Dimethyl sulfoxide protects against thermal and epithermal neutron-inducedcell death and mutagenesis of Chinese hamster ovary (CHO) cells

Purpose: To investigate the protective effects of dimethyl sulfoxide (DMSO) on cell killing and mutagenicity at the HPRT locus in Chinese hamster ovar y (CHO) cells against thermal and epithermal neutrons produced at the Kyoto University Research (KUR) reactor. Methods and Materials: DMSO was added to cells 15 min before irradiation an d removed 15 min after irradiation. Cells were irradiated by thermal and ep ithermal neutrons with or without boron at 10 ppm, The biological endpoint of cell survival was measured by colony formation assay, The mutagenicity w as measured by the mutant frequency in the HPRT locus, A total of 378 indep endent neutron-induced mutant clones were isolated in separate experiments, The molecular structure of HPRT mutations was determined by analysis by mu ltiples polymerase chain reaction of all nine exons, Results: The D-o values of epithermal and thermal neutrons in three differe nt modes, i.e., thermal, epithermal, and mixtures of thermal and epithermal , were 0.8-1.2 Gy, When cells were treated with DMSO, the D-o values increa sed to 1.0-2.3, especially in the absence of boron, DMSO showed a protectiv e effect against mutagenesis of the HPRT locus induced by epithermal and th ermal neutron irradiation. After DMSO treatment, the mutagenicity was decre ased, especially when the cells were irradiated in epithermal neutron mode. Molecular structure analysis indicated that total and partial deletions we re dominant and the incidence of total deletions was increased in the prese nce of boron in the thermal neutron and mixed modes. In the epithermal neut ron mode, more than half of the mutations were total deletions. When cells were treated with DMSO, the incidence of total deletions by thermal neutron irradiation with boron and epithermal irradiation decreased. Conclusions: Our results suggest that DMSO has various protective effects a gainst cytotoxic and mutagenic effects of thermal and epithermal neutrons, and that the extent of protection is reflected by the percentage of absorbe d dose distribution for each neutron irradiation mode. (C) 2000 Elsevier Sc ience Inc.