Survival and DNA damage in Chinese hamster V79 cells exposed to alpha particles emitted by DNA-incorporated astatine-211.
Asynchronous Chinese hamster V79 lung fibroblasts were incubated at 37 degrees C for 30 min with the thymidine analog 5-[211At]astato-2'-deoxyuridine (211AtdU, exposure from DNA-incorporated activity) or with [211At]astatide (211At-, exposure from extracellular activity), and DNA-incorporated activity was determined. The 211AtdU content in cellular DNA increased as a function of extracellular concentration. Incorporation of 211At- was less than 1% of that of 211AtdU. After exposure, cells were frozen in the presence of 10% DMSO. One month later, survival was determined by the colony-forming assay, and DNA double-strand breaks (DSBs) were measured by the neutral elution method (pH 9.6). The survival curve for 211AtdU was biphasic (D37 = 2.8 decays per cell), reflecting killing of 211At-DNA-labeled cells and of unlabeled cells irradiated by 211At in neighboring labeled cells. The toxicity of 211At- decaying outside the cell (30-min exposure) was negligible. Analysis of the survival curve produced a D0 of 1.3 decays/cell for 211At-labeled cells. The yield of DSBs from the decay of DNA-incorporated 211At was compared with that from DNA-incorporated 125I. Each decay of 211At produced at least 10 times the number of DSBs as that obtained per 125I decay. The extreme radiotoxicity of DNA-incorporated 211AtdU seems to be associated with considerable damage to the mammalian cell genome.
Walicka
M A
MA
Department of Radiology, Harvard Medical School, Boston, Massachusetts 02115-5729, USA.
Vaidyanathan
G
G
Zalutsky
M R
MR
Adelstein
S J
SJ
Kassis
A I
AI
D000818:Animals; D001246:Astatine / Q000493:pharmacokinetics*; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured / Q000378:metabolism / Q000528:radiation effects; D003114:Colony-Forming Units Assay; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D007065:Idoxuridine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
C098409:5-astato-2'-deoxyuridine; D004247:DNA; D007065:Idoxuridine; D001246:Astatine