Review: The link between low-LET dose-response relations and the
underlying kinetics of damage production/repair/misrepair
Abstract
Purpose. To review current opinion on the production and temporal
evolution of low-LET radiobiological damage.
Methods. Standard
cell survival models which model repair/misrepair kinetics in order to
quantify dose-response relations and dose-protraction effects are
reviewed and interrelated. Extensions of the models to endpoints other
than cell survival, to multiple or compound damage processing pathways,
and to stochastic intercellular damage fluctuations are surveyed.
Various molecular mechanisms are considered, including DSB restitution
and binary misrepair.
Conclusions. (1) Linking dose-response
curves to the underlying damage production/processing kinetics allows
mechanistic biological interpretations of observed curve parameters.
(2) Various damage processing pathways, with different kinetics,
occur. (3) Almost every current kinetic model, whether based on binary
misrepair or saturable repair, leads at low or intermediate doses to
the LQ (linear-quadratic) formalism, including the standard
(generalized Lea-Catcheside) dependence on dose protraction. (4)
Two-track (beta) lethal damage is largely due to dicentric chromosome
aberrations, but one-track (alpha) lethal damage is largely caused by
other mechanisms, such as point mutations in a vital gene, small
deletions, residual chromosome breaks, induced apoptosis, etc. (5) A
major payoff for fifty years of radiobiological modeling is identifying
molecular mechanisms which underly the broadly applicable LQ
formalism.
International Journal of Radiation Biology 72, 351-374, 1997.
R.K. SACHS\(dg, P. HAHNFELDT* and D.J. BRENNER\(dd
\(dgDept. Math., University of California, Berkeley, CA 94720. *Joint
Center for Radiotherapy, Harvard University, Boston, MA 02115.
\(ddCenter for Radiological Research, Columbia University, New York, NY
10032.
Kinetics