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| Status |
Public on Aug 01, 2012 |
| Title |
Polycyclic aromatic hydrocarbons as skin carcinogens: Comparison of benzo[a]pyrene, dibenzo[def,p]chrysene and three environmental mixtures in the FVB/N mouse |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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).
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| Overall design |
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 μl), BaP 400 nmol (100 μg), DBC 4 nmol (1.2 μg), or to mixtures of environmental PAH mixtures containing diesel particulate extract, coal tar extract, or cigarette smoke condensate.
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| Contributor(s) |
Tilton SC, Williams DE |
| Citation(s) |
22935520, 25908611 |
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| Submission date |
Jul 18, 2012 |
| Last update date |
Feb 02, 2018 |
| Contact name |
Susan C. Tilton |
| E-mail(s) |
Susan.Tilton@oregonstate.edu
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| Organization name |
Oregon State University
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| Department |
AG Envr & Molec Toxicology
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| Street address |
1007 ALS Bldg
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| City |
Corvallis |
| State/province |
OR |
| ZIP/Postal code |
97331 |
| Country |
USA |
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| Platforms (1) |
| GPL10787 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version) |
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| Samples (25)
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| Relations |
| BioProject |
PRJNA171688 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE39455_RAW.tar |
304.7 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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