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| Status |
Public on Dec 31, 2016 |
| Title |
Using transcriptomics to evaluate thresholds in genotoxicity dose-response |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Several genotoxic chemicals have been reported to produce threshold-shaped dose-response curves for mutation and genotoxicity assays, both in vivo and in vitro. These data challenge the current default practice for risk assessment of genotoxic chemicals, which assumes a linear dose-response below the lowest tested dose. Due to the inherent challenges in data collection and analysis, statistical methods cannot determine whether a biological threshold exists with sufficient confidence to overturn this assumption of linearity. Indeed, to truly define the shape of the dose-response curves, we must look to the underlying biology and develop targeted experiments to identify and measure the key processes governing cellular response at low doses. This chapter describes a series of studies aimed at defining the transcriptional responses to DNA damage in an effort to identify the key processes regulating low-dose DNA damage response.
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| Overall design |
HT1080 cells were treated with multiple prototype compounds at a single chemical dose that led to a similar activation of p53-DNA damage pathway (1.5 fold increase in total p53)
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| Contributor(s) |
McMullen PD, Pendse SN, Adeleye Y, Charmichael PL, Andersen ME, Clewell RA |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Nov 05, 2015 |
| Last update date |
Apr 20, 2018 |
| Contact name |
Rebecca A Clewell |
| Organization name |
The Hamner Institutes for Health Sciences
|
| Department |
Institute for Chemical Safety Sciences
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| Street address |
6 Davis Drive
|
| City |
Research Triangle Park |
| State/province |
NC |
| ZIP/Postal code |
27709 |
| Country |
USA |
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| Platforms (1) |
| GPL13158 |
[HT_HG-U133_Plus_PM] Affymetrix HT HG-U133+ PM Array Plate |
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| Samples (101)
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| Relations |
| BioProject |
PRJNA301346 |
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