PNAS paper on inverse radiation dose effects

["Karam, Andrew" <Andrew_Karam@URMC.Rochester.edu>]

If this abstract was previously posted to Radsafe, please accept my
apologies.  I didn't see it in the archives.  It is from the May 9, 2000
Proceedings of the National Academy of Sciences.

Andy

Andrew_Karam@URMC.Rochester.edu
===============================
Inverse radiation dose-rate effects on somatic and germ-line mutations and
DNA damage rates 
Michael M. Vilenchik* and Alfred G. Knudson Jr., 
Contributed by Alfred G. Knudson, Jr., March 7, 2000 
The mutagenic effect of low linear energy transfer ionizing radiation is
reduced for a given dose as the dose rate (DR) is reduced to a low level, a
phenomenon known as the direct DR effect. Our reanalysis of published data
shows that for both somatic and germ-line mutations there is an opposite,
inverse DR effect, with reduction from low to very low DR, the overall
dependence of induced mutations being parabolically related to DR, with a
minimum in the range of 0.1 to 1.0 cGy/min (rule 1). This general pattern
can be attributed to an optimal induction of error-free DNA repair in a DR
region of minimal mutability (MMDR region). The diminished activation of
repair at very low DRs may reflect a low ratio of induced ("signal") to
spontaneous background DNA damage ("noise"). Because two common DNA lesions,
8-oxoguanine and thymine glycol, were already known to activate repair in
irradiated mammalian cells, we estimated how their rates of production are
altered upon radiation exposure in the MMDR region. For these and other
abundant lesions (abasic sites and single-strand breaks), the DNA damage
rate increment in the MMDR region is in the range of 10% to 100% (rule 2).
These estimates suggest a genetically programmed optimatization of response
to radiation in the MMDR region. 
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