Evidence for Pronounced Bystander Effects Caused by Nonuniform Distributions of Radioactivity using a Novel Three-Dimensional Tissue Culture Model

Abstract

A new in vitro multicellular cluster model has been developed to assess the impact of nonuniform distributions of radioactivity on the biological response of mammalian cells, and the relative importance of bystander effects compared to conventional radiation effects. Chinese hamster V79 cells are labeled with tritiated thymidine $([{}^{3}{\rm H}]{\rm dThd})$ , mixed with unlabeled V79 cells, and centrifuged gently to form multicellular clusters about 1.6 mm in diameter. The short range of the3 H β particles effectively allows only self-irradiation of labeled cells and no cross-irradiation of unlabeled cells. The percentage of labeled cells is controlled precisely by varying the number of labeled cells mixed with unlabeled cells prior to assembling the cluster. The clusters are assembled in the absence or presence of 100 μM lindane, a chemical that is known to inhibit formation of gap junctions. After the clusters are maintained at 10.5°C for 72 h, the cells are dispersed and plated for...