Bystander effects caused by nonuniform distributions of DNA-incorporated I-125

A three-dimensional tissue culture model was used to investigate the biolog ical effects of nonuniform distributions of DNA-incorporated I-125 in mamma lian cells. Chinese hamster V79 cells were labeled with I-125-iododeoxyurid ine, mixed with unlabeled cells, and multicellular clusters (similar to 1.7 mm in diameter) were formed by gentle centrifugation. The highly localized energy deposition caused by I-125 decays results in very high equivalent d oses delivered to the labeled cells and low equivalent doses delivered to t he unlabeled cells. The clusters were assembled and then maintained at 10.5 degreesC for 72 h to allow I-125 decays to accumulate, dismantled, and the cells were plated for colony formation. When 100% of the cells were labele d, the survival fraction was exponentially dependent on the mean radioactiv ity per labeled cell. A two-component exponential response was observed whe n either 50 or 10% of the cells were labeled. These experimental data, coup led with theoretical dosimetry calculations, indicate that bystander effect s play an important role in the killing of unlabeled cells when nonuniform distributions of DNA-incorporated I-125 are present. (C) 2001 Elsevier Scie nce Ltd. All rights reserved.