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Title: Bystander and Adaptive Responses in Tissue Models exposed to Low Radiation Doses

Abstract

The overall goal is characterization of 3D tissue models that can be used for investigation of the mechanisms underlying radiation-induced bystander effect at low doses (20 cGy or less) of low LET ionizing radiation, using a unique focused soft X-ray microprobe that had been upgraded to provide a range of focused soft X-ray energies, some sufficient to penetrate 3D models (Ref DE-FG02-01ER63236). The proposed studies will include an examination of whether the passage of a single electron track can trigger bystander responses in the 3D tissue models and, if so, whether the response is altered by increased or decreased levels of oxidative stress. Our existing multi-photon/confocal in-depth microscopy techniques will be used to develop assays for damage induced within intact 3D tissue models. The working hypothesis is that organization of cells into tissues, particularly involving more than one cell type, alters expression of the radiation-induced bystander effect compared to that seen in isolated single cell types in monolayer.

Authors:
Publication Date:
Research Org.:
Gray Cancer Institute
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
896797
Report Number(s):
DOE/ER/63633-1
DOE Contract Number:
FG02-03ER63633
Resource Type:
Technical Report
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; Radiation / Bystander effect / Tissue Models

Citation Formats

Kevin M. Prise. Bystander and Adaptive Responses in Tissue Models exposed to Low Radiation Doses. United States: N. p., 2007. Web.
Kevin M. Prise. Bystander and Adaptive Responses in Tissue Models exposed to Low Radiation Doses. United States.
Kevin M. Prise. Tue . "Bystander and Adaptive Responses in Tissue Models exposed to Low Radiation Doses". United States. doi:.
@article{osti_896797,
title = {Bystander and Adaptive Responses in Tissue Models exposed to Low Radiation Doses},
author = {Kevin M. Prise},
abstractNote = {The overall goal is characterization of 3D tissue models that can be used for investigation of the mechanisms underlying radiation-induced bystander effect at low doses (20 cGy or less) of low LET ionizing radiation, using a unique focused soft X-ray microprobe that had been upgraded to provide a range of focused soft X-ray energies, some sufficient to penetrate 3D models (Ref DE-FG02-01ER63236). The proposed studies will include an examination of whether the passage of a single electron track can trigger bystander responses in the 3D tissue models and, if so, whether the response is altered by increased or decreased levels of oxidative stress. Our existing multi-photon/confocal in-depth microscopy techniques will be used to develop assays for damage induced within intact 3D tissue models. The working hypothesis is that organization of cells into tissues, particularly involving more than one cell type, alters expression of the radiation-induced bystander effect compared to that seen in isolated single cell types in monolayer.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Tue Jan 02 00:00:00 EST 2007},
month = {Tue Jan 02 00:00:00 EST 2007}
}

Technical Report:
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  • The management of the risks of exposure of people to ionizing radiation is important in relation to its uses in industry and medicine, also to natural and man-made radiation in the environment. The vase majority of exposures are at a very low level of radiation dose. The risks are of inducing cancer in the exposed individuals and a smaller risk of inducing genetic damage that can be transmitted to children conceived after exposure. Studies of these risks in exposed population studies with any accuracy above the normal levels of cancer and genetic defects unless the dose levels are high. Inmore » practice, this means that our knowledge depends very largely on the information gained from the follow-up of the survivors of the atomic bombs dropped on Japanese cities. The risks calculated from these high-dose short-duration exposures then have to be projected down to the low-dose long-term exposures that apply generally. Recent research using cells in culture has revealed that the relations hi between high- and low-dose biological damage may be much more complex than had previously been thought. The aims of this and other projects in the DOE's Low-Dose Program are to gain an understanding of the biological actions of low-dose radiation, ultimately to provide information that will lead to more accurate quantification of low-dose risk. Our project is based on the concept that the processes by which radiation induces cancer start where the individual tracks of radiation impact on cells and tissues. At the dose levels of most low-dose exposures, these events are rare and any individual cells only ''sees'' radiation tracks at intervals averaging from weeks to years apart. This contracts with the atomic bomb exposures where, on average, each cell was hit by hundreds of tracks instantaneously. We have therefore developed microbeam techniques that enable us to target cells in culture with any number of tracks, from one upwards. This approach enables us to study the biological basis of the relationship between high- and low-dose exposures. The targeting approach also allows us to study very clearly a newly recognized effect of radiation, the ''bystander effect'', which appears to dominate some low-dose responses and therefore may have a significant role in low-dose risk mechanisms. Our project also addresses the concept that the background of naturally occurring oxidative damage that takes place continually in cells due to byproducts of metabolism may play a role in treatments that modify the levels of oxidative damage, either alone or in combination with low-dose irradiation. In this project, we have used human and rodent cell lines and each set of experiments has been carried out on a single cell type. However, low-dose research has to extend into tissues because signaling between cells of different types is likely to influence the responses. Our studies have therefore also included microbeam experiments using a model tissue system that consists of an explant of a small piece of pig ureter grown in culture. The structure of this tissue is similar to that of epithelium and there it relates to the tissues in which carcinoma arises. Our studies have been able to measure bystander-induced changes in the cells growing out from the tissue fragment after it has been targeted with a few radiation tracks to mimic a low-dose exposure.« less
  • The management of the risks of exposure of people to ionizing radiation is important in relation to its uses in industry and medicine, also to natural and man-made radiation in the environment. The vase majority of exposures are at a very low level of radiation dose. The risks are of inducing cancer in the exposed individuals and a smaller risk of inducing genetic damage that can be indicate that they are low. As a result, the risks are impossible to detect in population studies with any accuracy above the normal levels of cancer and genetic defects unless the dose levelsmore » are high. In practice, this means that our knowledge depends very largely on the information gained from the follow-up of the survivors of the atomic bombs dropped on Japanese cities. The risks calculated from these high-dose short-duration exposures then have to be projected down to the low-dose long-term exposures that apply generally. Recent research using cells in culture has revealed that the relationship between high- and low-dose biological damage may be much more complex than had previously been thought. The aims of this and other projects in the DOE's Low-Dose Program are to gain an understanding of the biological actions of low-dose radiation, ultimately to provide information that will lead to more accurate quantification of low-dose risk. Our project is based on the concept that the processes by which radiation induces cancer start where the individual tracks of radiation impact on cells and tissues. At the dose levels of most low-dose exposures, these events are rare and any individual cells only ''sees'' radiation tracks at intervals averaging from weeks to years apart. This contrasts with the atomic bomb exposures where, on average, each cell was hit by hundreds of tracks instantaneously. We have therefore developed microbeam techniques that enable us to target cells in culture with any numbers of tracks, from one upwards. This approach enables us to study the biological ha sis of the relationship between high- and low-dose exposures. The targeting approach also allows us to study very clearly a newly recognized effect of radiation, the ''bystander effect'', which appears to dominate some low-dose responses and therefore may have a significant role in low-dose risk mechanisms. Our project also addresses the concept that the background of naturally occurring oxidative damage that takes place continually in cells due to byproducts of metabolism may play a role in low-dose radiation risk. This project therefore also examines how cells are damaged by treatments that modify the levels of oxidative damage, either alone or in combination with low-dose irradiation. In this project, we have used human and rodent cell lines and each set of experiments has been carried out on a single cell type. However, low-dose research has to extend into tissues because signaling between cells of different types is likely to influence the responses. Our studies have therefore also included microbeam experiments using a model tissue system that consists of an explant of a small piece of pig ureter grown in culture. The structure of this tissue is similar to that of epithelium and therefore it relates to the tissues in which carcinoma arises. Our studies have been able to measure bystander-induced changes in the cells growing out from the tissue fragment after it has been targeted with a few radiation tracks to mimic a low-dose exposure.« less
  • This project is part of the DOE research program on the biological effects of low dose and dose rate ionizing radiation. This DOE program is designed to support and conduct science that can impact the subsequent development of health risk policy for low dose radiation exposures in the US. The overall, long-term goal of this project is to increase understanding of the responses of cells to the low doses of ionizing radiation typically encountered in environmental level exposures. To achieve this objective, we couple use of a unique focused soft X-ray facility for low dose irradiation of individual cells ormore » irradiation of specific subcellular regions of cells with studies of the effects of reactive oxygen species (ROS) produced in cells. The project includes seven specific goals: (1) Determine the response of individual cells to low doses of ionizing radiation from a focused soft X-ray beam with a 250 nm diameter beam spot. (2) Determine the response of cells to ROS generated by chemical agents in a fashion that mimics the endogenous cellular generation of ROS. (3) Study the interaction between cellular oxidative processes and ionizing radiation. (4) Determine the importance of the subcellular distribution of ROS from focused soft X-rays on cellular response. (5) Determine whether damage deposited in individual cells by focused soft X-rays or by chemically-generated ROS can elicit a response in other, surrounding, untreated cells, a ''bystander'' effect. (6) Quantify the low dose response and the targets involved in the genomic instability phenotype in cells exposed to low LET radiation and the relationship with the bystander response.« less
  • This project is part of the DOE research program on the biological effects of low dose and dose rate ionizing radiation. This DOE program is designed to support and conduct science that can impact the subsequent development of health risk policy for low dose radiation exposures in the US. The overall, long-term goal of this project is to increase understanding of the responses of cells to the low doses of ionizing radiation typically encountered in environmental level exposures. To achieve this objective, we couple use of a unique focused soft X-ray facility for low dose irradiation of individual cells ormore » irradiation of specific subcellular regions of cells with studies of the effects of reactive oxygen species (ROS) produced in cells. The project includes seven specific goals: (1) Determine the response of individual cells to low doses of ionizing radiation from a focused soft X-ray beam with a 250 nm diameter beam spot. (2) Determine the response of cells to ROS generated by chemical agents in a fashion that mimics the endogenous cellular generation of ROS. (3) Study the interaction between cellular oxidative processes and ionizing radiation. (4) Determine the importance of the subcellular distribution of ROS from focused soft X-rays on cellular response. (5) Determine whether damage deposited in individual cells by focused soft X-rays or by chemically-generated ROS can elicit a response in other, surrounding, untreated cells, a ''bystander'' effect. (6) Quantify the low dose response and the targets involved in the genomic instability phenotype in cells exposed to low LET radiation and the relationship with the bystander response. (7) Develop tissue explant systems for the measurement of low dose effects in multicellular systems.« less
  • No abstract prepared.