Assessment of The Dose-Response Relationship of
Radiation-Induced Bystander Effect in Two
Cell Lines Exposed to High Doses of
Ionizing Radiation (6 and 8 Gy)

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Objective

The dose-response relationship of radiation-induced bystander effect (RIBE) is controversial at high dose levels. The aim of the present study is to assess RIBE at high dose levels by examination of different endpoints.

Materials and Methods

This experimental study used the medium transfer technique to induce RIBE. The cells were divided into two main groups: QU-DB cells which received medium from autologous irradiated cells and MRC5 cells which received medium from irradiated QU-DB cells. Colony, MTT, and micronucleus assays were performed to quantify bystander responses. The medium was diluted and transferred to bystander cells to investigate whether medium dilution could revive the RIBE response that disappeared at a high dose.

Results

The RIBE level in QU-DB bystander cells increased in the dose range of 0.5 to 4 Gy, but decreased at 6 and 8 Gy. The Micronucleated cells per 1000 binucleated cells (MNBN) frequency of QU-DB bystander cells which received the most diluted medium from 6 and 8 Gy QU-DB irradiated cells reached the maximum level compared to the MNBN frequency of the cells that received complete medium (P<0.0001). MNBN frequency of MRC5 cells which received the most diluted medium from 4 Gy QU-DB irradiated cells reached the maximum level compared to MNBN frequency of cells that received complete medium (P<0.0001).

Conclusion

Our results showed that RIBE levels decreased at doses above 4 Gy; however, RIBE increased when diluted conditioned medium was transferred to bystander cells. This finding confirmed that a negative feedback mechanism was responsible for the decrease in RIBE response at high doses. Decrease of RIBE at high doses might be used to predict that in radiosurgery, brachytherapy and grid therapy, in which high dose per fraction is applied, normal tissue damage owing to RIBE may decrease.

Related collections

Most cited references 16

Record: found
Abstract: found
Article: not found

Long-term consequences of radiation-induced bystander effects depend on radiation quality and dose and correlate with oxidative stress.

Manuela Buonanno, Edouard I Azzam, Willem M de Vos … (2011)

Widespread evidence indicates that exposure of cell populations to ionizing radiation results in significant biological changes in both the irradiated and nonirradiated bystander cells in the population. We investigated the role of radiation quality, or linear energy transfer (LET), and radiation dose in the propagation of stressful effects in the progeny of bystander cells. Confluent normal human cell cultures were exposed to low or high doses of 1GeV/u iron ions (LET ∼ 151 keV/µm), 600 MeV/u silicon ions (LET ∼ 51 keV/µm), or 1 GeV protons (LET ∼ 0.2 keV/µm). Within minutes after irradiation, the cells were trypsinized and co-cultured with nonirradiated cells for 5 h. During this time, irradiated and nonirradiated cells were grown on either side of an insert with 3-µm pores. Nonirradiated cells were then harvested and allowed to grow for 20 generations. Relative to controls, the progeny of bystander cells that were co-cultured with cells irradiated with iron or silicon ions, but not protons, exhibited reduced cloning efficiency and harbored higher levels of chromosomal damage, protein oxidation and lipid peroxidation. This correlated with decreased activity of antioxidant enzymes, inactivation of the redox-sensitive metabolic enzyme aconitase, and altered translation of proteins encoded by mitochondrial DNA. Together, the results demonstrate that the long-term consequences of the induced nontargeted effects greatly depend on the quality and dose of the radiation and involve persistent oxidative stress due to induced perturbations in oxidative metabolism. They are relevant to estimates of health risks from exposures to space radiation and the emergence of second malignancies after radiotherapy. © 2011 by Radiation Research Society

0 comments Cited 46 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Radiation-induced biologic bystander effect elicited in vitro by targeted radiopharmaceuticals labeled with alpha-, beta-, and auger electron-emitting radionuclides.

K. Tan, Robert J Mairs, Michael Zalutsky … (2006)

Recent studies have shown that indirect effects of ionizing radiation may contribute significantly to the effectiveness of radiotherapy by sterilizing malignant cells that are not directly hit by the radiation. However, there have been few investigations of the importance of indirect effects in targeted radionuclide treatment. Our purpose was to compare the induction of bystander effects by external beam gamma-radiation with those resultant from exposure to 3 radiohaloanalogs of metaiodobenzylguanidine (MIBG): (131)I-MIBG (low-linear-energy-transfer [LET] beta-emitter), (123)I-MIBG (potentially high-LET Auger electron emitter), and meta-(211)At-astatobenzylguanidine ((211)At-MABG) (high-LET alpha-emitter). Two human tumor cell lines-UVW (glioma) and EJ138 (transitional cell carcinoma of bladder)-were transfected with the noradrenaline transporter (NAT) gene to enable active uptake of MIBG. Medium from cells that accumulated the radiopharmaceuticals or were treated with external beam radiation was transferred to cells that had not been exposed to radioactivity, and clonogenic survival was determined in donor and recipient cultures. Over the dose range 0-9 Gy of external beam radiation of donor cells, 2 Gy caused 30%-40% clonogenic cell kill in recipient cultures. This potency was maintained but not increased by higher dosage. In contrast, no corresponding saturation of bystander cell kill was observed after treatment with a range of activity concentrations of (131)I-MIBG, which resulted in up to 97% death of donor cells. Cellular uptake of (123)I-MIBG and (211)At-MABG induced increasing recipient cell kill up to levels that resulted in direct kill of 35%-70% of clonogens. Thereafter, the administration of higher activity concentrations of these high-LET emitters was inversely related to the kill of recipient cells. Over the range of activity concentrations examined, neither direct nor indirect kill was observed in cultures of cells not expressing the NAT and, thus, incapable of active uptake of MIBG. Potent toxins are generated specifically by cells that concentrate radiohalogenated MIBG. These may be LET dependent and distinct from those elicited by conventional radiotherapy.

0 comments Cited 25 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Cellular response to modulated radiation fields.

Erica McKenzie, N Suchowerska, M. Jackson … (2007)

Cell survival following exposure to spatially modulated beams, as created by intensity-modulated radiotherapy (IMRT), is investigated. In vitro experiments were performed using malignant melanoma cells (MM576) exposed to a therapeutic megavoltage photon beam. We compared cell survival in modulated fields with cell survival in uniform control fields. Three different spatial modulations of the field were used: a control 'uniform' field in which all cells in a flask were uniformly exposed; a 'quarter' field in which 25% of cells at one end of the flask were exposed and a 'striped' field in which 25% of cells were exposed in three parallel stripes. The cell survival in both the shielded and unshielded regions of the modulated fields, as determined by a clonogenic assay, were compared to the cell survival in the uniform field. We have distinguished three ways in which cell survival is influenced by the fate of neighbouring cells. The first of these (type I effect) is the previously reported classical Bystander effect, where cell survival is reduced when communicating with irradiated cells. We find two new types of Bystander effect. The type II effect is an observed increase in cell survival when nearby cells receive a lethal dose. The type III effect is an increase in the survival of cells receiving a high dose of radiation, when nearby cells receive a low dose. These observations of the Bystander effects emphasize the need for improved radiobiological models, which include communicated effects and account for the effects of modulated dose distribution.

0 comments Cited 19 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Cell J

Journal ID (iso-abbrev): Cell J

Journal ID (publisher-id): Royan Institute

Title: Cell Journal (Yakhteh)

Publisher: Royan Institute

ISSN (Print): 2228-5806

ISSN (Electronic): 2228-5814

Publication date (Print): Autumn 2017

Publication date (Electronic): 19 August 2017

Volume: 19

Issue: 3

Pages: 434-442

Affiliations

[1 ]Medical Physics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

[2 ]Department of Medical Physics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

[3 ]Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

[4 ]Department of Medical Physics, Omid Hospital, Mashhad, Iran

Author notes

[*Corresponding Address: ]P.O. BOX: 917794-8564Department of Medical PhysicsSchool of MedicineMashhad University of Medical Sciences MashhadIran Email: soleymanifardsh@ 123456mums.ac.ir

Article

Other ID: Cell-J-19-434

DOI: 10.22074/cellj.2017.4343

PMC ID: 5570408

PubMed ID: 28836405

SO-VID: 353cf755-95e3-4728-afe9-18299f5a93b1

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 7 June 2016

Date accepted : 11 September 2016

Custom metadata

Citation Bahreyni Toossi MT, Khademi S, Azimian H, Mohebbi Sh, Soleymanifard Sh. Assessment of the dose-response relationship of radiation-induced bystander effect in two cell lines exposed to high doses of lonizing radiation (6 and 8 Gy). Cell J. 2017; 19(3): 434-442. doi: 10.22074/cellj.2017.4343.

Keywords: dose-response relationship,mrc5 cell line,radiotherapy

Data availability:

Keywords: dose-response relationship, mrc5 cell line, radiotherapy