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

TY - JOUR

T1 - Bystander cell proliferation is modulated by the number of adjacent cells that were exposed to ionizing radiation

AU - Gerashchenko, Bogdan I.

AU - Howell, Roger W.

PY - 2005/7

Y1 - 2005/7

N2 - 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.

AB - 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.

KW - Adjacent cells

KW - Beta particles

KW - Bystander cells

KW - Co-culture

KW - Flow cytometry

KW - Gamma rays

KW - H-3

KW - Proliferation ratio

KW - Radiation

KW - Thymidine

KW - Tritium

UR - https://www.scopus.com/pages/publications/20944439880

UR - https://www.scopus.com/pages/publications/20944439880#tab=citedBy

U2 - 10.1002/cyto.a.20150

DO - 10.1002/cyto.a.20150

M3 - Article

C2 - 15915508

SN - 1552-4922

VL - 66

SP - 62

EP - 70

JO - Cytometry Part A

JF - Cytometry Part A

IS - 1

ER -