Through collaborative research involving Texas Tech University (TTU) and The Idaho National Environmental and Engineering Laboratory (INEEL), the genotoxicity of High explosives (HE) and HE transformation products is being evaluated. Our current research focuses on Royal Demolition Explosive (RDX: hexahydro-1,3,5-trinitro-1,3,5-triazine). In the current line of research we are evaluating the toxicity of nitroso-transformation products. Specifically we are testing the hypothesis: Nitroso transformation products of (RDX) will be mutagens in deer mice (peromyscus maniculatus). The specific sub-hypothesis to be tested in this proposal is: Hexahydro-1,3,5-trinitroso-1,3,5,-triazine (TNX) will cause microsatellite mutations in deer mice (Peromyscus maniculatus). We have determined a dose dependent increase in microsatellite lenghts in mice administered 0,1,10 , and 100 mu g/L TNX. These concentrations are below those found in groundwaters near military installations and explosives production facilities. Thus, we propose a study to sequence peromyscus microsatellite alleles whose lengths have been altered by TNX exposure and an equal number of alleles whose lengths have not been altered. This design is employed to determine if the allelic alterations are simple slippage or if aberrant bases have been inserted into the microsatellites. Sequencing alleles with altered and unaltered numbers of bases will allow us to determine if base replacements have occurred and if these replacements occur with greater frequency than do changes in sequence length. This project will begin laying the groundwork to evaluate the genotoxicity of N-nitrosamine metabolites of RDX, the most widely used military and industrial explosive in the US. These compounds are found in groundwaters beneath several hazardous waste sites and firing ranges. Human exposure to these chemicals is likely since explosives contaminated groundwaters are the sole source of drinking water in some areas.
