Examining potential modes of action of Styrene inhalation on lung and liver in male C57Bl/6 mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE75159 | GEO | 2016/11/30
SECONDARY ACCESSION(S): PRJNA302652
REPOSITORIES: GEO
Similar Datasets
Project description:Examining potential modes of action of Styrene inhalation on lung and liver in male C57Bl/6 mice
| PRJNA302652 | ENA
Project description:This data set is #2 of three generated as part of a coordinated series of experiments to examine potential modes of action of Styrene inhalation on lung and liver in male C57Bl/6 mice. Styrene causes increased lung tumors in mice, but not in rats. Mouse lung tumors were found mostly at the conclusion of a life-time (104 weeks for males) exposure study and most were benign. Styrene is largely negative in genotoxicity assays. Styrene metabolism by CYP2F2 produced a different metabolite pattern in mouse lung than in liver or in rats or humans. The purpose of this study was to use genomic analyses to further investigate potential modes of action (MoA) of styrene in mice, using a total of three genomic data sets. Dataset #1 exposed C57BL/6 wild-type (WT), CYP2F2 knockout (-/-; KO) and CYP2F21 humanized (2F2-KO + 2F1,2A13,2B6-transgenic, TG) male mice to 0, 40 or 120 ppm styrene at 6 hr/day 5 days/wk for 1 or 4 wk. Lungs were analyzed by whole genome microarrays for each strain at each dose. The second part of the study examined a broader dose response and short term exposure. Male wild type C57Bl/6 mice were exposed to 6 inhalation concentrations of styrene: 0, 1, 5, 10, 20, 40, and 120 ppm for a single 6 hour exposure. This was intended to gain dose-response data at low-observed-adverse-effect-levels (LOAELs) of styrene (≥ 20 ppm) and at no-observed-adverse-effect-levels (NOAELs) of styrene (< 20 ppm). Dataset #2 examined lung gene expression, while dataset #3 examined liver gene expression data from the same animals.
2016-11-30 | GSE75157 | GEO
Project description:This data set is #3 of three generated as part of a coordinated series of experiments to examine potential modes of action of Styrene inhalation on lung and liver in male C57Bl/6 mice. Styrene causes increased lung tumors in mice, but not in rats. Mouse lung tumors were found mostly at the conclusion of a life-time (104 weeks for males) exposure study and most were benign. Styrene is largely negative in genotoxicity assays. Styrene metabolism by CYP2F2 produced a different metabolite pattern in mouse lung than in liver or in rats or humans. The purpose of this study was to use genomic analyses to further investigate potential modes of action (MoA) of styrene in mice, using a total of three genomic data sets. Dataset #1 exposed C57BL/6 wild-type (WT), CYP2F2 knockout (-/-; KO) and CYP2F21 humanized (2F2-KO + 2F1,2A13,2B6-transgenic, TG) male mice to 0, 40 or 120 ppm styrene at 6 hr/day 5 days/wk for 1 or 4 wk. Lungs were analyzed by whole genome microarrays for each strain at each dose. The second part of the study examined a broader dose response and short term exposure. Male wild type C57Bl/6 mice were exposed to 6 inhalation concentrations of styrene: 0, 1, 5, 10, 20, 40, and 120 ppm for a single 6 hour exposure. This was intended to gain dose-response data at low-observed-adverse-effect-levels (LOAELs) of styrene (≥ 20 ppm) and at no-observed-adverse-effect-levels (NOAELs) of styrene (< 20 ppm). Dataset #2 examined lung gene expression, while dataset #3 examined liver gene expression data from the same animals.
2016-11-30 | GSE75158 | GEO
Project description:Lung gene expression after long-term (26 weeks, 52 weeks, 78 weeks & 104 weeks) styrene inhalation exposure at a single concentration (120ppm) in three strains of C57BL/6 mice -- wild-type (WT), CYP2F2 knockout (KO), and CYP2F1 humanized (TG) mice, and CD-1 mice. These data examine transcriptomic changes in lung tissue after long-term styrene inhalation in male C57Bl/6 and CD-1 mice. Styrene causes increased lung tumors in mice, but not in rats. Mouse lung tumors were found mostly at the conclusion of a life-time (104 weeks for males) exposure study and most were benign. Styrene is largely negative in genotoxicity assays. Styrene metabolism by CYP2F2 produced a different metabolite pattern in mouse lung than in liver or in rats or humans. The purpose of this study was to use genomic analyses to further investigate potential modes of action (MoA) of styrene in mice after long-term exposure to styrene. Mice strains exposed were C57BL/6 wild-type (WT), CYP2F2 knockout (-/-; KO) and CYP2F21 humanized transgenic (2F2-KO + 2F1,2A13,2B6-transgenic, TG), and CD-1 male mice using 120 ppm styrene at 6 hr/day 5 days/wk for 26, 52, 78 and 104 weeks. Lungs were analyzed by Affymetrix whole genome microarrays for each strain relative to sample time-specific vehicle controls for each strain.
2018-03-08 | GSE98470 | GEO
Project description:Styrene causes increased lung tumors in mice, but not in rats. Mouse lung tumors were found mostly at the conclusion of a life-time (104 weeks for males) exposure study and most were benign. Styrene is largely negative in genotoxicity assays. Styrene metabolism by CYP2F2 produced a different metabolite pattern in mouse lung than in liver or in rats or humans. The purpose of this study was to use genomic analyses to further investigate potential modes of action (MoA) of styrene in mice. Lungs were analyzed by whole genome microarrays for each strain at each dose. Male CD-1 mice were exposed to 6 inhalation concentrations of styrene: 0, 1, 5, 10, 20, 40, and 120 ppm for a single 6 hour exposure. This was intended to gain dose-response data at low-observed-adverse-effect-levels (LOAELs) of styrene (≥ 20 ppm) and at no-observed-adverse-effect-levels (NOAELs) of styrene (< 20 ppm) for comparison with gene expression from similar Styrene inhalation exposures in a second strain of mice (C57Bl/6). Affymetrix control probes (AFFX-prefix, 104 probes) have been excluded from the data matrix.
2018-05-18 | GSE108967 | GEO
Project description: Not available
| S-EPMC2967389 | biostudies-literature
Project description:5-day styrene inhalation dose response in CD-1 mice (lung)
| PRJNA429256 | ENA
Project description:The alarming rise of antimicrobial resistance in Mycobacterium tuberculosis coupled with the shortage of new antibiotics has made tuberculosis (TB) control a global health priority. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the growth of multi-drug resistant isolates of M. tuberculosis. Repurposing NSAIDs, with known clinical properties and safety records, offers a direct route to clinical trials. Therefore we investigated the novel mechanisms of anti-mycobacterial action of the NSAID, carprofen. Integrative molecular and microbiological approaches revealed that carprofen, a bactericidal drug, inhibited bacterial drug efflux mechanisms. In addition, carprofen restricted mycobacterial biofilm-like growth, highlighting the requirement of efflux-mediated communicative systems for the formation of biofilms. Transcriptome profiling revealed that carprofen likely acts by inhibiting respiration through the disruption of membrane potential, which may explain why spontaneous drug-resistant mutants could not be raised due to the pleiotropic nature of carprofen’s anti-tubercular action. This immunomodulatory drug has the potential to reverse TB antimicrobial resistance by inhibiting drug efflux pumps and biofilm formation, and paves a new chemotherapeutic path for tackling tuberculosis.
2020-08-15 | E-MTAB-6191 | biostudies-arrayexpress
Project description: Not available
| S-EPMC7285019 | biostudies-literature
Project description:A 7-month inhalation study in C57BL/6 mice was conducted to evaluate long-term respiratory toxicity of e-vapor aerosols compared to cigarette smoke and to assess the impact of smoking cessation or switching to an e-vapor product after 3 months of exposure to 3R4F cigarette smoke (CS). In this study, we performed a chronic inhalation (4 h/day, 5 d/week, up to 7 months) study in C57BL/6 mice using a commercial (MarkTen®) e-vapor product and a combustible reference cigarette (3R4F) using a Switching and Cessation study design. A commercial e-vapor product (MarkTen® device [version 2.6.8]; “Test Red”) was supplied by Altria Client Services LLC (Richmond, VA, USA). The Test Red formulation was composed of aerosol formers (propylene glycol [PG] and vegetable glycerol [VG]), ~4% nicotine by weight, and flavors (non-menthol). The 3R4F commercial reference cigarettes were purchased from the University of Kentucky (Lexington, KY). HEPA filtered air at the testing facility (Battelle, West Jefferson, OH) was used as Sham Control. General procedures for animal care and housing met the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) recommendations and requirements stated in the “Guide for Care and Use of Laboratory Animals” [National Research Council (NRC)] and approved by the Institutional Animal Care and Use Committee (IACUC). Female C57BL/6 mice were received from Charles River Kingston (Stone Ridge, NY). Test atmosphere was generated from smoking machines and delivered to the mice through a nose-only exposure system. The modified Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) Reference Method 81 regimen (55/30/5: a 55 ± 0.3 mL puff volume, a puff every 30 seconds, a 5-second puff duration) was used to generate e-vapor aerosol for 130 puffs/cartridge. Mainstream smoke from 3R4F cigarette was generated using a modified Health Canada Intense regimen (55/30/2: a 55 ± 0.3 mL puff volume, a puff every 30 seconds, a 2-second puff duration, and a near-square puff profile) for 8 puffs/cigarette. Female C57BL/6 mice (~10 weeks old) were randomly assigned based on body weight to one of five exposure groups: Sham Control, 3R4F CS, Test Red, Switching, and Cessation. Mice were exposed to 3R4F CS (550 µg/L TPM) or e-vapor aerosols (Test Red; 1100 µg/L TPM) via nose-only inhalation up to 4 h/day, 5 d/week for up to 7 months. After the first 3 months of exposure, groups of 3R4F CS mice were subjected to exposures of: (1) Test Red aerosol (“Switching”) or (2) filtered air (“Cessation”), while a group of mice continued to be exposed to 3R4F CS. Here, the protein expression data for lung tissue assessed by iTRAQ®-based quantitative proteomics is reported.
2021-03-31 | PXD019918 | Pride