Neurotoxicogenomic investigations to assess mechanisms of action of the munitions constituents RDX and 2,6-DNT in Northern bobwhite (Colinus virginianus).
Toxicol Sci, 2009/7;110(1):168-80.
Gust KA[1], Pirooznia M, Quinn MJ Jr, Johnson MS, Escalon L, Indest KJ, Guan X, Clarke J, Deng Y, Gong P, Perkins EJ
Affiliations
PMID: 19417177DOI: 10.1093/toxsci/kfp091
Impact factor: 4.109
Abstract
Munitions constituents (MCs) including hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), 2,4,6-trinitrotoluene (TNT), and TNT derivatives are recognized to elicit aberrant neuromuscular responses in many species. The onset of seizures resulting in death was observed in the avian model Northern bobwhite after oral dosing with RDX beginning at 8 mg/kg/day in subacute (14 days) exposures, whereas affective doses of the TNT derivative, 2,6-dinitrotoluene (2,6-DNT), caused gastrointestinal impacts, lethargy, and emaciation in subacute and subchronic (60 days) exposures. To assess and contrast the potential neurotoxicogenomic effects of these MCs, a Northern bobwhite microarray was developed consisting of 4119 complementary DNA (cDNA) features enriched for differentially-expressed brain transcripts from exposures to RDX and 2,6-DNT. RDX affected hundreds of genes in brain tissue, whereas 2,6-DNT affected few (
MeSH terms
Animals; Chromatography, High Pressure Liquid; Colinus; Computational Biology; DDT; DNA, Complementary; Dinitrobenzenes; Dose-Response Relationship, Drug; Explosive Agents; Female; Gene Expression Profiling; In Situ Hybridization; Insecticides; Male; Neurotoxins; Oligonucleotide Array Sequence Analysis; RNA; Reverse Transcriptase Polymerase Chain Reaction; Toxicogenetics; Triazines
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