4). En outre, le test des comètes a montré que les travailleurs qui ont déclaré être exposés aux poussières de MDF et/ou de mélaminé avaient des dommages à l'ADN significativement plus élevés que les deux travailleurs exposés à la poussière de bois naturel (sapin, épicéa, hêtre, chêne) et que les travailleurs du groupe témoin (p <.01). Enfin, la fréquence des MN dans les cellules nasales et buccales augmentent avec les années d'exposition aux poussières de bois. Par contre, il n'y a pas de relation dose-réponse concernant la génotoxicité due à l'exposition journalière à la poussière et aux HAP. Cette étude montre qu'une exposition aux HAP eu bien lieu lors des opérations de travail du bois. Les travailleurs exposés aux poussières de bois, et donc aux HAP, courent un risque plus élevé (génotoxicité) par rapport au groupe témoin. Étant donné que certains des HAP détectés sont reconnus potentiellement cancérogènes, il est envisageable que les HAP générés au cours du travail sur les matériaux de bois sont un des agents responsables de la génotoxicité de la poussière de bois et du risque élevé de SNC observé chez les travailleurs du secteur. Etant donné la corrélation entre augmentation de la fréquence des MN, le test des micronoyaux dans les cellules nasales et buccales constitue sans conteste un futur outil pour la biosurveillance et pour la détection précoce du risque de SNC chez les travailleurs. - Exposures to wood dust have been associated with an elevated risk of adenocarcinomas of the Dasal cavity and the paranasal sinuses (sinonasal cancer or SNC) among wood workers. Wood dust is recognized as a human carcinogen by the International Agency for Research on Cancer. However, the specific cancer causative agent(s) and the mechanism(s) behind wood dust related carcinogenesis remains unknown. One possible explanation is a co-exposure to wood dust and polycyclic aromatic hydrocarbons (PAH), the latter being carcinogenic. In addition, wood workers are not only exposed to natural wood but also to wood finishes and composite woods such as wood melamine and medium density fiber (MDF) boards during the manipulation with power tools. The heat produced by the use of power tools can cause the generation of PAH from wood materials. The main objectives of the present thesis are to: (1) quantify possible PAH concentrations in wood dust generated during various common woodworking operations using different wood materials; (2) quantify personal wood dust concentrations and PAH exposures among wood workers; and (3) assess genotoxic effects (i.e., DNA and chromosomal damage) of wood dust and PAH exposure in wood workers. This thesis is composed by a laboratory study (objective 1) and a field study (objectives 2 and 3). In the laboratory study we collected wood dust from different wood materials (fir, MDF, beech, mahagany, oak, and wood melamine) generated during different wood operations (e.g., sanding and sawing) in an experimental chamber under controlled conditions. In the following field study, we monitored 31 male wood workers (furniture and construction workers) exposed to wood dust during their professional activity for two consecutive work shifts. Additionally, we recruited 19 non exposed workers as a control group. We collected from each participant blood samples, and nasal and buccal cell samples. They answered a questionnaire including demographic and life-style data and occupational exposure (current and past). Personal wood dust samples were collected using a closed-face cassette. We used gravimetrie analysis to determine the personal wood dust concentrations and capillary gas chromatography - mass spectrometry analysis to determine PAH concentrations. Genotoxicity was assessed with the micronucleus (MN) assay for nasal and buccal cells and with the comet assay for blood samples. Our results show that PAH (some of them carcinogenic) were present in dust from all six wood materials tested, yet at different concentrations depending on the material. The highest concentration was found in dust from wood melamine (7.95 ppm) and the lowest in MDF (0.24 ppm). Our results also show that workers were individually exposed to low concentrations of PAHs (37.5-119.8 ng m"3) during wood working operations, whereas the concentrations of inhalable dust were relatively high (geometric mean 2.8 mg m"3). Concerning the genotoxicity, wood workers had a significantly higher MN frequency in nasal and buccal cells than the workers in the control group (odds ratio for nasal cells 3.1 (95%CI 1.8-5.1) and buccal cells 1.8 (95%CI 1.3-2.4)). Furthermore, the comet assay showed that workers who reported to be exposed to dust from wooden boards (MDF and wood melamine) had significantly higher DNA damage than both the workers exposed to natural woods (fir, spruce, beech, oak) and the workers in the control group (p < 0.01). Finally, MN frequency in nasal and buccal cells increased with increasing years of exposure to wood dust. However, there was no genotoxic dose-response relationship with the per present day wood dust and PAH exposure. This study shows that PAH exposure occurred during wood working operations. Workers exposed to wood dust, and thus to PAH, had a higher risk for genotoxicity compared to the control group. Since some of the detected PAH are potentially carcinogenic, PAH generated from operations on wood materials may be one of the causative agents for the observed increased genotoxicity in wood workers. Since increased genotoxicity is manifested in an increased MN frequency, the MN assay in nasal and buccal cells may become a relevant biomonitoring tool in the future for early detection of SNC risk.