MECHANISMS OF RADIOSENSITIZATION IN BROMODEOXYURIDINE-SUBSTITUTED CELLS

The radiosensitization of exponentially-growing V79-171 cells whose DN A has been substituted by bromodeoxyuridine (BrdU) in place of thymidi ne is decreased if acetone is present during irradiation. Acetone, at a concentration of 1 mol dm-3, removes the majority of the increase in double-strand breaks (dsbs) caused by BrdU substitution, but only rem oves approximately half of the increase in cell killing. The decrease in cell radiosensitization coincides with the removal of the additiona l dsbs. The protection afforded by acetone against dsbs is assumed to be due to its ability to scavenge hydrated electrons, thought to be th e active species causing the increased DNA damage in the presence of B rdU. The residual component of BrdU radiosensitization which could not be removed by treatment with acetone may be due to either a subset of non-scavengable, lethal dsbs or the influence of BrdU on the fixation of potentially-lethal damage (Iliakis et al. 1992). Cells substituted with BrdU are not sensitized to hydroxyl radicals (from hydrogen pero xide). Also, the enhanced levels of single-strand break (ssb) and dsb production in cells substituted with BrdU arise from analogous events (i.e. increases in the yield of ssbs). These studies support the local ly multiply damaged site theory of lesion (dsb) production (Ward 1981) and, in the case of BrdU-substituted cells, the increase in dsbs appe ars to be due to the production of additional ssbs by hydrated electro ns at sites of multiple damage.