Bystander cell proliferation is modulated by the number of adjacent cells that were exposed to ionizing radiation

Bogdan I. Gerashchenko, Roger W. Howell

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


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 γ-rays or cells exposed to short-range β-particles emitted by DNA-incorporated 3H-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-3H)thymidine at a concentration of 5.8 kBq/ml for 18 h. Radiolabeled cells containing 0.7 × 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 137Cs γ-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 γ-rays or intracellularly emitted 3H β-particles.

Original languageEnglish (US)
Pages (from-to)62-70
Number of pages9
JournalCytometry Part A
Issue number1
StatePublished - Jul 2005

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology


  • Adjacent cells
  • Beta particles
  • Bystander cells
  • Co-culture
  • Flow cytometry
  • Gamma rays
  • H-3
  • Proliferation ratio
  • Radiation
  • Thymidine
  • Tritium

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