Acute RDX exposure and gene expression in the rat brain

Bannon, DI; Dillman, JF; Perkins, EJ; Bao, W; Wolfinger, RD; Chu, T; Phillips, CS

HERO ID

627912

Reference Type

Book/Book Chapter

Subtype

Abstract

Year

2006

Language

English

HERO ID 627912
Material Type Abstract
Year 2006
Title Acute RDX exposure and gene expression in the rat brain
Authors Bannon, DI; Dillman, JF; Perkins, EJ; Bao, W; Wolfinger, RD; Chu, T; Phillips, CS
Publisher Text Oxford University Press
City Oxford, United Kingdom
Volume 90
Page Numbers 392-393
Abstract Hexahydro-1,3,5-trinitro-1,3,5-triazine is a synthetic, high-impact, relatively stable compound commonly known as Rapid Detonation Explosive (RDX) and has been used in munitions and formulations since World War II. The primary symptom of acute oral exposure to high doses in humans is transient and reversible seizure, accompanied by nausea, muscle spasms, and disorientation, which are also reported in experimental animals. The occurrence of these preventable effects in humans is often reported in occupational settings that lack standard industrial hygiene practices, resulting in high airborne exposures. Though several studies have correlated measurements of RDX in the brains and plasma of dosed animals with frank seizures, little work has been carried out on the effects of RDX at the molecular level. In this study, we examined the impact of a single orally administered RDX dose on the brain, using a combination of analytical chemistry and genechip microarrays. At nominal doses of 3 and 18 mg/kg in male adult rats, a time course of RDX tissue levels showed peak brain concentrations at 3.5 hours, returning to baseline at 24 and 48 hours, respectively. RNA from dosed and control animals was hybridized to Affymetrix Rat 230 2.0 arrays. Analysis was performed in JMP Genomics with the differentially expressed gene cut-off at p > 0.001. We found sets of genes that were early and late responders to RDX treatment. In addition, pathway analysis indicated effects on the nervious system, cell-to-cell signalling, and cell development, among others. These results represent a preliminary basis for understanding the molecular mechanisms underlying RDX toxicity, and further work is underway.
Url http://www.toxicology.org/pubs/docs/Tox/2006Tox.pdf
Is Certified Translation No
Dupe Override 627912
Conference Name Society of Toxicology Annual Meeting
Is Public Yes
Language Text English
Is Qa No