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首页> 外文期刊>British Journal of Cancer >Further studies on the response of intestinal crypt cells of different hierarchical status to eighteen different cytotoxic agents
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Further studies on the response of intestinal crypt cells of different hierarchical status to eighteen different cytotoxic agents

机译：进一步研究不同等级的肠隐窝细胞对18种不同细胞毒剂的反应

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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.
机译：成年雄性小鼠用一种或两种不同剂量的18种不同细胞毒剂中的每一种进行治疗。此后在不同时间（3-12h）取样，研究小肠隐窝中细胞死亡的空间分布。组织学检查死亡或垂死细胞或携带死亡细胞片段的细胞，并相对于隐窝中的细胞位置记录所有这些（为方便起见，作为凋亡片段）。因此，确定了针对细胞位置的凋亡片段的分布。进行每种药物给药后不同时间获得的数据的回归分析，并推导出每种细胞毒性药物的推定靶细胞空间分布中值的位置。该中值的准确度确定为+/- 0.5个像元位置。根据这些中值，可以将不同的细胞毒剂大致分为三组：[3H]胸苷，异丙基甲磺酸盐，γ射线，博来霉素和阿霉素在细胞位置4至6均具有其中值（易感细胞） ;在细胞位置6-8的双氯乙基亚硝基脲，放线菌素D，环磷酰胺和环己酰亚胺;甲乙胺，三亚乙基硫代磷酰胺，长春新碱，5-氟尿嘧啶，羟基脲和氨甲蝶呤在细胞位置8-11。这些中位数的位置被认为与杀伤克隆细胞有关。还报道了对黑麦芽孢杆菌，顺铂和热（体温过高）后死亡细胞分布的初步研究。抗生素和放射线通常会攻击隐窝的较低细胞位置。另一方面，烷基化剂具有较广的作用范围。抗代谢物和微管解离剂作用于较高的细胞位置。在放线菌素D的两种不同形式（来源）之间未检测到差异。还显示了凋亡和有丝分裂细胞的产量随时间的变化以及暴露于细胞毒素后携带凋亡片段的隐窝中细胞的迁移速度。

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