Rodent bedding, diet, and drinking water may contain compounds that affect the same endpoints that are the target of NTP's testing program, such as reproduction and development. For example, endotoxins (a byproduct of mold) can mask responses to exposure to asthma-causing agents. Likewise, phytoestrogens in the rodent diet can mask responses to exposure to estrogenic compounds. We are working with the NIEHS Quality Assurance Laboratory to quantify these effects and develop guidelines for limits on contaminants in bedding, diet and drinking water of rodent studies. We contributed to a mouse study of the role of genetic diversity in responding to ionizing radiation. Known as the """"""""Diversity Outcross"""""""", eight strains of mice were interbred to generate genetic heterogeneity approximating the degree of heterogeneity seen in humans. Mice were exposed to ionizing radiation (or control) then assessed for formation of micronucleated cells in blood and bone marrow;micronucleated cells are indicators of chromosome damage. Preliminary data show that there is a wide range of responses to radiation among the strains. We have identified two areas, located within chromosome 2 and chromosome 10, that may explain differences in susceptibility. The NTP often collects a large number of tissue samples in a single study and it may not be feasible to immediately assay all samples;samples may need to be stored for later analysis. To ensure that the data collected from stored tissue samples remains of high quality, we collaborated on the design and statistical analysis of several studies to examine the stability of hematology, clinical chemistry and genetic toxicity measurements made on tissues having differing storage conditions, i.e., length of time stored and storage temperature. So far, we have established that comet assay results remain stable when tissue is frozen for up to 8 weeks.
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