Defining the effects of radioprotective agents on mutant frequency and mutational spectra after exposure to {gamma}-radiation
- Univ. of Vermont, Burlington, VT (United States)
- Argonne National Laboratory, IL (United States)
The human T-lymphocyte cloning assay can be used to determine hprt mutant frequency induced by in vitro exposure to genotoxicants. Gamma radiation has been shown to produce increases in mutant frequency (Mf) and large deletions in the hprt gene in vivo and in vitro. The aminothiol radioprotector WR-1065 has been shown to reduce radiation-induced lethality and mutation in vitro. We are currently investigating in vitro effects of {gamma}-radiation exposure on Mf and mutational spectra after treatment with the aminothiol, WR-1065. G{sub o} lymphocytes, isolated from a blood sample were exposed to 3 Gy of {gamma}-radiation after a thirty minute exposure to 4mM WR-1065. Data on relative survival and mutant frequencies have been collected from two different blood samples. Relative survival decreased after 3 Gy gamma radiation (mean relative survival = 24%) whereas the mean relative survival for T-lymphocytes irradiated for 3 Gy after treatment with WR-1065 was {approximately}47%. Hprt mutant frequencies increased 9-12 fold over non-irradiated, non-treated controls when exposed to {gamma}-radiation. However, when WR-1065 was added thirty minutes prior to irradiation, mutant frequencies returned to control levels. WR-1065 treatment alone showed no cytoxicity and may possibly decrease Mf below control values. Molecular studies of hprt mutants isolated from these in vitro exposures are underway to determine what types of alterations occur in T-lymphocytes after exposure to ionizing radiation and how this spectrum changes following WR-1065 treatment. The spectrum of mutations seen in these treatment groups may provide evidence for what types of DNA damage are eliminated when radioprotectors are present, and may reveal the underlying mechanism(s) of radiation-induced metagenesis.
- OSTI ID:
- 88804
- Report Number(s):
- CONF-9405324--
- Journal Information:
- Environmental and Molecular Mutagenesis, Journal Name: Environmental and Molecular Mutagenesis Journal Issue: Suppl.23 Vol. 23; ISSN 0893-6692; ISSN EMMUEG
- Country of Publication:
- United States
- Language:
- English
Similar Records
Modulation of the clastogenic activity of ionizing radiation and bleomycin by the aminothiol WR-1065
The development of in vitro mutagenicity testing systems using T-lymphocytes: Progress report, November 1, 1987--May 31, 1988