GENETIC TOXICITY IN BACTERIA AND RODENTS

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25 microbial mutagenicity assays have been completed and 22 in vivo micronucleus assays have been finalized during the fiscal year. At ILS, a comparative study of micronucleus (MN) enumeration in mice and rats by flow cytometry (FCM) and microscopy for 4 chemicals has been completed and the data published. Technology transfer and proficiency at ILS using a flow-based MN determination method has been demonstrated and based on the results of the comparative study mentioned above, the automated flow-based procedure has now replaced the more labor-intensive and less robust slide-based method. The NTP Genetic Toxicity data base has been updated to accept the new flow-derived data, and the data analysis methods have been updated and programmed into the data base, providing more appropriate methods of analyzing the larger number of cells scored with the automated flow cytometry system. Quantification of the fluorescence intensity for each MN as a potential marker for aneuploidy appears to be useful and is routinely done in those studies that show an elevated frequency of MN following exposure to a chemical. The Comet assay for measuring DNA damage levels is being used at ILS in these same in vivo studies; a variety of tissues are being analyzed for induced DNA damage in both the acute and the subchronic dosing studies. NTP is building a data base from which to determine if routinely combining Comet analysis with MN analysis in NTP study animals provides added benefit to assessing chemical toxicity. Sperm samples from mice exposed to a known inducer of chromosomal damage in somatic cells are being analyzed using the sperm FISH CT8 assay to determine if increased levels of chromosomal damage are detected in germ cells as a consequence of exposure to this compound. This exercise is being conducted to help better define the sensitivity of the CT8 assay in detecting germ cell mutagens. Keywords: Micronuclei; Ames test; salmonella; mutation; chromosomal damage