Accession Number:

ADA613630

Title:

Differentiated NSC-34 cells as an in vitro Cell Model for VX

Descriptive Note:

Journal article

Corporate Author:

ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD

Report Date:

2014-09-11

Pagination or Media Count:

8.0

Abstract:

The US military has placed major emphasis on developing therapeutics against nerve agents NA. Current efforts are hindered by the lack of effective in vitro cellular models to aid in the preliminary screening of potential candidate drugsantidotes. The development of an in vitro cellular model to aid in discovering new NA therapeutics would be highly beneficial. In this regard, we have examined the response of a differentiated hybrid neuronal cell line, NSC-34, to the NA VX. VX-induced apoptosis of differentiated NSC-34 cells was measured by monitoring the changes in caspase-3 and caspase-9 activity post-exposure. Differentiated NSC-34 cells showed an increase in caspase-3 activity in a manner dependent on both time 17 23 h postexposure and dose 10 100 nM. The maximal increase in caspase-3 activity was found to be at 20-h post-exposure. Caspase-9 activity was also measured in response to VX and was found to be elevated at all concentrations 10 100 nM tested. VX-induced cell death was also observed by utilizing annexin Vpropidium iodide flow cytometry. Finally, VX-induced caspase-3 or -9 activities were reduced with the addition of pralidoxime 2-PAM, one of the current therapeutics used against NA toxicity, and dizocilpine MK-801. Overall the data presented here show that differentiated NSC-34 cells are sensitive to VX-induced cell death and could be a viable in vitro cell model for screening NA candidate therapeutics.

Subject Categories:

  • Biology
  • Pharmacology
  • Chemical, Biological and Radiological Warfare

Distribution Statement:

APPROVED FOR PUBLIC RELEASE