Growth in high serum concentrations leads to rapid deadaptation of cells previously adapted to growth in an extremely low concentration of serum.
Growth in high serum concentrations leads to rapid deadaptation of cells previously adapted to growth in an extremely low concentration of serum.
复制标题
在高血清浓度下生长会导致先前适应在极低浓度血清中生长的细胞快速去适应。
DOI：
10.1073/pnas.88.21.9422
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发表时间：
1991
影响因子：
11.1
通讯作者：
Rubin,H
中科院分区：
文献类型：
--
作者：
Yao,A;Huang,W;Rubin,H
NIH3T3细胞亚系适应在0.25%小牛血清(CS)低密度下频繁传代(每隔2~3天)增殖，在10%CS中频繁连续传代3周。适应0.25%CS的细胞在10%CS中的平均倍增时间为16.9小时，而一直保存在10%CS中的细胞倍增的平均时间为14.6小时，因此在较高的血清浓度下对后者的选择较弱。当适应细胞在10%CS中传代两次后，在0.25%CS中进行生长试验，在开始指数生长之前有4天的滞后期，饱和密度降低。随着细胞在10%CS中传代次数的增加，0.25%CS中的生长进一步延迟。在10%CS的群体中，0.25%的群体在几天后显著延迟生长，这与从适应群体中选择稀有的非适应突变体的10%CS和这种变化的表观起源是不一致的。在0.25%CS中混合使用适应细胞和非适应细胞的重建实验支持了这一解释。适应群体中有8个无性系在0.25%CS中单代后表现出一定的生长能力丧失，但不同无性系的丧失程度不同。结果支持这样的观点，即适应种群中的所有细胞在高度受限的条件下，随着生长限制的解除而失去其生长潜力。它们与渐进状态选择的概念是一致的，在渐进状态选择中，选择对单个细胞波动的代谢状态进行操作，而不是对遗传变异进行选择。
A subline of NIH 3T3 cells adapted to multiply in 0.25% calf serum (CS) by frequent passage (every 2-3 days) at low population density in 0.25% CS was deadapted by frequent successive passages of the cells in 10% CS for 3 weeks. The cells adapted to 0.25% CS multiplied with an average doubling time of 16.9 hr in 10% CS, and cells that had always been kept in 10% CS multiplied with an average doubling time of 14.6 hr, so there was weak selection for the latter in the higher serum concentration. When adapted cells were subjected to two passagers in 10% CS prior to assay of growth in 0.25% CS, a 4-day lag period was evident before commencement of exponential growth, and there was a decrease in saturation density. Further delay of growth in 0.25% CS developed as the number of passages of cells in 10% CS increased. The marked delay of growth in 0.25% CS of the bulk population after a few days in 10% CS argued against selection in 10% CS of rare nonadapted mutants from the adapted population and for an epigenetic origin of the change. Reconstruction experiments utilizing adapted cells mixed with non-adapted cells in 0.25% CS buttressed this explanation. Eight clones of the adapted population exhibited some loss of growth capacity in 0.25% CS after a single passage in 10% CS, though the extent of loss varied from clone to clone. The results support the idea that all cells in the adapted population respond to the lifting of growth constraints with loss of their growth potential under highly constrained conditions. They are consistent with the concept of progressive state selection in which selection operates on fluctuating metabolic states of individual cells rather than on genetic variants.