Integrated approach for identifying the molecular, cellular, and host responses to chemical insults

Audrey E. Fischer, Emily P. English, Julia B. Patrone, Kathlyn Santos, Jody B.G. Proescher, Rachel S. Quizon, Kelly A. Van Houten, Robert S. Pilato, Eric J. Van Gieson, Lucy M. Carruth

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)441-451
Number of pages11
JournalJohns Hopkins APL Technical Digest (Applied Physics Laboratory)
Volume32
Issue number1
StatePublished - Jun 1 2013

ASJC Scopus subject areas

  • Engineering(all)
  • Physics and Astronomy(all)

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    Fischer, A. E., English, E. P., Patrone, J. B., Santos, K., Proescher, J. B. G., Quizon, R. S., Van Houten, K. A., Pilato, R. S., Van Gieson, E. J., & Carruth, L. M. (2013). Integrated approach for identifying the molecular, cellular, and host responses to chemical insults. Johns Hopkins APL Technical Digest (Applied Physics Laboratory), 32(1), 441-451.