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-[At-211]astato-2'-de oxyuridine ((211)AtdU, exposure from DNA-incorporated activity) or wit h [At-211]astatide (At-211(-), exposure from extracellular activity), and DNA-incorporated activity was determined. The (211)AtdU content in cellular DNA increased as a function of extracellular concentration. Incorporation of At-211(-) was less than 1% of that of (211)AtdU. Afte r exposure, cells were frozen in the presence of 10% DMSO. One month l ater, survival was determined by the colony-forming assay, and DNA dou ble-strand breaks (DSBs) were measured by the neutral elution method ( pH 9.6). The survival curve for (211)AtdU was biphasic (D-37 = 2.8 dec ays per cell), reflecting killing of At-211-DNA-labeled cells and of u nlabeled cells irradiated by At-211 in neighboring labeled cells. The toxicity of At-211(-) decaying outside the cell (30-min exposure) was negligible. Analysis of the survival curve produced a D-0 of 1.3 decay s/cell for At-211-labeled cells. The yield of DSBs from the decay of D NA-incorporated At-211 was compared with that from DNA-incorporated I- 122. Each decay of At-211 produced at least 10 times the number of DSB s as that obtained per I-125 decay. The extreme radiotoxicity of DNA-i ncorporated (211)AtdU seems to be associated with considerable damage to the mammalian cell genome. (C) 1998 by Radiation Research Society.