Mechanisms of radiosensitization in iododeoxyuridine-substituted cells.
The radiosensitization caused by iododeoxyuridine (IdU)-substitution of thymidine in V79-171 cells is decreased by the presence of acetone during irradiation. Acetone, at 1 mol dm-3, removes almost all the increase in double strand breaks (dsbs) caused by IdU substitution, but removes only about two-thirds of the enhancement in killing. Similar observations were made with BrdU-substituted cells. The decrease in cell radiosensitization coincides with the removal of the additional dsbs. The protection afforded by acetone is assumed to be due to its scavenging of hydrated electrons, thought to be the active species causing enhanced DNA damage in the presence of halogenated pyrimidines. The residual component of IdU radiosensitization, which could not be removed by treatment with acetone, is manifest largely as a shoulder effect (Dq) and may be due to either a subset of non-scavengable, lethal dsbs and/or the influence of IdU on the fixation of potentially lethal damage. This study further demonstrates that halogenated pyrimidine-mediated radiosensitization consists of at least distinct components each associated with a different phenomenon.
Jones
G D
GD
Department of Radiology-0610, University of California, San Diego, La Jolla 92093-0610, USA.
Ward
J F
JF
Limoli
C L
CL
Moyer
D J
DJ
Aguilera
J A
JA
D000096:Acetone / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D004249:DNA Damage; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D007065:Idoxuridine / Q000378:metabolism* / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects* / Q000502:physiology*; D013936:Thymidine / Q000378:metabolism
D000096:Acetone; D004247:DNA; D007065:Idoxuridine; D013936:Thymidine