Ijiri K, Potten C S
Br J Cancer. 1987 Feb;55(2):113-23. doi: 10.1038/bjc.1987.25.
Adult male mice were treated with one or two different doses of each of 18 different cytotoxic agents. They were sampled at various times (3-12h) thereafter, and the spatial distributions of cell death in the small intestinal crypts were studied. Dead or dying cells or cells carrying dead cell fragments were examined histologically, and all of these were recorded (for convenience as apoptotic fragments), relative to the cell position in the crypt. Thus, distributions of apoptotic fragments against cell position were determined. A regression analysis of the data obtained at different times after administration of each agent was undertaken and the position of the median of the spatial distribution of presumptive target cells was deduced for each cytotoxic agent. The accuracy of this median value was determined to be +/- 0.5 cell positions. From these median values, the different cytotoxic agents could be divided roughly into three groups: [3H]thymidine, isopropyl-methane-sulphonate, gamma-rays, bleomycin and adriamycin all have their median values (susceptible cells) at cell positions 4 to 6; bischlorethylnitrosourea, actinomycin D, cyclophosphamide and cycloheximide at cell positions 6-8; mechlorethamine, triethylenethiophosphoramide, vincristine, 5-fluorouracil, hydroxyurea and methotrexate at cell positions 8-11. The position of these medians was considered in relation to the killing of clonogenic cells. Preliminary studies on the distributions of dead cells after myleran, cis-platinum and heat (hyperthermia) were also reported. There is a general tendency for antibiotics and radiation to attack the lower cell positions in the crypt. Alkylating agents on the other hand have a somewhat broad spectrum of action. Antimetabolites and a microtubule dissociating agent act on higher cell positions. No difference could be detected between two different forms (sources) of actinomycin D. The changes in the yields of apoptotic and mitotic cells with time and the migration velocities of cells in the crypts carrying apoptotic fragments after exposure to cytotoxics are also presented.
成年雄性小鼠接受了18种不同细胞毒性药物中每种药物的一种或两种不同剂量的处理。此后在不同时间点（3 - 12小时）对它们进行取样，并研究小肠隐窝中细胞死亡的空间分布。对死亡或濒死细胞或携带死亡细胞碎片的细胞进行组织学检查，并将所有这些细胞（为方便起见作为凋亡碎片）相对于隐窝中的细胞位置进行记录。由此确定凋亡碎片相对于细胞位置的分布。对每种药物给药后不同时间获得的数据进行回归分析，并推断出每种细胞毒性药物推定靶细胞空间分布中位数的位置。确定该中位数的准确性为±0.5个细胞位置。根据这些中位数，不同的细胞毒性药物大致可分为三组：[3H]胸苷、异丙基甲磺酸盐、γ射线、博来霉素和阿霉素的中位数（敏感细胞）均在细胞位置4至6处；双氯乙基亚硝脲、放线菌素D、环磷酰胺和环己酰亚胺在细胞位置6 - 8处；氮芥、三乙撑硫代磷酰胺、长春新碱、5 - 氟尿嘧啶、羟基脲和甲氨蝶呤在细胞位置8 - 11处。考虑了这些中位数的位置与克隆细胞杀伤的关系。还报告了关于白消安、顺铂和热（高温）处理后死亡细胞分布的初步研究。一般来说，抗生素和辐射倾向于攻击隐窝中较低位置的细胞。另一方面，烷化剂的作用谱较广。抗代谢物和一种微管解离剂作用于较高位置的细胞。未检测到两种不同形式（来源）的放线菌素D之间存在差异。还呈现了暴露于细胞毒性药物后凋亡和有丝分裂细胞产量随时间的变化以及携带凋亡碎片的隐窝中细胞的迁移速度。
