Use of a State-Vector Model of Radiation Carcinogenesis to Integrate Information from In vitro, In vivo, Epidemiological and Physiological Studies

Douglas Crawford-Brown
douglas_crawford-brown@unc.edu
University of North Carolina at Chapel Hill
Website: http://www.sph.unc.edu/envr/facstaff/?fuseaction=profile_detail&subject=envr&profile
_id=1219&class=FACULTY,STAFF&dropnull=1

Why this Project?

To improve predictions with respect to dose-response data on in vitro oncogenic transformation.

Project Goals

To assess sensitivity of the model to incorporation of new information on biological processes, including background transformation, compensatory proliferation and bystander cell-killing effect.

Experimental Approach

1. To adjust parameters with an optimization method.
2. To determine local and global sensitivity to each introduced parameter.

Expected Outcomes

The extended model yields reasonably good approximations to the data on in vitro transformation (at least those data used in this project). A plateau observed in the data at low doses is reproduced well and a dose-dependent increase above 1 Gy is predicted. Parameter value optimization suggested the existence of an overall protective, rather than detrimental, bystander cell-killing effect.