For the population at large, the hazards due to biologically active agents in our environment--or associated with health services--are expected to result from low doses delivered over protracted periods. The hazards of main concern are those connected with cell inactivation, mutation, transformation, and altered differentiation. To estimate the degree of risk, it is customary to assume that the effect follows a linear or """"""""single-hit"""""""" dose dependence whose rate may be inferred usually from an extrapolation to zero dose from effects produced by high doses delivered at high dose rates. Connected with the assumption of linearity is the implicit assumption that the magnitude of an effect is independent of the rate of dose delivery. This assumption comes from the conventional application of target theory, i.e., a single absorption event in the sensitive target produces the effect. As a consequence, sub-effective events are not registered and hence, biochemical/biological processes during or between exposures cannot modify the degree of effect. However, target theory as conventionally applied is only a limiting solution of a more general relationship according to which linearity also results if only a (dose-independent) fraction of the absorption events in the target is effective. Consequently bio-chemical/biological processes which occur during a protracted exposure may modify the proportion of events that are expressed and hence, the slope of the linear dependence. Using Chinese hamster cells in culture and the endpoint resistance to 6-thioguanine, mutations at high and at low dose rates by X- and Gamma-rays will be compared to determine if repair processes are evident in the low dose region. In the longer term, the work will be broadened to include other phenotypic markers, to human cells, and to other physical as well as to chemical inducers.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA033701-05
Application #
3171488
Study Section
Radiation Study Section (RAD)
Project Start
1983-02-01
Project End
1988-09-30
Budget Start
1987-02-01
Budget End
1988-09-30
Support Year
5
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Type
Schools of Veterinary Medicine
DUNS #
112617480
City
Fort Collins
State
CO
Country
United States
Zip Code
80523