Bystander cell proliferation is modulated by the number of adjacent cells that were exposed to ionizing radiation.
BACKGROUND
Direct cell-to-cell contact appears to be a prerequisite for the proliferative response of bystander WB-F344 cells co-cultured with irradiated cells; however, neither gap junctional intercellular communication nor long-range factors released into the medium appear to be involved (Cytometry 2003;56A:71-80). The present work investigated whether the proliferative bystander response depends on the number of irradiated cells (cells exposed to external gamma-rays or cells exposed to short-range beta-particles emitted by DNA-incorporated (3)H-thymidine) that are adjacent to unirradiated bystander cells.


METHODS
Subconfluent monolayers of rat liver epithelial cells (WB-F344) were incubated in the presence of (methyl-(3)H)thymidine at a concentration of 5.8 kBq/ml for 18 h. Radiolabeled cells containing 0.7 x 10(-3) Bq/cell (absorbed dose: 0.14 Gy) were plated together with unlabeled cells in proportions of 6% and 94%, 12% and 88%, 25% and 75%, 50% and 50%, and 75% and 25%, respectively, keeping constant the total number of plated cells. In a parallel experiment, cells acutely exposed to 5 Gy of (137)Cs gamma-rays were plated with unirradiated cells in the same proportions. In both experiments, cells were co-cultured for 24 h followed by a flow cytometric study of their proliferation. The two cell populations in the co-cultures were distinguished by staining one population with carboxyfluorescein diacetate, succinimidyl ester, which metabolizes intracellularly.


RESULTS
Increasing the fraction of irradiated cells relative to unirradiated bystander cells led to an increase in proliferation of bystander cells. Specifically, in co-cultures in which irradiated cells were initially mixed with unirradiated cells in proportions of 50% and 50% and of 75% and 25%, respectively, bystander cells showed a statistically significant increase of their proliferation compared with the controls.


CONCLUSIONS
The proliferative response of WB-F344 bystander cells is modulated by the number of adjacent cells that are exposed to ionizing radiation from external gamma-rays or intracellularly emitted (3)H beta-particles.
Gerashchenko
Bogdan I
BI
Department of Radiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103-2714, USA.
Howell
Roger W
RW
D000818:Animals; D024201:Bystander Effect; D002452:Cell Count; D002460:Cell Line; D049109:Cell Proliferation / Q000528:radiation effects*; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000166:cytology / Q000528:radiation effects*; D005434:Flow Cytometry; D005720:Gamma Rays; D007365:Intercellular Junctions / Q000528:radiation effects*; D008099:Liver / Q000166:cytology; D051381:Rats; D014316:Tritium
D014316:Tritium