Why This Project?

Genomic instability involves the delayed formation of chromosome alterations and the delayed production of mutations in various genes. This may occur several generations after the radiation exposure. Because of the many changes that are necessary in the conversion of a normal cell into a cancer cell, it is thought that genomic instability may be an essential step in cancer development.

Project Goals:

Better understanding of how radiation can cause genomic instability.

Research Approach:

We have devised a system to measure delayed mutations caused by low doses of radiation. This involves the measurement of mutations occurring in a non-radiated reporter gene inserted into irradiated human cancer cells at various times after the radiation exposure. The induction of genomic instability in the human cells caused by the low dose of radiation is then determined by mutations occurring in the non-radiated reporter gene. For instance, if the initial radiation caused faulty synthesis of the host cell DNA as well as faulty synthesis of the reporter gene DNA, mutations would occur in the reporter gene as well as the host cell DNA. Mutations in our reporter gene are detected by a change in color of the host cell. These colored cells can then be detected and counted quickly by a method called flow cytometry. This method makes it possible to quickly evaluate large numbers of cells.

Expected Outcomes:

1. Detect the induction of genomic instability by low doses of radiation, the timing of its occurrence and its disappearance.
   
2. Determine the relative efficiency of induction of genomic instability between host cells differing in their genetic background.

Additional Information:

1. To date, the results indicate that mutations in the reporter gene can be induced by low energy radiation similar to X- rays.
   
2. We also found that mutations in the reporter gene could be caused by treatment with low concentrations of hydrogen peroxide which produce reactive oxygen species or free radicals. This indicates that the free radicals produced by radiation may cause the observed mutations, which may result in genomic instability.