Aneuploidy is the most common constitutive chromosomal abnormality in humans. Most aneuploidy in humans is considered to be of germ cell origin, arising from errors in maternal or paternal meiotic chromosomal segregation. A method for detecting aneuploidy in human sperm using fluorescence in situ hybridization (FISH) has recently been developed. The parallel animal model tests being developed under this project will be used to evaluate the aneugenic potential of environmental chemicals tested in NTP bioassays and answer critical questions regarding the mechanisms of aneuploidy induction which cannot be addressed in human studies. Methodology for a three chromosome (X, Y, and 8) sperm-FISH assay has been developed at Lawrence Livermore National Laboratory (LLNL) under an NIEHS-DOE Interagency agreement 10203. This method requires evaluation through positive control experiments. For this purpose, male mice were treated at NIEHS (TB 92-01) with Novantrone, Oncovin or Vinblastine. Hematological evaluations were conducted at NIEHS. The pathology of testicular sections from these mice is currently being evaluated at NIEHS and sperm-FISH is being evaluated at LLNL. The results of these evaluations will be used to select dose levels for a treatment regimen combining these chemicals to model a similar study of aneuploidy in human sperm obtained from Hodgkin's patients. Plasmid DNA with inserts for the mouse X, Y, and 8 chromosomes have been cloned and biotin labeled at NIEHS in preparation for use in sperm-FISH experiments with NTP chemicals.
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