Research Project
3165058
The primary objectives of the proposed research are: a) to examine the nature of (and relations between) ultraviolet and ionizing radiation induced lethal lesions and lesions leading to chromosomal aberrations in vertebrate cells, b) to explore intracellular processes triggered by radiation which lead to aberrations and cell death, c) to explore mechanisms by which cells repair or otherwise recover from such lesions. Synchronous cultures of interphase nonmammalian vertebrate cells which possess efficient photorepair, mammalian cells lacking efficient photorepair, and mammalian-nonmammalian hybrid cells are to be treated with combinations of gamma radiation, ultraviolet light, photoreactivating light, metabolic inhibitors and hyperthermia. At appropriate intervals following these treatments, cells are assayed for types of aberrations, aberration frequencies, reproductive death, and related repair. This approach is yielding dose-survival and dose-aberrational kinetics which appear essential for a more complete description of relations between radiation-induced aberration production and cell killing, and the roles of intracellular repair mechanisms in vertebrate cell radiosensitivity. Some of these kinetics could have implications for improvements in the therapeutic uses of radiation. The studies of radiation-induced aberration production and related repair, as a function of position in the cell cycle, could assist in describing changes in interphase chromosome structure as cells progress through the cell cycle. Any elucidation of the structure and organization of interphase chromosomes would likely assist in the description of genetic mechanisms of interest in many areas of biomedical science.
