Abstract
We performed a pilot study to characterize the molecular, cellular, and whole-organism response to nonlethal chemical agent exposure in the central nervous system. Multiple methodologies were applied to measure in vitro enzyme inhibition, neuronal cell pathway signaling, and in vivo zebrafish neural development in response to challenge with two different classes of chemical compounds. While all compounds tested exhibited expected enzyme inhibitory activity against acetylcholinesterase (AChE), a well-characterized target of chemical agents, distinct differences between chemical exposures were detected in cellular toxicity and pathway target responses and were tested in a zebrafish model. Some of these differences have not been detected using conventional chemical toxicity screening methods. Taken together, the data demonstrate the potential value of an integrated, multimethodological approach for improved target and pathway identification for subsequent diagnostic and therapeutic biomarker development.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 441-451 |
| Number of pages | 11 |
| Journal | Johns Hopkins APL Technical Digest (Applied Physics Laboratory) |
| Volume | 32 |
| Issue number | 1 |
| State | Published - Jun 2013 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Engineering(all)
- Physics and Astronomy(all)
Cite this
Integrated approach for identifying the molecular, cellular, and host responses to chemical insults. / Fischer, Audrey E.; English, Emily P.; Patrone, Julia B.; Santos, Kathlyn; Proescher, Jody B G; Quizon, Rachel S.; Van Houten, Kelly A.; Pilato, Robert S.; Van Gieson, Eric J.; Carruth, Lucy M.
In: Johns Hopkins APL Technical Digest (Applied Physics Laboratory), Vol. 32, No. 1, 06.2013, p. 441-451.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Integrated approach for identifying the molecular, cellular, and host responses to chemical insults
AU - Fischer, Audrey E.
AU - English, Emily P.
AU - Patrone, Julia B.
AU - Santos, Kathlyn
AU - Proescher, Jody B G
AU - Quizon, Rachel S.
AU - Van Houten, Kelly A.
AU - Pilato, Robert S.
AU - Van Gieson, Eric J.
AU - Carruth, Lucy M.
PY - 2013/6
Y1 - 2013/6
N2 - We performed a pilot study to characterize the molecular, cellular, and whole-organism response to nonlethal chemical agent exposure in the central nervous system. Multiple methodologies were applied to measure in vitro enzyme inhibition, neuronal cell pathway signaling, and in vivo zebrafish neural development in response to challenge with two different classes of chemical compounds. While all compounds tested exhibited expected enzyme inhibitory activity against acetylcholinesterase (AChE), a well-characterized target of chemical agents, distinct differences between chemical exposures were detected in cellular toxicity and pathway target responses and were tested in a zebrafish model. Some of these differences have not been detected using conventional chemical toxicity screening methods. Taken together, the data demonstrate the potential value of an integrated, multimethodological approach for improved target and pathway identification for subsequent diagnostic and therapeutic biomarker development.
AB - We performed a pilot study to characterize the molecular, cellular, and whole-organism response to nonlethal chemical agent exposure in the central nervous system. Multiple methodologies were applied to measure in vitro enzyme inhibition, neuronal cell pathway signaling, and in vivo zebrafish neural development in response to challenge with two different classes of chemical compounds. While all compounds tested exhibited expected enzyme inhibitory activity against acetylcholinesterase (AChE), a well-characterized target of chemical agents, distinct differences between chemical exposures were detected in cellular toxicity and pathway target responses and were tested in a zebrafish model. Some of these differences have not been detected using conventional chemical toxicity screening methods. Taken together, the data demonstrate the potential value of an integrated, multimethodological approach for improved target and pathway identification for subsequent diagnostic and therapeutic biomarker development.
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UR - http://www.scopus.com/inward/citedby.url?scp=84881323187&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:84881323187
VL - 32
SP - 441
EP - 451
JO - Johns Hopkins APL Technical Digest (Applied Physics Laboratory)
JF - Johns Hopkins APL Technical Digest (Applied Physics Laboratory)
SN - 0270-5214
IS - 1
ER -