The Experts below are selected from a list of 1116 Experts worldwide ranked by ideXlab platform
Claude Dufour - One of the best experts on this subject based on the ideXlab platform.
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design and development of a flexible strain sensor for textile structures based on a conductive polymer composite
Sensors, 2007Co-Authors: Cedric Cochrane, Vladan Koncar, Maryline Lewandowski, Claude DufourAbstract:IEMN, Cite Scientifique, Avenue Poincare – BP 60069, 59652 Villeneuve d’Ascq, France; E-mail: claude.dufour@IEMN.Univ-Lille1.fr * Author to whom correspondence should be addressed. E-mail: vladan.koncar@ensait.fr Received: 13 March 2007 / Accepted: 17 April 2007 / Published: 18 April 2007 Abstract : The aim of this work is to develop a smart flexible sensor adapted to textile structures, able to measure their strain deformations. The sensors are “smart” because of their capacity to adapt to the specific mechanical properties of textile structures that are lightweight, highly flexible, stretchable, elastic, etc. Because of these properties, textile structures are continuously in movement and easily deformed, even under very low stresses. It is therefore important that the integration of a sensor does not modify their general behavior. The material used for the sensor is based on a thermoplastic elastomer (Evoprene)/Carbon Black Nanoparticle composite, and presents general mechanical properties strongly compatible with the textile substrate. Two preparation techniques are investigated: the conventional melt-mixing process, and the solvent process which is found to be more adapted for this particular application. The preparation procedure is fully described, namely the optimization of the process in terms of filler concentration in which the percolation theory aspects have to be considered. The sensor is then integrated on a thin, lightweight Nylon fabric, and the electromechanical characterization is performed to demonstrate the adaptability and the correct functioning of the sensor as a strain gauge on the fabric. A normalized relative resistance is defined in order to characterize the electrical response of the sensor. Finally, the influence of environmental factors, such as temperature and atmospheric humidity, on the sensor performance is investigated. The results show that the sensor’s electrical resistance is particularly affected by humidity. This behavior is discussed in terms of the sensitivity of the Carbon Black filler particles to the presence of water.
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Design and development of a flexible strain sensor for textile structures based on a conductive polymer composite
Sensors, 2007Co-Authors: Mateusz Lewandowski, Claude DufourAbstract:The aim of this work is to develop a smart flexible sensor adapted to textile structures, able to measure their strain deformations. The sensors are “smart” because of their capacity to adapt to the specific mechanical properties of textile structures that are lightweight, highly flexible, stretchable, elastic, etc. Because of these properties, textile structures are continuously in movement and easily deformed, even under very low stresses. It is therefore important that the integration of a sensor does not modify their general behavior. The material used for the sensor is based on a thermoplastic elastomer (Evoprene)/Carbon Black Nanoparticle composite, and presents general mechanical properties strongly compatible with the textile substrate. Two preparation techniques are investigated: the conventional melt-mixing process, and the solvent process which is found to be more adapted for this particular application. The preparation procedure is fully described, namely the optimization of the process in terms of filler concentration in which the percolation theory aspects have to be considered. The sensor is then integrated on a thin, lightweight Nylon fabric, and the electromechanical characterization is performed to demonstrate the adaptability and the correct functioning of the sensor as a strain gauge on the fabric. A normalized relative resistance is defined in order to characterize the electrical response of the sensor. Finally, the influence of environmental factors, such as temperature and atmospheric humidity, on the sensor performance is investigated. The results show that the sensor’s electrical resistance is particularly affected by humidity. This This behavior is discussed in terms of the sensitivity of the Carbon Black filler particles to the presence of water.
Carole L Yauk - One of the best experts on this subject based on the ideXlab platform.
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Carbon Black Nanoparticle intratracheal instillation does not alter cardiac gene expression
Cardiovascular Toxicology, 2013Co-Authors: Julie A Bourdon, Andrew Williams, Sabina Halappanavar, Ulla Vogel, Hakan Wallin, Anne T Saber, Nicklas Raun Jacobsen, Carole L YaukAbstract:Exposure to Nanoparticles has been associated with inflammation-related progression of atherosclerosis. To examine Nanoparticle-induced cardiac effects in more detail, we characterized heart gene expression profiles alongside plasma proteins associated with cardiovascular disease in C57BL/6 mice intratracheally instilled with vehicle or 0.162 mg Printex 90 Carbon Black Nanoparticles (CBNPs). Mice were killed 1, 3, and 28 days after the exposure and expression profiles were derived using DNA microarrays. Cardiac gene expression was unperturbed by CBNP exposure in two independent experiments, despite substantive changes in pulmonary and hepatic gene expression. MicroRNAs were not affected. Plasma levels of cell adhesion molecules (sE-selectin, sICAM-1, sVCAM-1) and total PAI-1 were immediately increased up to day 3, whereas Apo-A1 and Apo-E were marginally decreased on day 1. These data suggest that though adverse cardiovascular effects are likely following CBNP exposure, these effects are unlikely to be mediated by major direct effects on cardiac gene expression.
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gene expression profiling to identify potentially relevant disease outcomes and support human health risk assessment for Carbon Black Nanoparticle exposure
Toxicology, 2013Co-Authors: Julie A Bourdon, Andrew Williams, Sabina Halappanavar, Ivy Moffat, Paul A White, Ulla Vogel, Hakan Wallin, Carole L YaukAbstract:Abstract New approaches are urgently needed to evaluate potential hazards posed by exposure to nanomaterials. Gene expression profiling provides information on potential modes of action and human relevance, and tools have recently become available for pathway-based quantitative risk assessment. The objective of this study was to use toxicogenomics in the context of human health risk assessment. We explore the utility of toxicogenomics in risk assessment, using published gene expression data from C57BL/6 mice exposed to 18, 54 and 162 μg Printex 90 Carbon Black Nanoparticles (CBNP). Analysis of CBNP-perturbed pathways, networks and transcription factors revealed concomitant changes in predicted phenotypes (e.g., pulmonary inflammation and genotoxicity), that correlated with dose and time. Benchmark doses (BMDs) for apical endpoints were comparable to minimum BMDs for relevant pathway-specific expression changes. Comparison to inflammatory lung disease models (i.e., allergic airway inflammation, bacterial infection and tissue injury and fibrosis) and human disease profiles revealed that induced gene expression changes in Printex 90 exposed mice were similar to those typical for pulmonary injury and fibrosis. Very similar fibrotic pathways were perturbed in CBNP-exposed mice and human fibrosis disease models. Our synthesis demonstrates how toxicogenomic profiles may be used in human health risk assessment of Nanoparticles and constitutes an important step forward in the ultimate recognition of toxicogenomic endpoints in human health risk. As our knowledge of molecular pathways, dose–response characteristics and relevance to human disease continues to grow, we anticipate that toxicogenomics will become increasingly useful in assessing chemical toxicities and in human health risk assessment.
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Carbon Black Nanoparticle intratracheal installation results in large and sustained changes in the expression of mir 135b in mouse lung
Environmental and Molecular Mutagenesis, 2012Co-Authors: Julie A Bourdon, Andrew Williams, Sabina Halappanavar, Ulla Vogel, Hakan Wallin, Anne T Saber, Nicklas Raun Jacobsen, Petra Jackson, Karin Sorig Hougaard, Carole L YaukAbstract:MicroRNAs (miRNA) are important noncoding regulatory molecules that bind target messenger RNA (mRNA), primarily affecting their translation into protein. Because miRNAs can simultaneously target hundreds of mRNAs, subtle changes in their expression can elicit important cellular effects. Little is known about the role of miRNAs in pulmonary responses to inhaled particulate matter. We studied pulmonary global miRNA responses to Printex 90 Carbon Black Nanoparticles in (1) nonpregnant C57BL/6 female mice instilled with vehicle or a single dose of 0.162 mg and euthanized 1, 3, and 28 days post-exposure, and (2) C57BL/6Bom Tac dams instilled with vehicle or a cumulative dose of 0.268 mg (four separate instillations of vehicle or 0.067 mg Printex 90 during pregnancy) and euthanized at weaning (26–27 days postexposure). We measured similar expression profiles in both exposure scenarios, with marked increases in miR-135b and subtle changes in miR-21 and miR-146b. All three miRNAs were confirmed in nonpregnant females by RT-PCR, whereas only miR-135b was confirmed in the dams. Target analysis revealed no concomitant changes in established and predicted targets of miR-135b, miR-21, or miR-146b. Analysis of potentially perturbed pathways did not reveal changes that would suggest down-stream miRNA effects. The reasons for the lack of association between miRNA and transcript profiles may be related to the complexity of miRNA function and fate, or to the possibility that targets may differ from those already established or predicted in silico. We hypothesize that changes in the expression of these miRNAs may be associated with resolution of pulmonary inflammation, but future work will be necessary to precisely identify specific targets of these miRNAs in lungs. Environ. Mol. Mutagen., 2012. © 2012 Wiley Periodicals, Inc.
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Carbon Black Nanoparticle instillation induces sustained inflammation and genotoxicity in mouse lung and liver
Particle and Fibre Toxicology, 2012Co-Authors: Julie A Bourdon, Hakan Wallin, Anne T Saber, Nicklas R Jacobsen, Keld A Jensen, Anne M Madsen, Jacob S Lamson, Peter Møller, Steffen Loft, Carole L YaukAbstract:Background Widespread occupational exposure to Carbon Black Nanoparticles (CBNPs) raises concerns over their safety. CBNPs are genotoxic in vitro but less is known about their genotoxicity in various organs in vivo . Methods We investigated inflammatory and acute phase responses, DNA strand breaks (SB) and oxidatively damaged DNA in C57BL/6 mice 1, 3 and 28 days after a single instillation of 0.018, 0.054 or 0.162 mg Printex 90 CBNPs, alongside sham controls. Bronchoalveolar lavage (BAL) fluid was analyzed for cellular composition. SB in BAL cells, whole lung and liver were assessed using the alkaline comet assay. Formamidopyrimidine DNA glycosylase (FPG) sensitive sites were assessed as an indicator of oxidatively damaged DNA. Pulmonary and hepatic acute phase response was evaluated by Saa3 mRNA real-time quantitative PCR. Results Inflammation was strongest 1 and 3 days post-exposure, and remained elevated for the two highest doses (i.e., 0.054 and 0.162 mg) 28 days post-exposure (P < 0.001). SB were detected in lung at all doses on post-exposure day 1 (P < 0.001) and remained elevated at the two highest doses until day 28 (P < 0.05). BAL cell DNA SB were elevated relative to controls at least at the highest dose on all post-exposure days (P < 0.05). The level of FPG sensitive sites in lung was increased throughout with significant increases occurring on post-exposure days 1 and 3, in comparison to controls (P < 0.001-0.05). SB in liver were detected on post-exposure days 1 (P < 0.001) and 28 (P < 0.001). Polymorphonuclear (PMN) cell counts in BAL correlated strongly with FPG sensitive sites in lung (r = 0.88, P < 0.001), whereas no such correlation was observed with SB (r = 0.52, P = 0.08). CBNP increased the expression of Saa3 mRNA in lung tissue on day 1 (all doses), 3 (all doses) and 28 (0.054 and 0.162 mg), but not in liver. Conclusions Deposition of CBNPs in lung induces inflammatory and genotoxic effects in mouse lung that persist considerably after the initial exposure. Our results demonstrate that CBNPs may cause genotoxicity both in the primary exposed tissue, lung and BAL cells, and in a secondary tissue, the liver.
Flavio Della Pelle - One of the best experts on this subject based on the ideXlab platform.
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press printed conductive Carbon Black Nanoparticle films for molecular detection at the microscale
Chemistry: A European Journal, 2016Co-Authors: Flavio Della Pelle, L Vazquez, Michele Del Carlo, Manuel Sergi, Dario Compagnone, Alberto EscarpaAbstract:Carbon Black Nanoparticle (CBNP) press-transferred film-based transducers for the molecular detection at the microscale level were proposed for the first time. Current-sensing atomic force microscopy (CS-AFM) revealed that the CBNP films were effectively press-transferred, retaining their good conductivity. A significant correlation between the morphology and the resistance was observed. The highest resistance was localized at the top of the press-transferred film protrusions, whereas low values are usually obtained at the deep crevices or grooves. The amount of press-transferred CBNPs is the key parameter to obtain films with improved conductivity, which is in good agreement with the electrochemical response. In addition, the conductivity of such optimum films was not only Ohmic; in fact, tunneling/hopping contributions were observed, as assessed by CS-AFM. The CBNP films acted as exclusive electrochemical transducers as evidenced by using two classes of molecules, that is, neurotransmitters and environmental organic contaminants. These results revealed the potential of these CBNP press-transferred films for providing new options in microfluidics and other related micro- and nanochemistry applications.
Masakazu Umezawa - One of the best experts on this subject based on the ideXlab platform.
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dysregulation of major functional genes in frontal cortex by maternal exposure to Carbon Black Nanoparticle is not ameliorated by ascorbic acid pretreatment
Science of The Total Environment, 2018Co-Authors: Atsuto Onoda, Ken Takeda, Masakazu UmezawaAbstract:Recent cohort studies have revealed that perinatal exposure to particulate air pollution, including Carbon-based Nanoparticles, increases the risk of brain disorders. Although developmental neurotoxicity is currently a major issue in the toxicology of Nanoparticles, critical information for understanding the mechanisms underlying the developmental neurotoxicity of airway exposure to Carbon Black Nanoparticle (CB-NP) is still lacking. In order to investigate these mechanisms, we comprehensively analyzed fluctuations in the gene expression profile of the frontal cortex of offspring mice exposed maternally to CB-NP, using microarray analysis combined with Gene Ontology information. We also analyzed differences in the enriched function of genes dysregulated by maternal CB-NP exposure with and without ascorbic acid pretreatment to refine specific alterations in gene expression induced by CB-NP. Total of 652 and 775 genes were dysregulated by CB-NP in the frontal cortex of 6- and 12-week-old offspring mice, respectively. Among the genes dysregulated by CB-NP, those related to extracellular matrix structural constituent, cellular response to interferon-beta, muscle organ development, and cysteine-type endopeptidase inhibitor activity were ameliorated by ascorbic acid pretreatment. A large proportion of the dysregulated genes, categorized in hemostasis, growth factor, chemotaxis, cell proliferation, blood vessel, and dopaminergic neurotransmission, were, however, not ameliorated by ascorbic acid pretreatment. The lack of effects of ascorbic acid on the dysregulation of genes following maternal CB-NP exposure suggests that the contribution of oxidative stress to the effects of CB-NP on these biological functions, i.e., cell migration and proliferation, blood vessel maintenance, and dopaminergic neuron system, may be limited. At least, ascorbic acid pretreatment is hardly likely to be able to protect the brain of offspring from developmental neurotoxicity of CB-NP. The present study provides insight into the mechanisms underlying developmental neurotoxicity following maternal Nanoparticle exposure.
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dose dependent induction of astrocyte activation and reactive astrogliosis in mouse brain following maternal exposure to Carbon Black Nanoparticle
Particle and Fibre Toxicology, 2017Co-Authors: Atsuto Onoda, Ken Takeda, Masakazu UmezawaAbstract:Recent studies indicate that maternal exposure to ambient ultrafine particles and Nanoparticles has adverse effects of on the central nervous system. Quantitative dose–response data is required to better understand the developmental neurotoxicity of Nanoparticles. The present study investigated dose-dependent effects of maternal exposure to Carbon Black Nanoparticle (CB-NP) on astrocyte in the brains of mouse offspring. A CB-NP suspension (2.9, 15, or 73 μg/kg) was intranasally administered to pregnant ICR mice on gestational days 5 and 9. Cerebral cortex samples were collected from 6-week-old offspring and examined by Western blotting, immunostaining, microarray analysis, and quantitative reverse transcriptase-polymerase chain reaction. Placentae were collected from pregnant dams on gestational day 13 and examined by microarray analysis. Maternal exposure to CB-NP induced a dose-dependent increase in glial fibrillary acidic protein (GFAP) expression in the cerebral cortex; this increase was particularly observed in astrocytic end-feet attached to denatured perivascular macrophages. Moreover, maternal CB-NP exposure dose-dependently increased aquaporin-4 expression in the brain parenchyma region around blood vessels. The changes in the expression profiles of GFAP and Aqp4 in offspring after maternal CB-NP exposure were similar to those observed in mice of a more advanced age. The expression levels of mRNAs associated with angiogenesis, cell migration, proliferation, chemotaxis, and growth factor production were also altered in the cerebral cortex of offspring after maternal CB-NP exposure. Differentially expressed genes in placental tissues after CB-NP exposure did not populate any specific gene ontology category. Maternal CB-NP exposure induced long-term activation of astrocytes resulting in reactive astrogliosis in the brains of young mice. Our observations suggest a potentially increased risk of the onset of age-related neurodegenerative diseases by maternal NP exposure. In this study, we report for the first time a quantitative dose–response relationship between maternal NP exposure and phenotypic changes in the central nervous system of the offspring. Moreover, our findings indicate that cortical GFAP and Aqp4 are useful biomarkers that can be employed in further studies aiming to elucidate the underlying mechanism of Nanoparticle-mediated developmental neurotoxicity.
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Carbon Black Nanoparticle exposure during middle and late fetal development induces immune activation in male offspring mice
Toxicology, 2015Co-Authors: Ryuhei Shimizu, Ken Takeda, Atsuto Onoda, Yasser S Elsayed, Masakazu UmezawaAbstract:Increasing exposure to Nanoparticles (NPs) has raised concerns regarding their health and safety profiles in humans and animals, especially in developing organisms, which may display increased sensitivity to NP toxicity. The present study examined the effects of gestational exposure to Carbon Black NP (CB-NP) on the development of the offspring immune system. Pregnant mice were exposed to CB-NP (95μg/kg body weight) by intranasal instillation on gestational days 9 and 15. The thymus and spleen were collected from their offspring mice on postnatal day (PND) 1, 3 and 5. Thymocyte and splenocyte phenotypes were examined by determining the expression of cell-surface molecules using flow cytometry. Gene expression in the thymus and spleen was examined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Prenatal exposure to CB-NP increased total thymocytes and their immunophenotypes (CD4(-)CD8(-) and CD4(+)CD8(+) cells). It also induced an increase in total lymphocytes, and CD4(-)CD8(-), particularly CD3(-)B220(-)cells, at PND 5 in the spleen of newborn male offspring, reflecting the stimulation of immature splenocytes. Furthermore, mRNA expression of genes related to the induction of peripheral tolerance (i.e. thymic Traf6) was upregulated. These data suggest that respiratory exposure to CB-NP during middle and late gestation may have allergic or inflammatory effects in male offspring, and may provide initial information on the potential developmental immunotoxicity of Nanoparticles.
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effect of maternal exposure to Carbon Black Nanoparticle during early gestation on the splenic phenotype of neonatal mouse
Journal of Toxicological Sciences, 2014Co-Authors: Ryuhei Shimizu, Masakazu Umezawa, Saki Okamoto, Atsuto Onoda, Mariko Uchiyama, Ken Tachibana, Shiho Watanabe, Shuhei Ogawa, Ryo Abe, Ken TakedaAbstract:Maternal exposure to environmental factors is implicated as a major factor in the development of the immune system in newborns. Newborns are more susceptible to microbial infection because their immune system is immature. Development of lymphocytes reflects an innate program of lymphocyte proliferation. The aim of this study was to investigate the effects of maternal exposure to Carbon Black Nanoparticle (CB-NP) during early gestation on the development of lymphoid tissues in infantile mice. Pregnant ICR mice were treated with a suspension of CB-NP (95 μg kg(-1) time(-1)) by intranasal instillation on gestational day 5 and 9. Spleen tissues were collected from offspring mice at 1, 3, 5, and 14 days postpartum. Splenocyte phenotypes were examined by investigating the pattern of surface molecules using flow cytometry. Gene expression in the spleen was examined by quantitative RT-PCR. CD3(+) (T), CD4(+) and CD8(+) cells were decreased in the spleen of 1-5-day-old offspring in the treated group. Expression level of Il15 was significantly increased in the spleen of newborn male offspring, and Ccr7 and Ccl19 were increased in the spleen of female offspring in the CB-NP group. Splenic mRNA change profiles by CBNP were similar between male and female offspring. This article concluded that exposure of pregnant mothers to CB-NP partially suppressed the development of the immune system of offspring mice. The decrease in splenic T cells in the treated group recovered at 14 days after birth. This is the first report of developmental effect of Nanoparticle on the lymphatic phenotype.
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maternal exposure to Carbon Black Nanoparticle increases collagen type viii expression in the kidney of offspring
Journal of Toxicological Sciences, 2011Co-Authors: Masakazu Umezawa, Sayaka Kudo, Shinya Yanagita, Yusuke Shinkai, Rikio Niki, Taito Oyabu, Ken Takeda, Tomomi Ihara, Masao SugamataAbstract:The potential health risks of inhaling nanomaterials are of great concern because of their high specific activity and their unique property of translocation. Earlier studies showed that exposure to Nanoparticles through the airway affects both respiratory and extrapulmonary organs. When pregnant mice were exposed to Nanoparticles, the respiratory system, the central nervous system and the reproductive system of their offspring were affected. The aim of this study was to assess the effect of maternal exposure to Nanoparticles on the offspring, particularly on the kidney. Pregnant ICR mice were exposed to a total of 100 µg of Carbon Black Nanoparticle on the fifth and the ninth days of pregnancy. Samples of blood and kidney tissue were collected from 3-week-old and 12-week-old male offspring mice. Collagen expression was examined by quantitative RT-PCR and immunohistochemistry. Serum levels of creatinine and blood urea nitrogen were examined. Exposure of pregnant ICR mice to Carbon Black resulted in increased expression of Collagen, type VIII, a1 (Col8a1) in the tubular cells in the kidney of 12-week-old offspring mice but not in 3-week-old ones. The levels of serum creatinine and blood urea nitrogen, indices of renal function, were not different between the groups. These observations were similar to those of tubulointerstitial fibrosis in diabetic nephropathy. These results suggest that maternal exposure to Carbon Black Nanoparticle induces renal abnormalities similar to tubulointerstitial fibrosis in diabetic nephropathy are induced in the kidney of offspring.
Julie A Bourdon - One of the best experts on this subject based on the ideXlab platform.
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Carbon Black Nanoparticle intratracheal instillation does not alter cardiac gene expression
Cardiovascular Toxicology, 2013Co-Authors: Julie A Bourdon, Andrew Williams, Sabina Halappanavar, Ulla Vogel, Hakan Wallin, Anne T Saber, Nicklas Raun Jacobsen, Carole L YaukAbstract:Exposure to Nanoparticles has been associated with inflammation-related progression of atherosclerosis. To examine Nanoparticle-induced cardiac effects in more detail, we characterized heart gene expression profiles alongside plasma proteins associated with cardiovascular disease in C57BL/6 mice intratracheally instilled with vehicle or 0.162 mg Printex 90 Carbon Black Nanoparticles (CBNPs). Mice were killed 1, 3, and 28 days after the exposure and expression profiles were derived using DNA microarrays. Cardiac gene expression was unperturbed by CBNP exposure in two independent experiments, despite substantive changes in pulmonary and hepatic gene expression. MicroRNAs were not affected. Plasma levels of cell adhesion molecules (sE-selectin, sICAM-1, sVCAM-1) and total PAI-1 were immediately increased up to day 3, whereas Apo-A1 and Apo-E were marginally decreased on day 1. These data suggest that though adverse cardiovascular effects are likely following CBNP exposure, these effects are unlikely to be mediated by major direct effects on cardiac gene expression.
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gene expression profiling to identify potentially relevant disease outcomes and support human health risk assessment for Carbon Black Nanoparticle exposure
Toxicology, 2013Co-Authors: Julie A Bourdon, Andrew Williams, Sabina Halappanavar, Ivy Moffat, Paul A White, Ulla Vogel, Hakan Wallin, Carole L YaukAbstract:Abstract New approaches are urgently needed to evaluate potential hazards posed by exposure to nanomaterials. Gene expression profiling provides information on potential modes of action and human relevance, and tools have recently become available for pathway-based quantitative risk assessment. The objective of this study was to use toxicogenomics in the context of human health risk assessment. We explore the utility of toxicogenomics in risk assessment, using published gene expression data from C57BL/6 mice exposed to 18, 54 and 162 μg Printex 90 Carbon Black Nanoparticles (CBNP). Analysis of CBNP-perturbed pathways, networks and transcription factors revealed concomitant changes in predicted phenotypes (e.g., pulmonary inflammation and genotoxicity), that correlated with dose and time. Benchmark doses (BMDs) for apical endpoints were comparable to minimum BMDs for relevant pathway-specific expression changes. Comparison to inflammatory lung disease models (i.e., allergic airway inflammation, bacterial infection and tissue injury and fibrosis) and human disease profiles revealed that induced gene expression changes in Printex 90 exposed mice were similar to those typical for pulmonary injury and fibrosis. Very similar fibrotic pathways were perturbed in CBNP-exposed mice and human fibrosis disease models. Our synthesis demonstrates how toxicogenomic profiles may be used in human health risk assessment of Nanoparticles and constitutes an important step forward in the ultimate recognition of toxicogenomic endpoints in human health risk. As our knowledge of molecular pathways, dose–response characteristics and relevance to human disease continues to grow, we anticipate that toxicogenomics will become increasingly useful in assessing chemical toxicities and in human health risk assessment.
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Carbon Black Nanoparticle intratracheal installation results in large and sustained changes in the expression of mir 135b in mouse lung
Environmental and Molecular Mutagenesis, 2012Co-Authors: Julie A Bourdon, Andrew Williams, Sabina Halappanavar, Ulla Vogel, Hakan Wallin, Anne T Saber, Nicklas Raun Jacobsen, Petra Jackson, Karin Sorig Hougaard, Carole L YaukAbstract:MicroRNAs (miRNA) are important noncoding regulatory molecules that bind target messenger RNA (mRNA), primarily affecting their translation into protein. Because miRNAs can simultaneously target hundreds of mRNAs, subtle changes in their expression can elicit important cellular effects. Little is known about the role of miRNAs in pulmonary responses to inhaled particulate matter. We studied pulmonary global miRNA responses to Printex 90 Carbon Black Nanoparticles in (1) nonpregnant C57BL/6 female mice instilled with vehicle or a single dose of 0.162 mg and euthanized 1, 3, and 28 days post-exposure, and (2) C57BL/6Bom Tac dams instilled with vehicle or a cumulative dose of 0.268 mg (four separate instillations of vehicle or 0.067 mg Printex 90 during pregnancy) and euthanized at weaning (26–27 days postexposure). We measured similar expression profiles in both exposure scenarios, with marked increases in miR-135b and subtle changes in miR-21 and miR-146b. All three miRNAs were confirmed in nonpregnant females by RT-PCR, whereas only miR-135b was confirmed in the dams. Target analysis revealed no concomitant changes in established and predicted targets of miR-135b, miR-21, or miR-146b. Analysis of potentially perturbed pathways did not reveal changes that would suggest down-stream miRNA effects. The reasons for the lack of association between miRNA and transcript profiles may be related to the complexity of miRNA function and fate, or to the possibility that targets may differ from those already established or predicted in silico. We hypothesize that changes in the expression of these miRNAs may be associated with resolution of pulmonary inflammation, but future work will be necessary to precisely identify specific targets of these miRNAs in lungs. Environ. Mol. Mutagen., 2012. © 2012 Wiley Periodicals, Inc.
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Carbon Black Nanoparticle instillation induces sustained inflammation and genotoxicity in mouse lung and liver
Particle and Fibre Toxicology, 2012Co-Authors: Julie A Bourdon, Hakan Wallin, Anne T Saber, Nicklas R Jacobsen, Keld A Jensen, Anne M Madsen, Jacob S Lamson, Peter Møller, Steffen Loft, Carole L YaukAbstract:Background Widespread occupational exposure to Carbon Black Nanoparticles (CBNPs) raises concerns over their safety. CBNPs are genotoxic in vitro but less is known about their genotoxicity in various organs in vivo . Methods We investigated inflammatory and acute phase responses, DNA strand breaks (SB) and oxidatively damaged DNA in C57BL/6 mice 1, 3 and 28 days after a single instillation of 0.018, 0.054 or 0.162 mg Printex 90 CBNPs, alongside sham controls. Bronchoalveolar lavage (BAL) fluid was analyzed for cellular composition. SB in BAL cells, whole lung and liver were assessed using the alkaline comet assay. Formamidopyrimidine DNA glycosylase (FPG) sensitive sites were assessed as an indicator of oxidatively damaged DNA. Pulmonary and hepatic acute phase response was evaluated by Saa3 mRNA real-time quantitative PCR. Results Inflammation was strongest 1 and 3 days post-exposure, and remained elevated for the two highest doses (i.e., 0.054 and 0.162 mg) 28 days post-exposure (P < 0.001). SB were detected in lung at all doses on post-exposure day 1 (P < 0.001) and remained elevated at the two highest doses until day 28 (P < 0.05). BAL cell DNA SB were elevated relative to controls at least at the highest dose on all post-exposure days (P < 0.05). The level of FPG sensitive sites in lung was increased throughout with significant increases occurring on post-exposure days 1 and 3, in comparison to controls (P < 0.001-0.05). SB in liver were detected on post-exposure days 1 (P < 0.001) and 28 (P < 0.001). Polymorphonuclear (PMN) cell counts in BAL correlated strongly with FPG sensitive sites in lung (r = 0.88, P < 0.001), whereas no such correlation was observed with SB (r = 0.52, P = 0.08). CBNP increased the expression of Saa3 mRNA in lung tissue on day 1 (all doses), 3 (all doses) and 28 (0.054 and 0.162 mg), but not in liver. Conclusions Deposition of CBNPs in lung induces inflammatory and genotoxic effects in mouse lung that persist considerably after the initial exposure. Our results demonstrate that CBNPs may cause genotoxicity both in the primary exposed tissue, lung and BAL cells, and in a secondary tissue, the liver.