Mechanisms of radiosensitization in bromodeoxyuridine-substituted cells.
The radiosensitization of exponentially-growing V79-171 cells whose DNA has been substituted by bromodeoxyuridine (BrdU) in place of thymidine 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 removes approximately half of the increase in cell killing. The decrease in cell radiosensitization coincides with the removal of the additional dsbs. The protection afforded by acetone against dsbs is assumed to be due to its ability to scavenge hydrated electrons, thought to be the active species causing the increased DNA damage in the presence of BrdU. The residual component of BrdU radiosensitization which could not be removed by treatment with acetone may be due to either a subset of nonscavengable, 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 peroxide). 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 locally multiply damaged site theory of lesion (dsb) production (Ward 1981) and, in the case of BrdU-substituted cells, the increase in dsbs appears to be due to the production of additional ssbs by hydrated electrons at sites of multiple damage.
Webb
C F
CF
Department of Radiology, University of California, San Diego, La Jolla 92093-0610.
Jones
G D
GD
Ward
J F
JF
Moyer
D J
DJ
Aguilera
J A
JA
Ling
L L
LL
D000096:Acetone / Q000494:pharmacology*; D001973:Bromodeoxyuridine; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA; D011836:Radiation Tolerance / Q000187:drug effects / Q000502:physiology*; D013936:Thymidine
D000096:Acetone; D004247:DNA; D001973:Bromodeoxyuridine; D013936:Thymidine