Bijwaard Harmen, Brugmans Marco J P, Schöllnberger Helmut
RIVM, Laboratory for Radiation Research, Bilthoven, The Netherlands.
Radiat Res. 2006 Jun;165(6):741-4. doi: 10.1667/RR3548.1.
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.
最近，在一个两阶段癌症模型中观察到的克隆扩增促进现象被归因于起始细胞的微小过量替代概率。针对被正常细胞包围的单个中间细胞，对所提出的过量替代机制进行了评估。本文使用相同的生物学参数进一步研究了该机制。如果在对所提出机制的定量分析中考虑中间细胞克隆的形成，结果表明：（1）对于随着暴露而出现的促进作用的初始强烈增加，需要一个大得多且不太可能的过量替代概率；（2）如之前所提出的，对于高暴露情况下促进作用的平稳状态，无法通过中间细胞的多个正常邻居在一个细胞周期内失活来解释。也许通过对原始参数进行重新缩放可以部分解决这些差异，但这需要进一步研究。
