Identification of Exposure Biomarkers for Mutagenic Carcinogens in Complex Environmental Matrices
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE19437 | GEO | 2010/12/09
SECONDARY ACCESSION(S): PRJNA122309
REPOSITORIES: GEO
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Project description:We investigated an in vitro experimental exposure model of the MutaMouse flat epithelial (FE1) cells exposed to a complex mixture of carcinogenic PAHs known as coal tar (SRM 1597a) using an Agilent 22k, oligo mouse array platform. Keywords: Toxicology, biomarkers discovery, stress response, complex mixture of carcinogens, PAHs The FE1 cells were exposed to two different sub-toxic concentrations of coal tar (SRM 1597a): 1 mg/ml and 4 mg/ml in a serum free media. After 6h exposure, the cells were washed twice with PBS and re-incubated in fresh media without coal tar. After 4h and 8h incubation, the media were collected for proteomic experiment and the cells were collected from the petri dishes for RNA extraction.
2010-12-09 | E-GEOD-19437 | biostudies-arrayexpress
Project description:The polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BaP), was compared to dibenzo[def,p]chrysene (DBC) and combinations of three environmental PAH mixtures (coal tar, diesel particulate and cigarette smoke condensate) using a two stage, FVB/N mouse skin tumor model. DBC (4 nmol) was most potent, reaching 100% tumor incidence with a shorter latency to tumor formation, less than 20 weeks of 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion compared to all other treatments. Multiplicity was 4 times greater than BaP (400 nmol). Both PAHs produced primarily papillomas followed by squamous cell carcinoma and carcinoma in situ. Diesel particulate extract (1 mg SRM 1650b; mix 1 ) did not differ from toluene controls and failed to elicit a carcinogenic response. Addition of coal tar extract (1 mg SRM 1597a; mix 2) produced a response similar to BaP. Further addition of 2 mg of cigarette smoke condensate (mix 3) did not alter the response of mix 2. PAH-DNA adducts measured in epidermis 12 h post initiation and analyzed by 32P post- labeling, did not correlate with tumor incidence. PAH dependent alteration in transcriptome of skin 12 h post initiation was assessed by microarray. Principal component analysis (sum of all treatments) of the 922 significantly altered genes (p<0.05), showed DBC and BaP to cluster distinct from PAH mixtures and each other. BaP and mixtures up-regulated phase 1 and 2 metabolizing enzymes while DBC did not. The carcinogenicity with DBC and two of the mixtures was much greater than would be predicted based on published Relative Potency Factors (RPFs). Gene expression was measured in mouse skin 12 hours after initiation with PAH carcinogens. The following initiation treatments were applied to mice (N=4 or 5 per biological replicates treatment); toluene vehicle control (200 M-NM-<l), BaP 400 nmol (100 M-NM-<g), DBC 4 nmol (1.2 M-NM-<g), or to mixtures of environmental PAH mixtures containing diesel particulate extract, coal tar extract, or cigarette smoke condensate.
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Project description:Polycyclic aromatic hydrocarbons (PAHs) are a class of hundreds of structurally similar chemicals ubiquitously present in our environment. They are created during the incomplete combustion of organic materials, such as oil, wood, tobacco, and charbroiled meat. As such, human exposure to mixtures of PAHs can occur through consumption of PAH-containing foods and water, inhalation of polluted air, or dermal contact. Several PAHs have been classified as carcinogenic to humans or probably carcinogenic to humans by the International Agency for Research on Cancer. The mice in this study were exposed to a complex mixture of PAHs - coal tar. In the present study, we sought to determine the dose-dependent changes in gene expression upon oral exposure to this PAH mixture in the lung tissue. Adult male MutaTMMouse were exposed to three doses of the coal tar or vehicle control (olive oil) for 28 days and sacrificed three days after the final exposure.
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Project description:Coal tar pitch (CTP) is a byproduct of cooking process which is used in making coatings, corrosion protection materials, and electrode. and it has been verified that Coal tar pitch extract (CTPE) constitutes polycyclic aromatic hydrocarbons (PAHs) (87.91%) and monocyclic aromatic hydrocarbons, heterocyclic compounds and alkenes (the remaining total is 12.09%) using gas chromatography/mass spectrometry (GC/MS). In this study, we determine the lncRNA expression profile in CTPE group and control group. The key lncRNAs were screen out by using microarray analysis in defferent group. The experiment is divided into two groups: 22RV1 cells as control group, 22RV1 cells induced with Robustanoids A. then perform lncRNAs chips by Arraystar Human lncRNAs chip (Arraystar).
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Project description:Polycyclic aromatic hydrocarbons (PAHs) are a class of hundreds of structurally similar chemicals ubiquitously present in our environment. They are created during the incomplete combustion of organic materials, such as oil, wood, tobacco, and charbroiled meat. As such, human exposure to mixtures of PAHs can occur through consumption of PAH-containing foods and water, inhalation of polluted air, or dermal contact. Several PAHs have been classified as carcinogenic to humans or probably carcinogenic to humans by the International Agency for Research on Cancer. The mice in this study were exposed to a mixture of 4 PAHs, benzo(a)pyrene, benz(a)anthracene, benzo(b)fluoranthene, and chrysene. In the present study, we sought to determine the dose-dependent changes in gene expression upon oral exposure to this PAH mixture in the lung tissue. Adult male MutaTMMouse were exposed to three doses of the mixture of 4 PAHs or vehicle control (olive oil) for 28 days and sacrificed three days after the final exposure.
2017-01-01 | GSE87688 | GEO
Project description:Polycyclic aromatic hydrocarbons (PAHs) are a class of hundreds of structurally similar chemicals ubiquitously present in our environment. They are created during the incomplete combustion of organic materials, such as oil, wood, tobacco, and charbroiled meat. As such, human exposure to mixtures of PAHs can occur through consumption of PAH-containing foods and water, inhalation of polluted air, or dermal contact. Several PAHs have been classified as carcinogenic to humans or probably carcinogenic to humans by the International Agency for Research on Cancer. The mice in this study were exposed to a mixture of 8 PAHs, benzo(a)pyrene, benz(a)anthracene, benzo(b)fluoranthene, benzo(ghi)perylene, benzo(k)fluoranthene, chrysene, dibenz(ah)anthracene, and indeno(123,cd)pyrene. In the present study, we sought to determine the dose-dependent changes in gene expression upon oral exposure to this PAH mixture in the lung tissue. Adult male MutaTMMouse were exposed to three doses of the mixture of 8 PAHs or vehicle control (olive oil) for 28 days and sacrificed three days after the final exposure.
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