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Non-Invasive Early Detection and Molecular Analysis of Low X-Ray Dose Effects in the Lens.


DE141136122

Publication Date 2013
Personal Author Goldstein, L.
Page Count 8
Abstract This is the Final Progress Report for DOE-funded research project DE- SC0002213 titled Non-invasive Early Detection and Molecular Analysis of Low X-ray Dose Effects in the Lens. The project focuses on the effects of low-linear energy transfer (LET) radiation on the ocular lens. The lens is an exquisitely radiosensitive tissue with a highly-ordered molecular structure that is amenable to non-invasive optical study from the periphery. These merits point to the lens as an ideal target for laser-based molecular biodosimetry (MBD). Following exposure to different types of ionizing radiations, the lens demonstrates molecular changes (e.g., oxidation, racemization, crosslinkage, truncation, aggregation, etc.) that impact the structure and function of the long-lived proteins in the cytosol of lens fiber cells. The vast majority of proteins in the lens comprise the highly-ordered crystalline. These highly conserved lens proteins are amongst the most concentrated and stable in the body. Once synthesized, the crystalline are retained in the fiber cell cytoplasm for life. Taken together, these properties point to the lens as an ideal system for quantitative in vivo MBD assessment using quasi-elastic light scattering (QLS) analysis. In this project, we deploy a purpose-designed non-invasive infrared laser QLS instrument as a quantitative tool for longitudinal assessment of pre-cataractous molecular changes in the lenses of living mice exposed to low-dose low-LET radiation compared to non-irradiated sham controls. We hypothesize that radiation exposure will induce dose-dependent changes in the molecular structure of matrix proteins in the lens. Mechanistic assays to ascertain radiation-induced molecular changes in the lens focus on protein aggregation and gene/protein expression patterns. We anticipate that this study will contribute to our understanding of early molecular changes associated with radiation-induced tissue pathology. This study also affords potential for translational development of molecular biodosimetry instrumentation to assess human exposure to mixed radiation fields.
Keywords
  • Molecular analysis
  • Radiation doses
  • Lenses
  • Detection
  • Energy transfer
  • Eye(Anatomy)
  • Light scattering
  • Optical systems
  • Proteins
  • Radiation exposure
  • Research project
Source Agency
  • Technical Information Center Oak Ridge Tennessee
NTIS Subject Category
  • 57E - Clinical Medicine
  • 57V - Radiobiology
Corporate Authors Tufts Univ., Boston, MA. School of Medicine.; Department of Energy, Washington, DC.
Supplemental Notes Sponsored by Department of Energy, Washington, DC.
Document Type Technical Report
NTIS Issue Number 201502
Contract Number
  • DE-SC0002213
Non-Invasive Early Detection and Molecular Analysis of Low X-Ray Dose Effects in the Lens.
Non-Invasive Early Detection and Molecular Analysis of Low X-Ray Dose Effects in the Lens.
DE141136122

  • Molecular analysis
  • Radiation doses
  • Lenses
  • Detection
  • Energy transfer
  • Eye(Anatomy)
  • Light scattering
  • Optical systems
  • Proteins
  • Radiation exposure
  • Research project
  • Technical Information Center Oak Ridge Tennessee
  • 57E - Clinical Medicine
  • 57V - Radiobiology
  • DE-SC0002213
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