Biological response to nonuniform distributions of (210)Po in multicellular clusters.

Radionuclides are distributed nonuniformly in tissue. The present work examined the impact of nonuniformities at the multicellular level on the lethal effects of (210)Po. A three-dimensional (3D) tissue culture model was used wherein V79 cells were labeled with (210)Po-citrate and mixed with unlabeled cells, and multicellular clusters were formed by centrifugation. The labeled cells were located randomly in the cluster to achieve a uniform distribution of radioactivity at the macroscopic level that was nonuniform at the multicellular level. The clusters were maintained at 10.5 degrees C for 72 h to allow alpha-particle decays to accumulate and then dismantled, and the cells were seeded for colony formation. Unlike typical survival curves for alpha particles, two-component exponential dose-response curves were observed for all three labeling conditions. Furthermore, the slopes of the survival curves for 100, 10 and 1% labeling were different. Neither the mean cluster absorbed dose nor a semi-empirical multicellular dosimetry approach could accurately predict the lethal effects of (210)Po-citrate.