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NCER Grantee Research Project Results

Microsatellite Mutation Rates in Laboratory Deer Mice (Peromyscus maniculatus) Exposed to TNX

EPA Grant Number: FP916425
Title: Microsatellite Mutation Rates in Laboratory Deer Mice (Peromyscus maniculatus) Exposed to TNX
Investigators: Smith, Jordan N.
Institution: Texas Tech University
EPA Project Officer: Manty, Dale
Project Period: January 1, 2004 through December 31, 2006
Project Amount: $102,629
RFA: STAR Graduate Fellowships (2004)
Research Category: Fellowship - Toxicology , Academic Fellowships , Health Effects

Description:

Objective:

The U.S. Environmental Protection Agency has classified Royal Demolition Explosive (RDX) as a possible human carcinogen. The carcinogenic mechanism of RDX is unknown and could be caused by nitroso compounds (MNX, DNX, and TNX) formed via anaerobic transformation of RDX. This is an important environmental issue because RDX has been used as an explosive for both military purposes and civilian applications worldwide. In addition, these nitroso metabolites were discovered in groundwater beneath the Iowa Army Ammunition Plant. There exists a need to further understand the toxicity of these nitroso metabolites. To characterize the possible risks posed by these compounds, this project uses molecular genetic techniques as a means of detecting potential genetic effects. The main objective of this project is to answer the central research question: Does the exposure to the RDX metabolite TNX (hexahydro-1,3,5-trinitroso-1,3,5-triazine) alter the basal levels of microsatellite mutation rates in deer mice (Peromyscus maniculatus)?

Approach:

To answer this question, breeding pairs of laboratory deer mice will be exposed to TNX ad libitum via drinking water. TNX will be administered at four doses: 100 μg/L, 10 μg/L, 1 μg/L, and control (0 μg/L). Paired mice will be bred to produce offspring, which will be weaned on postnatal day 21. Offspring will receive exposure from conception until sacrifice at postnatal day 45. Effects of exposure to TNX will be investigated with the following endpoints: reproductive success, offspring survival, offspring weight gain, organ weights, and microsatellite mutation rate. To assess the microsatellite mutation rate, DNA will be obtained from frozen tissue of sacrificed mice. Fourteen mircosatellite loci will be amplified with polymerase chain reaction and analyzed for allelic differences using the parent/offspring approach of Mendelian inheritance. The number of mutations will be determined, and these results will be compared among the control and three experimental groups. Results could provide insight on potential teratogenic, reproductive, and mutagenic effects of these nitroso metabolites. These results also could play an important role in future policy decisions for remediation of contaminated sites.

Supplemental Keywords:

fellowship, Royal Demolition Explosive, RDX, carcinogen, nitroso compounds, MNX, TNX, DNX, toxicity, metabolite, mutation rates, microsatellite mutation rate, reproductive success, offspring survival, teratogenic effects, mutagenic effects, reproductive effects, deer mice, Peromyscus maniculatus,, Health, Scientific Discipline, ENVIRONMENTAL MANAGEMENT, Toxicology, Health Risk Assessment, Risk Assessments, Risk Assessment, mutagenic properties, nitroso compounds, carcinogenesis, bioavailability, animal model, exposure assessment, human health risk, maternal exposure, biochemical research

Relevant Websites:

2004 STAR Graduate Fellowship Conference Poster (PDF, 3pp., 230KB, about PDF)

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.

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