Can promotion of initiated cells be explained by excess replacement of radiation-inactivated neighbor cells?
Recently, the observed promotion in the clonal expansion of a two-stage cancer model was attributed to a small excess replacement probability for the initiated cells. The proposed mechanism of excess replacement was evaluated for single intermediate cells surrounded by normal cells. This paper investigates this mechanism further using the same biological parameters. If the formation of clones of intermediate cells is taken into account in a quantitative analysis of the proposed mechanism, it turns out that (1) for the initial strong increase of the promotional effect with exposure, a much larger and unlikely excess replacement probability is needed, and (2) the leveling of the promotional effect for high exposures cannot be explained by multiple normal neighbors of an intermediate cell being inactivated within one cell cycle, as it had been suggested. Perhaps these discrepancies could be partly resolved by a re-scaling of the original parameters, but this should be investigated further.
Bijwaard
Harmen
H
RIVM, Laboratory for Radiation Research, Bilthoven, The Netherlands. Harmen.Bijwaard@rivm.nl
Brugmans
Marco J P
MJ
Schöllnberger
Helmut
H
D024201:Bystander Effect / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects*; D002471:Cell Transformation, Neoplastic / Q000473:pathology* / Q000528:radiation effects*; D003198:Computer Simulation; D004307:Dose-Response Relationship, Radiation; D008954:Models, Biological; D009369:Neoplasms / Q000473:pathology*; D009381:Neoplasms, Radiation-Induced / Q000473:pathology*; D011829:Radiation Dosage