title: Changing mutant frequencies in cell populations subjected to long-term fractionated doses of radiation may reflect selection for radioresistance.
abstract: Five populations of Chinese hamster ovary cells were exposed to daily doses of 40 mGy of gamma-radiation and sampled weekly for thioguanine-resistant mutant frequency. Over a period of 2-3 months, mutants appeared at frequencies above background in four of the populations, but not after the same cumulative doses. If followed long enough, mutant frequency, after increasing rapidly, peaked and then dropped again to the background level. Control populations did not behave in this way. Analysis of cellular resistance to radiation showed that the populations as a whole, after a cumulative dose of 2-3 Gy, exhibited a 30-105% greater resistance to an acute dose of 2 Gy, compared to untreated cells. However, analysis of subclones of these populations revealed great heterogeneity in the radioresistance levels, whereas subclones of unirradiated cell lines were uniform in this respect. We propose that this radiation regimen, which crudely approximates dose schedules received by occupationally exposed individuals, results in selective enrichment for radioresistant cells. The occasional mutant arising in a relatively resistant member of the population would therefore occupy a progressively larger niche, and further changes in population dynamics could explain the subsequent observed decreases.
mesh_terms: D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D009154:Mutation; D011836:Radiation Tolerance
chemical_list: D007041:Hypoxanthine Phosphoribosyltransferase