Detrimental and protective bystander effects: a model approach.
This work integrates two important cellular responses to low doses, detrimental bystander effects and apoptosis-mediated protective bystander effects, into a multistage model for chromosome aberrations and in vitro neoplastic transformation: the State-Vector Model. The new models were tested on representative data sets that show supralinear or U-shaped dose responses. The original model without the new low-dose features was also tested for consistency with LNT-shaped dose responses. Reductions of in vitro neoplastic transformation frequencies below the spontaneous level have been reported after exposure of cells to low doses of low-LET radiation. In the current study, this protective effect is explained with bystander-induced apoptosis. An important data set that shows a low-dose detrimental bystander effect for chromosome aberrations was successfully fitted by additional terms within the cell initiation stage. It was found that this approach is equivalent to bystander-induced clonal expansion of initiated cells. This study is an important step toward a comprehensive model that contains all essential biological mechanisms that can influence dose-response curves at low doses.
Schöllnberger
H
H
Department of Materials Engineering and Physics and Biophysics, University of Salzburg, Salzburg, Austria. helmut.schoellnberger@sbg.ac.at
Mitchel
R E J
RE
Redpath
J L
JL
Crawford-Brown
D J
DJ
Hofmann
W
W
D024201:Bystander Effect / Q000502:physiology* / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects*; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects*; D003198:Computer Simulation; D019610:Cytoprotection / Q000502:physiology* / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D008954:Models, Biological; D011829:Radiation Dosage