Purpose: Wortmannin, a phosphatidylinositol 3-kinase inhibitor, has been found to inhibit DNA-dependent protein kinase (DNA-PKcs) and to be an efficient radiosensitizer. We investigated the radiosensitizing effect of wortmannin on cell killing by thermal neutrons and the occurrence of mutations at the HPRT locus of CHO cells.
Materials and methods: Wortmannin was added to cells at a final concentration of 20 microM two hours before irradiation. Cells were irradiated with thermal neutrons. The biological end point of cell survival was measured by colony formation assay. Mutagenicity was calculated from the mutation frequency at the HPRT locus.
Results: Wortmannin promoted cell death following thermal neutron irradiation especially in the absence of boron. However, mutagenicity was decreased by the wortmannin treatment.
Conclusion: Our results suggest that the inhibition of DNA-PKcs by wortmannin would be an effective radiosensitizer for BNCT and might bring about a reduction in the frequency of mutation by blocking the mis-joining of DNA damage during the repair process.