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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 18, 2015 |
| Title |
Transcriptional Response of Male MutaTMMouse Spleen to Dibenzo[def,p]chrysene Exposure |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Dibenzo[def,p]chrysene (DBC) is the most carcinogenic polycyclic aromatic hydrocarbon (PAH) examined to date. We investigated the immunotoxicity of DBC, manifested as spleen atrophy following acute exposure of adult Muta™Mouse males by oral gavage. Mice were exposed to 0, 2.0, 6.2, or 20.0 mg DBC /kg-bw per day, for three days.
Genotoxic endpoints (DBC-DNA adducts and lacZ mutant frequency in spleen and bone marrow, and red blood cell micronucleus frequency) and global gene expression changes were measured. All of the genotoxicity measures increased in a dose-dependent manner in both tissues.
Gene expression analysis showed that DBC activates p53 signalling pathways related to cellular growth and proliferation, which was evident even at the low dose. Strikingly, the expression profiles of DBC exposed mouse spleens were highly inversely correlated with the expression profiles of the only published toxicogenomics dataset of enlarged mouse spleen.
This analysis suggested a central role for Bnip3l, a pro-apoptotic protein involved in negative regulation of erythroid maturation. RT-PCR confirmed expression changes in several genes related to apoptosis, iron metabolism, and aryl hydrocarbon receptor signalling that are regulated in the opposite direction during spleen atrophy versus benzo[a]pyrene-mediated splenomegaly.
In addition, benchmark dose modeling of toxicogenomics data yielded toxicity estimates that are very close to traditional toxicity endpoints. This work illustrates the power of toxicogenomics to reveal rich mechanistic information of immunotoxic compounds and its ability to provide information that is quantitatively similar to that derived from standard toxicity methods in health risk assessment.
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| Overall design |
Four to five (N=4-5) biological replicates were analyzed per sample for each of the three doses, plus a control, four or 24 h after the last treatment.
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| Contributor(s) |
Chepelev NL, Long AS, Williams A, Kuo B, Gagné R, Kennedy DA, Phillips DH, Arlt VM, White PA, Yauk CL |
| Citation(s) |
26496743 |
| Submission date |
Aug 24, 2015 |
| Last update date |
Feb 02, 2018 |
| Contact name |
Nikolai L Chepelev |
| E-mail(s) |
nikolai.chepelev@gmail.com
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| Phone |
6138985388
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| Organization name |
Health Canada
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| Department |
Environmental Health Science and Research Bureau
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| Lab |
Genomics Laboratory
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| Street address |
50 Colombine Driveway
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| City |
Ottawa |
| State/province |
Ontario |
| ZIP/Postal code |
K1A0K9 |
| Country |
Canada |
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| Platforms (1) |
| GPL10787 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version) |
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| Samples (37)
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| Relations |
| BioProject |
PRJNA293761 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE72334_RAW.tar |
222.8 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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