TA2 Molecular Indicators for Ecological Exposure
255 Portland Ballroom
8:00 AM - 12:00 PM, Tuesday
() Potential molecular markers for monitoring exposure to ordnance related chemicals.
Perkins , E1, Inouye , L1, Guan, X2, 1 US Army Engineer Research and Development Center, Vicksburg, MS, USA2 ASI, Vicksburg, MS, USA
ABSTRACT- The ongoing and historical use of explosives by the military has resulted in release of RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) and the anaerobic degradation product MNX (hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine. Oral dosing studies indicate that high doses of RDX and MNX can cause neuromuscular effects in rats (Rattus norvegicus) and Northern Bobwhite (Colinus virginianus). We have begun an effort to understand potential sublethal effects and develop molecular markers of exposure to MNX in a model rodent and laboratory species. Oligonucleotide microarrays were used to examine potential markers of exposure in Sprague Dawley rats. Rats were orally exposed to different levels of MNX. Short term exposure, 12 and 24 hours, indicated toxicant metabolism was occurring in addition to cellular and DNA damage and repair in the liver. Gene expression was also examined in liver and brain tissues of animals 14 days after exposure. Microarray analyses suggest that the central nervous system was still greatly altered 2 weeks after exposure. Livers of these same animals had fewer than 20 genes with altered expression. In conjunction with observed neurological effects such as seizures and lack of any observable effects on other organs, this data identifies pathways and molecular targets for understanding and monitoring potential sublethal effects of ordnance degradation products.
Key words: explosives, toxicogenomics, microarray