CYTOGENETICS--ALPHA PARTICLE INDUCED CHROMOSOMAL CHANGES

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Attribution of the principal ionizing radiation hazard to humans as being due to radon is based on the pervasive nature of the gas and perceived biological efficacy of the responsible high LET alpha particles. While it has long been recognized that radiation of high LET may be more biologically damaging, there is in many instances a decline past an optimally effective LET. Ascertainment of the effectiveness of alpha particles over the range of LET's relevant to radon will allow for greater precision in human risk estimates. This is particularly pertinent for environmental levels of radon where the principal cellular insult is from one and only one radon progeny a-particle. The issues to be addressed relate to the primary overall goals of the program project, namely the provision of information on the effects of single a-particles; to assessments of RBE: LET relations to contribute to quality factor estimates; and to seek a characteristic "fingerprint" for a=-particle exposure. Chromosomal changes have been shown to be associated with cell death, mutation and cancer and their quantitative evaluation is the linch pin of this project and provides links with the other projects of this program project. The effects of exactly one or more a-particles per cell nucleus delivered by microbeam will be compared with the effects of mean (Poisson distributed) numbers of a-particles at the same defined LET in normal human bronchial epithelial cells and fibroblasts. The former constitute the principal cell type at risk from radon progeny a-particle exposure. Chromosomal changes induced by defined high LET a-particles will be compared with X-ray induced changes. Changes will be quantitatively evaluated in normal human bronchial epithelial cells in different stages of the cell cycle, both for all changes and for chromosome specific change using FISH. Inter versus intrachromosomal exchange ratios will be compared for a-particles versus X-rays in a search for a dependent consequence of a- particle radiation. Information gained will be analyzed and incorporated into an integrated modeling of biological data and risk estimation (Project 1) with the intent of providing both a more credible assessment of risk and possible a means of accurately attributing alpha particle (radon) induced change.