Biological Sciences Division
Low-dose work highlighted in three journal articles
Results from work at Pacific Northwest National Laboratory (PNNL) sponsored by the U.S. Department of Energy's Low-Dose Radiation Program are described in three articles in the November 2005 issue of Radiation Research.
One article features work done by PNNL to determine whether low doses of low-linear energy transfer (LET) radiation induce shedding of bioactive molecules. Shedding, the release of cell surface proteins by regulated proteolysis, is a general cellular response to injury and generates signaling molecules such as growth factors and cytokines. Using a mass spectrometry-based global proteomics method, the PNNL team analyzed media for shed proteins secreted by irradiated human mammary epithelial cells. Several hundred proteins were identified; however, no changes in abundance attributable to radiation exposure were observed. The results showed that the proteomic-based approach developed at PNNL has the sensitivity to identify the kinds of proteins believed to be released after low-dose radiation exposure, but that improvements are needed in the ability to detect the small abundance changes associated with this type of insult. The authors include David L. Springer, Joshua N. Adkins, and Loel E. Kathmann, PNNL; and John H. Miller, Washington State University.
The other two articles feature microbeam studies, a powerful technique for understanding the interaction of ionizing radiation with cells and tissues. The first paper represents a technical advance and describes the development and characterization of a low-cost, variable-energy, low-linear energy transfer (LET) electron microbeam. This device, which was constructed at PNNL, uses energetic electrons to mimic radiation damage produced by gamma and X rays. The microbeam can access lower regions of the LET spectrum, similar to conventional X-ray or 60Co gamma-ray sources. Authors are Marianne B. Sowa, Mark K. Murphy, Joseph C. McDonald, Daniel J. Strom, and Gregory A. Kimmel, PNNL; and John H. Miller, WSU.
A related article describes use of the low-LET electron microbeam to selectively expose human diploid fibroblasts to different parts of the energetic electron tracks. The low-energy ends of electrically charged accelerated particle tracks have long been hypothesized to be the dominant source of damage when low-LET radiation interacts with biological samples. Until recently, it has been difficult to directly assess the role of the track terminus in the observed biological response. Using a pulsed electron beam, the PNNL team investigated the incident electron energy dependence on micronuclei formation in fibroblasts after nontargeted irradiations at 25 and 80 keV. They found that 25 keV electrons are more effective than 80 keV electrons at producing biological damage for a given dose. The results demonstrated the induction of micronuclei as a function of incident electron energy and support the hypothesis that the electron track end is responsible for the biological damage occurring in the cell. Authors are Marianne B. Sowa, Loel E. Kathmann, Brooke A. Holben, Brian D. Thrall, and Greg A. Kimmel.
The journal articles can be accessed on the BioOne™ website.
Springer DL, M Ahram, JN Adkins, LE Kathmann, and JH Miller. 2005. "Characterization of Medium Conditioned by Irradiated Cells Using Proteome-Wide, High-Throughput Mass Spectrometry." Radiation Research 164(5):651-654. DOI:10.1667/RR3457.1.
Sowa MB, LE Kathmann, BA Holben, BD Thrall, and GA Kimmel. 2005. "Low-LET Microbeam Investigation of the Track-End Dependence of Electron-Induced Damage in Normal Human Diploid Fibroblasts." Radiation Research 164(5):677-679. DOI:10.1667/RR3464.1.
Sowa MB, MK Murphy, JH Miller, JC McDonald, DJ Strom, and GA Kimmel. 2005. "A Variable-Energy Electron Microbeam: A Unique Modality for Targeted Low-LET Radiation." Radiation Research 164(5):695-700. DOI:10.1667/RR3463.1.