Health Effects of Alpha Emitters (Mechanistic Basis)
A.L. Brooks (Washington State University Tri-Cities)
In a large number of cell and molecular systems it is well established that high-LET alpha particles induce a linear dose-response relationship. These relationships seem to be rather independent of radiation dose-rate and time. However, when cancer incidence is evaluated, there are some alpha-induced tumor types that increase as a non-linear function of radiation dose. Some of these have a well defined "threshold" below which there is no detectable increase in cancer. Understanding the mechanistic differences in low dose responses for high- and low-LET radiation may elucidate why the differences in the shapes of the in vitro and in vivo curves exist. There are marked changes in gene expression following deposition of single alpha particles, which are not observed for low doses of low-LET radiation. These responses, in which many more cells are biologically altered than are traversed by the alpha particle, are termed "bystander effects". On the other hand, cells exposed to low-LET radiation have been demonstrated to change the number and types of genes expressed as a function of radiation dose. These changes result in "adaptive responses" that seem to be protective. The potential differences in mechanisms of cellular and molecular responses as a function of LET and cancer data from internally deposited alpha emitting radioactive material will be reported and evaluated in light of recent mechanistic research. This research funded by grant #DE-FG03-99ER62787 from U.S. Department of Energy, Office of Biological and Environmental Research to Washington State University.