There is accumulating evidence for delayed genomic instability following radiation exposure. Specific aims are: (1) to investigate directly whether the origination event is located intra- or extra-nuclearly to study delayed chromosomal instability in a hamster -human hybrid cell line using fluorescence in situ hybridization to examine populations of metaphase cells several generations after expanding single-cell colonies that had survived five or ten alpha particles either to the nucleus or to the cytoplasm. Delayed chromosomal instability, manifested as multiple rearrangements of human chromosome 4 in a background of hamster chromosomes, will be observed. For both irradiated groups, correlations will be investigated between delayed chromosomal instability and delayed reproductive cell death, manifested as reduced plating efficiency in surviving clones: such correlations would suggest a role for chromosome rearrangements in cytotoxicity.