Cytogenetic tests of Radiobiological Models Relating Epidemiologically Measurable Risks to Low-Dose Risks

Rainer K. Sachs

University of California, Berkeley

Why This Project

It is difficult to obtain and interpret dose-response curves for chromosome aberration to predict cancer risk response from low dose radiation. Our project develops models to do this. The doses in these models are very small compared to typical experimental doses, and even small compared to epidemiologically tractable doses.

Project Goals

1. Develop credible, experimentally-based dose-response relationships for chromosome aberrations, in the intermediate-dose range (up to 2 Gy or more) where epidemiology is feasible,
2. Develop credible, experimentally based dose-response models for chromosome aberrations in the more relevant low-dose range (less than 0.1 Gy).
3. Relate chromosome damage to radiation-induced cancer.

Research Approach

By studying molecular mechanisms relevant to low doses and low dose-rates quantitatively, and comparing with endogenous or background damage, we are working toward credible cancer risk estimation. Exchange-type chromosome aberrations, are biologically complex endpoints, characteristic of ionizing radiation damage/repair/ misrepair pathways, and are generally considered causes of, or at least useful endpoints, for predicting radiation carcinogenesis. Recent work estimates risks of very specific cancers that are caused by, or at least very strongly associated with, specific chromosome translocations, such as those found in leukemia (which results in the fusion gene BCR-ABL) or in thyroid cancer (to produce the H4-RET gene).

Expected Outcomes

1. This focus on specific aberrations cancer types allows the use of geometric information about chromosome locations in the non-dividing nucleus of the cell and information about aberration mechanisms to give numerical risk estimates based on fundamental biophysics.
2. Risk estimates can be determined for different radiation types.

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