In vitro studies of the genotoxicity of ionizing radiation in human G(0) T lymphocytes.
In an effort to mimic human in vivo exposures to ionizing irradiation, G(0) phase T lymphocytes from human peripheral blood samples were utilized for in vitro studies of the genotoxic effects of (137)Cs low-LET irradiation and (222)Rn high-LET irradiation. Both types of radiation induced mutations in the HPRT gene in a dose-dependent manner, with a mutant frequency (MF) = 4.28 + 1.34x + 7.51x(2) for (137)Cs (R(2) = 0.95) and MF = 4.81 + 0.67x for (222)Rn (R(2) = 0.51). Post (137)Cs irradiation incubation in the presence of cytosine arabinoside, a reversible inhibitor of DNA repair, caused an increase in the MF over irradiation alone, consistent with a misrepair mechanism being involved in the mutagenicity of low-LET irradiation. The spectrum of (137)Cs irradiation-induced mutation displayed an increase in macro-deletions (in particular total gene deletions) and rearrangement events, some of which were further defined by either chromosome painting or direct DNA sequencing. The spectrum of (222)Rn irradiation-induced mutation was characterized by an increase in small alterations, especially multiple single base deletions/substitutions and micro-deletions. These studies define the specific response of human peripheral blood T cells to ionizing irradiation in vitro and form a basis for evaluating the genotoxic effects of human in vivo exposure.
O'Neill
Patrick
P
University of Vermont, Genetics Laboratory, Burlington, VT 05405, USA. patrick.oneill@uvm.edu
Nicklas
Janice
J
Hirsch
Betsy
B
Jostes
Rick
R
Hunter
Timothy
T
Sullivan
Linda
L
Albertini
Richard
R
D002455:Cell Division; D049109:Cell Proliferation; D002478:Cells, Cultured; D002588:Cesium Radioisotopes; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics* / Q000528:radiation effects*; D018499:Linear Energy Transfer; D009152:Mutagenicity Tests; D009154:Mutation; D011839:Radiation, Ionizing; D011886:Radon; D016192:Resting Phase, Cell Cycle / Q000528:radiation effects*; D013601:T-Lymphocytes / Q000166:cytology / Q000528:radiation effects*
D002588:Cesium Radioisotopes; D007041:Hypoxanthine Phosphoribosyltransferase; D011886:Radon