Together with the other projects of this Program Project on the effects of low doses of ionizing radiations the aim is to derive both an understanding of the means by which radiation produces biological effects and to use derived information to aid in the promulgation of rational standards for human protection. Chromosomal changes manifest in many areas of human concern and studies carried out supported by this Program Project has stressed the relationship between energy deposition events in cells and subsequent chromosomal changes recorded at mitosis. Having established such relationships for rodent cells the emphasis in this proposal will be on the characterization of chromosome specific changes in normal human cells. To this end normal human fibroblasts, keratinocytes and melanocytes of common genetic origin (to ensure that responses reflect cell type specificities) will be irradiated with defined sources of ionizing radiations (gamma rays and accelerated charged particles). Fluorescent chromosome specific DNA probes will enable changes in individual human chromosomes to be ascertained by fluorescent in situ hybridization (FISH). Additionally, all classes of gross chromosomal changes particularly translocations, can be recognized and quantified. Interaction frequencies between specific chromosomes will be determined to assess whether lesion interaction is random or non- random. Emphasis will be placed on those chromosomes that are the repositories of known oncogenes. Intranuclear chromosomal morphology will also be assessed with the intent of assessing dynamic likelihoods of chromosomal interactions. The relationship between initial lesions and ultimate chromosomal changes will be assessed for low energy (< 0.5 MeV) neutrons in normal human cells. Premature chromosome condensation (PCC) induction will take place immediately or at defined intervals post irradiation and fragment frequencies contrasted with aberration frequencies determined at the following mitosis. Quantitative light and fluorescence microscopic studies of individual chromosomes and cells, using defined cellular sources on one hand, in conjunction with defined radiation sources unique to this laboratory on the other hand will provide information of value to radiation biology and an understanding of the potential impact of ionizing radiations on human populations.
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