title: The link between low-LET dose-response relations and the underlying kinetics of damage production/repair/misrepair.
abstract: OBJECTIVE
  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 double strand breaks 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 50 years of radiobiological modelling is identifying molecular mechanisms which underly the broadly applicable LQ formalism.
authors.affiliation: Department of Mathematics, University of California, Berkeley 94720, USA.
authors.forename: R K
authors.initials: RK
authors.lastname: Sachs
authors.forename: P
authors.initials: P
authors.lastname: Hahnfeld
authors.forename: D J
authors.initials: DJ
authors.lastname: Brenner
mesh_terms: D000818:Animals; D004247:DNA / Q000378:metabolism* / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007700:Kinetics; D018499:Linear Energy Transfer
chemical_list: D004247:DNA