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, G₀ phase T lymphocytes from human peripheral blood samples were utilized for in vitro studies of the genotoxic effects of ¹³⁷Cs low-LET irradiation and ²²²Rn 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 + 7.51x² for ¹³⁷Cs (R² = 0.95) and MF = 4.81 + 0.67x for ²²²Rn (R² = 0.51). Post ¹³⁷Cs 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 ¹³⁷Cs 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 ²²²Rn 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.