ToxSci Advance Access originally published online on September 3, 2009
Toxicological Sciences 2009 112(1):1-3; doi:10.1093/toxsci/kfp193
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© The Author 2009. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Hypoxia Response: A Model Toxicity Pathway for High-Throughput Screening
Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711
1 For correspondence via Fax: (919) 541-3335. E-mail: simmons.steve@epa.gov.
Received August 5, 2009; accepted August 10, 2009
| The first 10% of the full text of this article appears below. |
The identification of toxicity pathways associated with known adverse health effects combined with engineered cellular assays that measure perturbations of these pathways is the keystone to the successful implementation of the recently formulated National Research Council (2007)
report, Toxicity Testing in the 21st Century: A Vision and a Strategy. While the toxicology community probes biological space to define the edges of what may be confidently considered "toxicity pathways," some well-characterized cellular signaling pathways will clearly fall within any reasonable definition of the term and represent first-tier candidates for immediate testing. Hypoxia response, like several of the toxicity pathway examples cited in the NRC report such as DNA damage response and Nrf2-mediated antioxidant response, is a key cellular stress response pathway that enables a cell to combat a variety of stressors. Although, there is a long-standing debate as to whether adaptive response
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