Thames H D, Ruifrok A C, Mason K A
Department of Biomathematics, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Radiat Res. 1997 Feb;147(2):172-8.
The rate of cell production in hierarchical tissues is affected by the differentiation probability after each clonogen division and the frequency with which divisions take place. We have modified the latter by a high-fiber diet, which caused an increase in the BrdUrd labeling index (LI) in jejunal crypts of mice, and have tested for a change in tolerance using the in vivo colony assay. Clonogens were counted using the in vivo colony assay of crypt regeneration with Poisson correction. The LI was estimated by counting BrdUrd-labeled cells in longitudinal sections of complete crypts. Arrest in mitosis induced by injection of paclitaxel was used to test for a difference in the rate of crypt cell production in mice fed low- and high-fiber diets. Split-dose studies were used to test whether the change in proliferative status of the crypts was accompanied by changes in either the number of clonogens per crypt or their radiosensitivity, or an increased proliferative response to radiation-induced cell killing. We found an increase in the crypt LI induced by the high-fiber diet was 15-25% and was dependent on the time of day. The data on arrest in mitosis did not demonstrate a difference in cell production rates based on diet, possibly because of insufficient resolution of the assay. We conclude that the high-fiber diet had no effect on radiosensitivity, the number of clonogens per crypt (again, within the resolution of the assay) or the "repopulated dose," the dose represented by the shift in the dose-response curve for 2.5 days relative to that for 6 h. When the number of clonogens at the start of rapid proliferation was different (on account of different first doses), the repopulated dose was the same when 5 Gy X rays was given first but was higher for the animals on the high-fiber diet when 12 Gy was given first. The high-fiber diet caused an increase in the LI in the crypts that was not accompanied by any change in radiosensitivity or, within the resolution of the assay, numbers of clonogens per crypt. The increased LI also did not result in an increase in clonogen repopulation between split (and equal) doses. However, in split-dose experiments where the first dose was higher and as a consequence the number of clonogens at the start of the proliferative response was lower, there was evidence of a higher rate of clonogen production with the high-fiber diet than with the low-fiber diet.
在分层组织中，细胞产生的速率受每个克隆原细胞分裂后的分化概率以及分裂发生频率的影响。我们通过高纤维饮食改变了后者，这导致小鼠空肠隐窝中BrdUrd标记指数（LI）增加，并使用体内集落测定法测试耐受性的变化。使用隐窝再生的体内集落测定法并进行泊松校正来计数克隆原细胞。通过计数完整隐窝纵切片中BrdUrd标记的细胞来估计LI。注射紫杉醇诱导的有丝分裂停滞用于测试喂食低纤维和高纤维饮食的小鼠隐窝细胞产生速率的差异。采用分次剂量研究来测试隐窝增殖状态的变化是否伴随着每个隐窝中克隆原细胞数量、其放射敏感性的变化，或者对辐射诱导的细胞杀伤的增殖反应增加。我们发现高纤维饮食诱导的隐窝LI增加了15% - 25%，并且依赖于一天中的时间。有丝分裂停滞的数据未显示基于饮食的细胞产生速率存在差异，可能是因为该测定法的分辨率不足。我们得出结论，高纤维饮食对放射敏感性、每个隐窝中克隆原细胞的数量（同样，在测定法的分辨率范围内）或“再增殖剂量”没有影响，“再增殖剂量”是指相对于6小时的剂量 - 反应曲线，2.5天的剂量 - 反应曲线的偏移所代表的剂量。当快速增殖开始时克隆原细胞的数量不同（由于初始剂量不同），当先给予5 Gy X射线时，再增殖剂量相同，但当先给予12 Gy时，高纤维饮食组动物的再增殖剂量更高。高纤维饮食导致隐窝中LI增加，但在放射敏感性方面没有任何变化，或者在测定法的分辨率范围内，每个隐窝中克隆原细胞的数量没有变化。LI增加也未导致分次（且相等）剂量之间克隆原细胞再增殖增加。然而，在分次剂量实验中，当首次剂量较高且因此增殖反应开始时克隆原细胞的数量较低时，有证据表明高纤维饮食组的克隆原细胞产生速率高于低纤维饮食组。
