Radiation-induced bystander effect following hypo- fraction technique of grid therapy by use of sensitive molecular markers

Document Type: Conference Proceedings

Authors

1 Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran, Iran

2 Radiation Oncology Department, Cancer institute, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

4 Department of Bioscience and Biotechnology, Malek-Ashtar University of Technology, Tehran, Iran

5 Department of medical genetics, Medical biotechnology institute, National institute of genetic engineering and biotechnology, Tehran, Iran

Abstract

Introduction:
Radiation-induced bystander effect (RIBE) is a well-known response associated with the
induction of radiation effects in non-irradiated cells via signaling of hit ones. As this so-called phenomenon has been largely investigated in low dose levels, few studies focused on higher dose levels such as grid therapy. Grid therapy or spatially fractionated grid radiation therapy (SFGRT) is a hypo-fraction technique for treatment of advance and bulky malignant tumors. Different advantages of SFGRT including minimal skin side effects and effective tumor
control despite the small portion of exposure based on grid pattern, made it as an attractive
therapy approach. SO the aim of this research was determination of bystander response
following the mentioned therapy method.
Materials and Methods:
In this study, we evaluated RIBE via distinct protocols of media transfer and cell to cell
contact following grid therapy. Two different human cell lines (SCC and Hela) were
irradiated by challenging dose of 10 Gy with available grid block attached to the linac head
in single radiation field. Irradiation with Grid pattern of 145 circular fields, 13mm in
diameter with 17mm center to center distance created the cell to cell contact of directly
irradiated and bystander cells. To fulfill the aim of media transfer of our study, bystander
cells or grid adjacent cells were irradiated by 1.5Gy receiving the conditioned medium of hit
cells. Based on RIBE DNA damage and DSB formation, phosphorylation of histone H2AX
could be the novel sensitive marker for early detection of DSBs in intact cells. So Bystander
effect has been assessed by use of sensitive molecular biomarkers of gamma h2ax as well as
gene expression.
Results& Conclusion:
Our results indicated the occurrence of RIBE following the high dose hypo-fraction technique
of grid therapy and emphasized on the role of sensitive molecular biomarkers in bystander
DNA damage mechanism.

Keywords