The primary objectives of the research are: (a) elucidation of the nature of (and relations between) ultraviolet and ionizing radiation-induced lethal lesions and lesions leading to chromosomal aberrations in mammalian and other vertabrate cells, (b) enhancement of understanding of intracellular processes, triggered by these lesions which express the lesions as aberrations and cell death, (c) enhancement of understanding of intracellular mechanisms by which cells repair or otherwise recover from such lesions. A secondary objective is to carefully examine the results of those studies conducted in pursuance of objectives a, b, and c for clues and implications which could be of value in examining questions of changes in vertebrate chromosome structure and organization as cells progress through the cell cycle. 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, photo-reactivating light, and metabolic inhibitors. At appropriate intervals following these treatments, cells are assayed for types of chromosomes breaks, types of aberrations, frequencies of chromosome breaks, frequencies of aberrations, reproductive death, and related repair. This approach is yielding dose-survival, dose-chromosome breakage, 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 chromosome breakage, 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.
| Kulp, S Q; Griggs, H G (1989) Photoreactivation of lethal damage and damage leading to chromatid deletions induced in G1 phase hamster x Xenopus hybrid cells by UV. Photochem Photobiol 50:185-91 |
