Low-Dose Studies with Focused X-rays in Cell and Tissue Models: Mechanisms of Bystander and Genomic Instability Responses

Michael, Barry D. ; Held, Kathryn D.

Gray Laboratory Cancer Research Trust

关键词: 63 Radiation, Thermal, And Other Environmental Pollutant Effects On Living Organisms And Biological Materials;    Research Programs;    Subcellular Distribution;    Irradiation;    Oxygen;   

DOI  :  10.2172/833478
RP-ID  :  EMSP-69980--2001
RP-ID  :  FG07-99ER62874
RP-ID  :  833478

美国|英语

来源: UNT Digital Library

【 摘 要 】

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 or 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.