HAL du Programme national de recherche environnement-santé-travail (PNR EST)
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Human T lymphocytes bioactivate heterocyclic aromatic amines by forming DNA adducts
No full textInternational audienceHeterocyclic 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
Psychotropic drugs in mixture alter swimming behaviour of Japanese medaka (Oryzias latipes) larvae above environmental concentrations
No full textInternational audiencePsychiatric pharmaceuticals, such as anxiolytics, sedatives, hypnotics and antidepressors, are among the most prescribed active substances in the world. The occurrence of these compounds in the environment, as well as the adverse effects they can have on non-target organisms, justifies the growing concern about these emerging environmental pollutants. This study aims to analyse the effects of six psychotropic drugs, valproate, cyamemazine, citalopram, sertraline, fluoxetine and oxazepam, on the survival and locomotion of Japanese medaka Oryzias latipes larvae. Newly hatched Japanese medaka were exposed to individual compounds for 72 h, at concentrations ranging from 10 μg L−1 to 10 mg L−1. Lethal concentrations 50 % (LC50) were estimated at 840, 841 and 9,136 μg L−1 for fluoxetine, sertraline and citalopram, respectively, while other compounds did not induce any significant increase in mortality. Analysis of the swimming behaviour of larvae, including total distance moved, mobility and location, provided an estimated lowest observed effect concentration (LOEC) of 10 μg L−1 for citalopram and oxazepam, 12.2 μg L−1 for cyamemazine, 100 μg L−1 for fluoxetine, 1,000 μg L−1 for sertraline and >10,000 μg L−1 for valproate. Realistic environmental mixture of the six psychotropic compounds induced disruption of larval locomotor behaviour at concentrations about 10- to 100-fold greater than environmental concentrations
Cerebral radiofrequency exposures during adolescence : Impact on astrocytes and brain functions in healthy and pathologic rat models
No full textInternational audienceThe widespread use of mobile phones by adolescents raises concerns about possible health effects of radiofrequency electromagnetic fields (RF EMF 900 MHz) on the immature brain. Neuro-development is a period of particular sensitivity to repeated environmental challenges such as pro-inflammatory insults. Here, we used rats to assess whether astrocyte reactivity, perception, and emotionality were affected by RF EMF exposures during adolescence. We also investigated if adolescent brains were more sensitive to RF EMF exposures after neurodevelopmental inflammation. To do so, we either performed 80 μg/kg intra-peritoneal injections of lipopolysaccharides during gestation or 1.25 μg/h intra-cerebro-ventricular infusions during adolescence. From postnatal day (P)32 to 62, rats were subjected to 45 min RF EMF exposures to the brain (specific absorption rates: 0, 1.5, or 6 W/kg, 5 days/week). From P56, they were tested for perception of novelty, anxiety-like behaviors, and emotional memory. To assess astrocytic reactivity, Glial Fibrillary Acidic Protein was measured at P64. Our results did not show any neurobiological impairment in healthy and vulnerable RF EMF-exposed rats compared to their sham-exposed controls. These data did not support the hypothesis of a specific cerebral sensitivity to RF EMF of adolescents, even after a neurodevelopmental inflammation
L'exposition fœtale aux polluants alimentaires
No full textScientifiques et pouvoirs publics s’inquiètent du rôle éventuel que pourraient jouer les perturbateurs endocriniens dans l’apparition de certaines maladies chroniques, comme l’obésité et le diabète de type 2. Cette étude de faisabilité "DevPolEndo" visait justement à mettre au point un protocole pour déterminer si un mélange de polluants administré à faible dose, pouvait affecter la reproduction et le métabolisme de la descendance, et si l’obésité et l’âge de la mère constituaient des facteurs aggravants
Risk of neuroblastoma, birth-related characteristics, congenital ă malformations and perinatal exposures: A pooled analysis of the ESCALE ă and ESTELLE French studies (SFCE)
No full textInternational audienceNeuroblastoma (NB), an embryonic tumour arising from neural crest cells, ă is the most common malignancy among infants. The aetiology of NB is ă largely unknown. We conducted a pooled analysis to explore whether there ă is an association between NB and preconception and perinatal factors ă using data from two French national population-based case-control ă studies. The mothers of 357 NB cases and 1783 controls younger than 6 ă years, frequency-matched by age and gender, responded to a telephone ă interview that focused on demographic, socioeconomic and perinatal ă characteristics, childhood environment, life-style and maternal ă reproductive history. Unconditional logistic regression was used to ă estimate pooled odds ratios and 95% confidence intervals. After ă controlling for matching variables, study of origin and potential ă confounders, being born either small (OR 1.4 95% CI 1.0-2.0) or large ă (OR 1.5 95% CI 1.1-2.2) for gestational age and, among children younger ă than 18 months, having congenital malformations (OR 3.6 95% CI ă 1.3-8.9), were significantly associated with NB. Inverse associations ă were observed with breastfeeding (OR 0.7 95% CI 0.5-1.0) and maternal ă use of any supplements containing folic acid, vitamins or minerals (OR ă 0.5 95% CI 0.3-0.9) during the preconception period. Our findings ă reinforce the hypothesis that fetal growth anomalies and congenital ă malformations may be associated with an increased risk of NB. Further ă investigations are needed in order to clarify the role of folic acid ă supplementation and breastfeeding, given their potential importance in ă NB prevention
Exposition aux perturbateurs endocriniens et descendance
No full textLe projet de recherche SPEPI fait suite à des travaux ayant montré des effets délétères dans plusieurs organes et tissus de la génération non exposée issue de rats mâles exposés de la conception à l'âge adulte à plusieurs perturbateurs endocriniens, seuls ou associés à des doses pertinentes par rapport aux expositions humaines. L'hypothèse de travail est que les spermatozoïdes des mâles exposés sont le "vecteur" des anomalies observées en seconde génération - l'état des connaissances actuelles suggérant que les effets observés pourraient résulter d’une dérégulation épigénétique
A combined proteomic and targeted analysis unravels new toxic mechanisms for zinc oxide nanoparticles in macrophages
No full textInternational audienceThe cellular responses of the J774 macrophage cell line to zinc oxide and zirconium oxide nanoparticles have been studied by a comparative quantitative, protein level based proteomic approach. The most prominent results have been validated by targeted approaches. These approaches have been carried out under culture conditions that stimulate mildly the aryl hydrocarbon receptor, thereby mimicking conditions that can be encountered in vivo in complex environments. The comparative approach with two nanoparticles allows to separate the common responses, which can be attributed to the phagocytosis event per se, from the response specific to each type of nanoparticles. The zinc-specific responses are the most prominent ones and include mitochondrial proteins too, but also signaling molecules such as MyD88, proteins associated with methylglyoxal detoxification (glyoxalase 2, aldose reductase) and deoxyribonucleotide hydrolases. The in cellulo inhibition of GAPDH by zinc was also documented, representing a possible source of methylglyoxal in the cells, leading to an increase in methylglyoxal-modified DNA bases. These observations may be mechanisticall
Semi-volatile organic compounds in the particulate phase in dwellings: A nationwide survey in France
No full textInternational audienceSixty-six semi-volatile organic compounds (SVOCs)—phthalates, polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), one pyrethroid, organochlorine and organophosphorous pesticides, alkylphenols, synthetic musks, tri-n-butylphosphate and triclosan—were measured on PM10 filters collected over 7 days during a nationwide survey of 285 French dwellings, representative of nearly 25 million housing units. Thirty-five compounds were detected in more than half of the dwellings. PAHs, phthalates and triclosan were the major particle-bound SVOCs, with a median concentration greater than 1 ng m−3 for butylbenzyl phthalate (BBP) (median: 1.6 ng m−3), di(2-ethylhexyl) phthalate (DEHP) (46 ng m−3) and di-iso-nonyl phthalate (DiNP) (7.9 ng m−3), and greater than 0.1 ng m−3 for triclosan (114 pg m−3), benzo(a)anthracene (44.4 pg m−3), benzo(a)pyrene (138 pg m−3), benzo(b)fluoranthene (306 pg m−3), benzo(g,h,i)perylene (229 pg m−3), and indeno(1,2,3-c,d)pyrene (178 pg m−3). For most of the SVOCs, higher concentrations were found in the dwellings of smokers and during the heating season. The concentrations of banned SVOCs—namely, PCBs and organochlorine pesticides—were correlated. Permethrin, 4-tert-butylphenol and bisphenol-A showed no correlation with the other SVOCs and seemed to have their own specific sources. Most SVOCs were positively associated with PM10 concentration, suggesting that any factor that raises the mass of indoor airborne particles also increases the exposure to SVOCs through inhalatio
Air intérieur et maladies respiratoires chroniques de l'enfant
No full textNational audienceEn moyenne, plus de 11% des enfants âgés de 13 à 14 ans souffrent de symptômes asthmatiques dans l’ensemble de l’Europe. En France, les allergies respiratoires sont au premier rang des maladies chroniques de l’enfant. Compte-tenu du temps passé par cette population dans les espaces clos (70% à 90%), on s’interroge sur le rôle des polluants de l’air intérieur sur le développement de ces affections respiratoires
