Lungs of mice exposed to subtoxic doses of nano-titanium dioxide particles by inhalation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE19487 | GEO | 2010/12/13
SECONDARY ACCESSION(S): PRJNA122277
REPOSITORIES: GEO
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Project description:Acute phase reactants serum amyloid A-1, 3 and micro RNA-135b, -449a, and -1 are induced in lungs of mice exposed to subtoxic doses of nano-titanium dioxide particles by inhalation In the present study we investigate pulmonary mRNA and miRNA profiles of mice exposed to subtoxic dose of nano-titanium dioxide particles by inhalation. We show dramatic induction of acute phase reactants, chemoattractants, immune and host defence related genes. We also demonstrate for the first time changes in miRNA profiles in the lungs in response to nanoTiO2. Keywords: Toxicology, disease state analysis, biomarkers of health effects Female C57BL/6 mice were exposed to 40 mg nanoTiO2/m3 for one hour/day for 11 consecutive days and were sacrificed 5 days following the last exposure. Left lung lobes and liver were removed and flash frozen. Total RNA was isolated from a small random part of the frozen lung and liver and was hybridized against universal mouse reference RNA to Agilent Oligo DNA microarrays (Agilent Technologies) containing 44,000 transcripts. Microarrays were normalized using a global LOWESS approach and analyzed by MAANOVA 2.0 and SAM. Microarray results were validated by real time RT-PCR. Impact of alteration in expression of select genes was further validated by analysing their total protein levels in lung tissue homogenates.
2010-12-13 | E-GEOD-19487 | biostudies-arrayexpress
Project description:Lungs of mice exposed to subtoxic doses of nano-titanium dioxide particles by inhalation
| PRJNA122277 | ENA
Project description:Our objective was to investigate epigenomic and transcriptomic changes in J774 macrophages after incubation with talc and titanium dioxide particles. This dataset comprises the results of reduced representation bisulfite sequencing (RRBS) of the J774 cell DNA 24 hours after exposure to 10 ug/well of fine-sized talc or titanium dioxide particles in vitro with or without 2 ug/mL 17-b estradiol.
2020-05-12 | GSE150322 | GEO
Project description:The toxicity and toxicogenomics of selected anatase and rutile nanoparticles (NP) and bulk titanium dioxide (TiO2) particles were evaluated in the soil nematode Caenorhabditis elegans. Results indicated that bulk or nano-TiO2 particles were slightly toxic to soil nematode C. elegans, as measured by reproduction EC50 values ranging from 4 to 32 mg/L. Whole-genome microarray results indicated that the regulation of glutathione-S-transferase gst-3, cytochrome P450 cypp33-c11, stress resistance regulator scl-1, oxidoreductase wah-1, and embryonic development pod-2 genes were significantly affected by nano-sized and bulk TiO2 particles. More specifically, it was determined that anatase particles exerted a greater effect on metabolic pathways, whereas rutile particles had a greater effect on developmental processes. The up-regulation of the pod-2 gene corroborated the phenotypic effect observed in the reproduction test. Our results demonstrated that C. elegans is a good genomic model for nano-TiO2 toxicity assessment.
2014-07-17 | GSE59470 | GEO
Project description:Pulmonary exposure to high doses of nanoparticles (NP) leads to well characterized lung toxicity in addition to long-term NP retention. However, pulmonary NP accumulation and toxicity following low dose exposures are not well described. In the present study we sought to: (1) investigate particle retention in mouse lungs following intratracheal instillation of varying doses of nano-sized titanium dioxide (nano-TiO2) and (2) determine the effects of long-term particle accumulation on pulmonary systems. Female C57BL/6 mice were exposed to rutile nano-TiO2 (primary size of 20.6 nm and surface area of 107.7 m2/g) via single intratracheal instillations of 18, 54 and 162 µg/mouse and sampled 1, 3 and 28 days post-exposure. The deposition of nano-TiO2 in the lungs was assessed using Nanoscale Hyperspectral Microscope. DNA microarrays, pathway-specific real-time RT-PCR (qPCR) and gene-specific qPCR arrays, and tissue protein analyses were employed to characterize pulmonary responses. Hyperspectral mapping showed dose-dependent retention of nano-TiO2 in the lungs up to 28 days post-exposure time. Retention did not correlate with the extent of inflammatory neutrophil influx into the lungs. DNA microarray analysis showed altered expression of approximately 3000 genes across all treatment groups (±1.3 fold; p<0.1). Several inflammatory mediators changed in a dose- and time-dependent manner at both the mRNA and protein levels. Although the low dose exposure failed to induce observable inflammation, significant changes in the expression of genes and proteins associated with inflammation were observed. Moreover, diminished (or absent) neutrophil influx in the low and medium dose groups was correlated with negative regulation of genes associated with ion homeostasis and muscle regulation. Gene expression changes for several inflammatory mediators have previously been noted in mice exposed to the same nano-TiO2 via inhalation. Our results suggest that retention of nano-TiO2 in the absence of inflammation and effective clearance can perturb calcium and ion homeostasis, and affect smooth muscle activities over time.
2013-11-01 | GSE41041 | GEO
Project description:An estimated 1% or less of the nanoparticles (NPs) deposited in lungs translocate to systemic circulation and enter other organs; however this estimation may not be accurate considering the low sensitivity of the existing in vivo NP detection methods. Moreover, the biological outcomes of such low levels of translocation are not elucidated. The objectives of the present study were to employ a Nano-scale Hyperspectral Microscope to spatially observe and spectrally profile NPs in tissues, and characterize the effects of NPs in blood, liver and heart following pulmonary deposition and subsequent translocation from lungs. Adult female C57BL/6 mice were exposed via intratracheal instillation to 18 and 162 µg per mouse of industrially relevant non-doped titanium dioxide nanoparticles (nano-TiO2). Using the Nano-scale Hyperspectral Microscope translocation to heart and liver was confirmed at both doses and to blood at the highest dose at 24 hours post-exposure time-point. The analysis of biological effects using DNA microarrays, RT-qPCR and ELISA revealed activation of complement cascade and inflammatory process in heart and specific activation of complement factor 3 in blood, potentially suggestive of activation of early innate immune response essential for particle opsonisation and clearance. The liver showed subtle response with changes in the expression of few genes associated with acute phase genes. This study establishes a direct link between particle translocation and systemic effects. An estimated 1% or less of the nanoparticles (NPs) deposited in lungs translocate to systemic circulation and enter other organs; however this estimation may not be accurate considering the low sensitivity of the existing in vivo NP detection methods. Moreover, the biological outcomes of such low levels of translocation are not elucidated. The objectives of the present study were to employ a Nano-scale Hyperspectral Microscope to spatially observe and spectrally profile NPs in tissues, and characterize the effects of NPs in blood, liver and heart following pulmonary deposition and subsequent translocation from lungs. Adult female C57BL/6 mice were exposed via intratracheal instillation to 18 and 162 µg per mouse of industrially relevant non-doped titanium dioxide nanoparticles (nano-TiO2). Using the Nano-scale Hyperspectral Microscope translocation to heart and liver was confirmed at both doses and to blood at the highest dose at 24 hours post-exposure time-point. The analysis of biological effects using DNA microarrays, RT-qPCR and ELISA revealed activation of complement cascade and inflammatory process in heart and specific activation of complement factor 3 in blood, potentially suggestive of activation of early innate immune response essential for particle opsonisation and clearance. The liver showed subtle response with changes in the expression of few genes associated with acute phase genes. This study establishes a direct link between particle translocation and systemic effects. This experiment consists of one dose of nano-TiO2 (162 ug) and one control. There are 2 time points for each treatment and control group, e.g., day 1 and day 28. Each dose or time point has 5-6 biological replicates. There are total 22 samples (arrays)
2015-03-31 | E-GEOD-56325 | biostudies-arrayexpress
Project description:An estimated 1% or less of the nanoparticles (NPs) deposited in lungs translocate to systemic circulation and enter other organs; however this estimation may not be accurate considering the low sensitivity of the existing in vivo NP detection methods. Moreover, the biological outcomes of such low levels of translocation are not elucidated. The objectives of the present study were to employ a Nano-scale Hyperspectral Microscope to spatially observe and spectrally profile NPs in tissues, and characterize the effects of NPs in blood, liver and heart following pulmonary deposition and subsequent translocation from lungs. Adult female C57BL/6 mice were exposed via intratracheal instillation to 18 and 162 µg per mouse of industrially relevant non-doped titanium dioxide nanoparticles (nano-TiO2). Using the Nano-scale Hyperspectral Microscope translocation to heart and liver was confirmed at both doses and to blood at the highest dose at 24 hours post-exposure time-point. The analysis of biological effects using DNA microarrays, RT-qPCR and ELISA revealed activation of complement cascade and inflammatory process in heart and specific activation of complement factor 3 in blood, potentially suggestive of activation of early innate immune response essential for particle opsonisation and clearance. The liver showed subtle response with changes in the expression of few genes associated with acute phase genes. This study establishes a direct link between particle translocation and systemic effects. An estimated 1% or less of the nanoparticles (NPs) deposited in lungs translocate to systemic circulation and enter other organs; however this estimation may not be accurate considering the low sensitivity of the existing in vivo NP detection methods. Moreover, the biological outcomes of such low levels of translocation are not elucidated. The objectives of the present study were to employ a Nano-scale Hyperspectral Microscope to spatially observe and spectrally profile NPs in tissues, and characterize the effects of NPs in blood, liver and heart following pulmonary deposition and subsequent translocation from lungs. Adult female C57BL/6 mice were exposed via intratracheal instillation to 18 and 162 µg per mouse of industrially relevant non-doped titanium dioxide nanoparticles (nano-TiO2). Using the Nano-scale Hyperspectral Microscope translocation to heart and liver was confirmed at both doses and to blood at the highest dose at 24 hours post-exposure time-point. The analysis of biological effects using DNA microarrays, RT-qPCR and ELISA revealed activation of complement cascade and inflammatory process in heart and specific activation of complement factor 3 in blood, potentially suggestive of activation of early innate immune response essential for particle opsonisation and clearance. The liver showed subtle response with changes in the expression of few genes associated with acute phase genes. This study establishes a direct link between particle translocation and systemic effects. This experiment consists of one dose of nano-TiO2 (162 ug) and one control. There are 2 time points for each treatment and control group, e.g., day 1 and day 28. Each dose or time point has 5-6 biological replicates. There are total 22 samples (arrays)
2015-03-31 | E-GEOD-56324 | biostudies-arrayexpress
Project description:Background: N6-methyladenosine (m6A) is the most prominent epitranscriptomic modification to RNA in eukaryotes, but it’s role in adaptive changes within the gestational environment are poorly understood. Nano titanium dioxide (TiO2) exposure is common during pregnancy, though the impact fetal progeny is not entirely understood. We propose that gestational exposure to nano-TiO2 contributes to cardiac m6A methylation in fetal offspring and indirectly contributes to mitochondrial dysfunction.
2022-08-24 | GSE211480 | GEO
Project description:Background: N6-methyladenosine (m6A) is the most prominent epitranscriptomic modification to RNA in eukaryotes, but it’s role in adaptive changes within the gestational environment are poorly understood. Nano titanium dioxide (TiO2) exposure is common during pregnancy, though the impact fetal progeny is not entirely understood. We propose that gestational exposure to nano-TiO2 contributes to cardiac m6A methylation in fetal offspring and indirectly contributes to mitochondrial dysfunction.
2022-08-24 | GSE211479 | GEO
Project description:In this work we study the pulmonary toxicological properties of titanium dioxide using molecular toxicological approache. For this, we exposed Sprague Dawley rats by inhalation. Lung samples have been collected up to 180 days after the end of exposure and transcriptomics analysis were performed.
2023-07-19 | GSE160117 | GEO