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| Status |
Public on Aug 07, 2013 |
| Title |
Long-term exposure to low-concentrations of Cr(VI) induce DNA damage and disrupt the transcriptional response to benzo[a]pyrene |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Living organisms are exposed on a daily basis to widespread mixtures of toxic compounds. Mixtures pose a major problem in the assessment of health effects because they often generate substance-specific effects that cannot be attributed to a single mechanism. Two compounds often found together in the environment are the heavy metal chromium and the polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P). We have examined how long-term exposure to a low concentration of Cr(VI) affects the transcriptional response to B[a]P, a second toxicant with an unrelated mechanism of action. Growth of mouse hepatoma cells for 20 passages in medium with 0.1 or 0.5 uM Cr(VI) increases DNA damage and apoptosis and decreases clonogenic ability. These cells also show transcriptome changes indicative of increased expression of DNA damage response and repair genes. In them, B[a]P activates cancer progression pathways, unlike cells never exposed to Cr(VI), where B[a]P activates mostly xenobiotic metabolism pathways. Cells grown in Cr(VI) for 20 passages and then cultured for an additional 5 passages in the absence of Cr(VI) recover from some but not all the chromium effects. They show B[a]P-dependent transcriptome changes strongly weighted towards xenobiotic metabolism, similar to those in B[a]P-treated cells that had no previous Cr(VI) exposure, but retain a high level of Cr(VI)-induced DNA damage and silence the expression of DNA damage and cancer progression genes. We conclude that the combined effect of these two toxicants appears to be neither synergistic nor cumulative, generating a toxic/adaptive condition that cannot be predicted from the effect of each toxicant alone.
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| Overall design |
Mouse Hepa-1 cells treated with Cr, Bap, Cr+Bap and untreated were profiled using RNAseq in duplicates.
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| Contributor(s) |
Ovesen JL, Fan Y, Chen J, Medvedovic M, Puga A |
| Citation(s) |
24374135, 33319643 |
| |
| Submission date |
Aug 06, 2013 |
| Last update date |
Feb 08, 2022 |
| Contact name |
Mario Medvedovic |
| Organization name |
University of Cincinnati
|
| Department |
Department of Environmental Health
|
| Lab |
Laboratory for Statistical Genomics and Systems Biology
|
| Street address |
3223 Eden Av. ML 56
|
| City |
Cincinnati |
| State/province |
OH |
| ZIP/Postal code |
45267-0056 |
| Country |
USA |
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| Platforms (1) |
| GPL15103 |
Illumina HiSeq 1000 (Mus musculus) |
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| Samples (20)
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| Relations |
| BioProject |
PRJNA214319 |
| SRA |
SRP028536 |
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