In vitro studies of the genotoxicity of ionizing radiation in human G 0 T lymphocytes

Patrick O'Neill, Janice Nicklas, Betsy Hirsch, Rick Jostes, Timothy Hunter, Linda Sullivan, Richard Albertini

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)207-220
Number of pages14
JournalEnvironmental and Molecular Mutagenesis
Volume46
Issue number4
DOIs
StatePublished - Dec 2005

Keywords

  • HPRT mutation
  • Human mutation
  • Ionizing radiation
  • T lymphocyte
  • Translocation

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