Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Cardiac and pulmonary responses to diesel engine particulate in Apo E(-/-) mice II

ABSTRACT: Mice deficient in Apolipoprotein E (Apoe E(-/-)) vs wild type mice were exposed to diesel engine particulate by single dose intratracheal instillation. The transcript-level response of the hearts after 24h and of the lungs after 24 h were subsequently analyzed by the 2-color microarray method. Keywords: stress response, disease state analysis Three mice of the Apo E (-/-) strain were exposed to diesel engine particulate from the National Institute of Standards and Technology via intratracheal instillation. Controls consisted of 3 littermates exposed to saline vehicle. Similarly, three wild type mice were similarly exposed to diesel particulate and three to vehicle control. 24 hours after exposure, mice were humanely sacrificed by carbon dioxide asphyxiation and the hearts and lungs were collected and frozen for analysis of total RNA. In each biological replicate, 2 color microarrays were utilized to compare pooled RNA representing all three animals of each strain, and in each condition and in each tissue; each biological replicate was performed with a dye reversal. Biological replicates of the wild type mice responses to diesel engine particulate were performed three times for heart and lung.

ORGANISM(S): Mus musculus

SUBMITTER: Darrow April

PROVIDER: E-GEOD-17331 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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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Cardiac and pulmonary responses to diesel engine particulate in Apo E(-/-) mice II

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