Response of intestinal cells of differing topographical and hierarchical status to ten cytotoxic drugs and five sources of radiation.
Response of intestinal cells of differing topographical and hierarchical status to ten cytotoxic drugs and five sources of radiation.
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DOI：
10.1038/bjc.1983.25
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发表时间：
1983-02
影响因子：
8.8
通讯作者：
Potten, C S
中科院分区：
文献类型：
--
作者：
Ijiri, K;Potten, C S
记录了在不同剂量的10种不同药物以及内、外照射(氚、伽马射线、X射线和中子的β粒子)照射后不同时间，成年哺乳动物小肠粘膜上皮细胞的细胞死亡的空间分布。细胞死亡，表现为固缩或凋亡，在小肠隐窝一侧的每个细胞位置都有记录。以死细胞在每个细胞位置的分布形式的结果表明，每种不同的细胞毒剂倾向于优先作用于特征小范围的细胞位置。由于细胞位置可能与家系树或细胞谱系中的层级细胞位置有关，因此每个药物往往对谱系中特定位置的细胞起最大的作用。阿霉素和各种形式的辐射倾向于优先杀死细胞位置4-5的细胞，即在谱系非常早期的细胞上，可能是干细胞。异丙基甲烷磺酸盐、氮芥末和可能的放线菌素D作用于细胞位置6-7，而5-氟尿嘧啶、马利兰、环磷酰胺和放线菌亚胺倾向于杀死细胞位置7-9的细胞。长春新碱和羟基脲是对隐窝最上层的细胞表现出特异性的两种药物，即作用于细胞位置10或11的细胞谱系的最新转移群体。数据还表明，尽管细胞大量死亡和细胞产量减少，正常的健康细胞仍继续沿着隐窝向上迁移到绒毛上。
The spacial distribution of cell death among the epithelial cells lining the adult mammalian small intestinal mucosa at various times after a range of doses of 10 different drugs as well as after internal or external irradiation (beta particles from tritium, gamma- and X-rays and neutrons) has been recorded. Cell death, expressed as pycnosis or apoptosis, has been recorded for each cell position up the side of the crypts of the small intestine. The results, in the form of distributions of dead cells at each cell position, show that each of the various cytotoxic agents tends to act preferentially over a characteristic small range of cell positions. Since cell position is likely to be related to hierarchical cell position within a family tree or cell lineage, each agent tends to act with greatest efficiency on cells at a particular position within the lineage. Adriamycin and the various forms of radiation tend to kill cells preferentially at cell position 4-5 i.e. on cells very early in the lineage, probably stem cells. Isopropyl-methane-sulphonate, nitrogen mustard and possibly Actinomycin-D act on cell position 6-7, while 5-fluorouracil, Myleran, cyclophosphamide, and cycloheximide tend to kill cells at cell position 7-9. Vincristine and hydroxyurea are the 2 agents that exhibit a specificity for cells highest up the crypt, i.e. latest in transit population of the cell lineage by acting on cell positions 10 or 11. The data also suggest that normal healthy cells continue to migrate up the crypt and onto the villus in spite of considerable cell death and reduced cell production.