Diverse Delayed Effects in Human Lymphoblastoid Cells Surviving Exposure to High-LET56Fe Particles or Low-LET137Cs Gamma Radiation

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Abstract
Evans, H. H., Horng, M. F., Ricanati, M., Diaz-Insua, M., Jordan, R. and Schwartz, J. L. Diverse Delayed Effects in Human Lymphoblastoid Cells Surviving Exposure to High-LET 56Fe Particles or Low-LET 137Cs Gamma Radiation. Radiat. Res. 156, 259–271 (2001). To obtain information on the origin of radiation-induced genomic instability, we characterized a total of 166 clones that survived exposure to 56Fe particles or 137Cs γ radiation, isolated approximately 36 generations after exposure, along with their respective control clones. Cytogenetic aberrations, growth alterations, responses to a second irradiation, and mutant frequencies at the Na+/K+ ATPase and thymidine kinase loci were determined. A greater percentage of clones that survived exposure to 56Fe particles exhibited instability (defined as clones showing one or more outlying characteristics) than in the case of those that survived γ irradiation. The phenotypes of the unstable clones that survived exposure to 56Fe particles were also qualitatively different from those of the clones that survived γ irradiation. A greater percentage (20%) of the unstable clones that survived γ irradiation than those that survived exposure to 56Fe particles (4%) showed an altered response to the second irradiation, while an increase in the percentage of clones that had an outlying frequency of ouabain-resistant and thymidine kinase mutants was more evident in the clones exposed to 56Fe particles than in those exposed to γ rays. Growth alterations and increases in dicentric chromosomes were found only in clones with more than one alteration. These results underscore the complex nature of genomic instability and the likelihood that radiation-induced genomic instability arises from different original events.