Hair Follicle Bulb as a Biodosimeter for Low-Level VX Vapor Exposure: Initial Studies Validating the Presence of Potential Protein Biomarkers of Exposure in the Sprague-Dawley Rat Whisker Follicle

摘要

Over the past fifty years, numerous studies have been performed to determine the health effects of exposure to organophosphorus (OP) nerve agents. The traditional approaches to determine OP exposure are invasive (e.g. require blood samples) laboratory-based assays that are not ideal for rapid, reliable testing in the event of a mass exposure scenario. However, advances in biomarker discovery make it possible to develop a less invasive, more expedient assay. The active hair follicle bulb expresses a large number of proteins, is easily accessible, and is an excellent candidate from which to assess biomarkers. In this report, we describe a novel immunohistochemistry (IHC) method developed for this initial hair follicle investigation, as well as the initial work completed to determine the presence of fifteen potential protein OP agent exposure biomarkers in the rat whisker follicle bulb. Each potential biomarker protein was chosen because of its change in expression in non-hair follicle tissue following exposure to pesticides and/or OP nerve agents. Using Western blotting, the expression of these proteins was verified in the rat whisker follicle bulb. Following verification in the digested hair follicle intact whole-hair IHC was performed to determine protein expression levels in the intact whisker follicle bulb.