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Induction of Genomic Instability in vivo by Low Doses of 137Cs gamma rays

Kanokporn Noy Rithidech, Ph.D.
SUNY at Stony Brook

Why This Project

Genomic instability is an important step in radiation-induced cancer. We will investigate one potential repair mechanism involved in radiation-induced genomic instability.

Project Goals

  1. Determine if low doses of low-LET radiation can produce genomic instability, an important step in changing normal cells into cancer cells
  2. Determine the mechanisms involved in the induction of genomic instability by defining the radiation-related changes in genetic and biochemical pathways
  3. Establish whether radiation-induced genomic instability, measured as delayed chromosome instability, is related to the level of normal DNA repair

Experimental Approach

Studies will be conducted using three different strains of mice with different abilities to repair-radiation induced DNA damage. These strains of mice are: a) (C57BL/6J mice) high level of DNA repair, b) (BALB/cJ mice) intermediate level of DNA repair, and c) (scid mice) an extremely low level of DNA repair. The frequency and type of chromosome aberrations will be measured in bone marrow cells using modern molecular genetic techniques. These techniques make it possible to identify each chromosome and location of the radiation-induced chromosome change. Chromosome damage will be measured at different times, from one hour up to several months following radiation. At 1 and 4 hr following radiation, DNA-PKcs kinase activity and the activation of nuclear factor-kappa B (NF-kB). DNA-PK associated with repair of DNA double strand breaks will also be quantified in bone marrow cells. Specifically these are is involved in DNA repair and NF-kB helps regulate expression of a number of important radiation induced repair genes. Chromosome damage will be compared between the different strains of mice and related to the levels of these enzymes.

Expected Outcomes

  1. Determine how changes in gene expression related to NF-kB and DNA-PKc activation impacts genomic instability
  2. Understand some of the genetic and biochemical pathways involved during the induction of genomic instability
  3. Link radiatioin-induced physical changes, chromosome aberration, to a biochemical process involved in DNA repair.
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