DETERMINATION OF THE LENGTH OF THE HISTOLOGICAL STAGES OF APOPTOSIS IN NORMAL LIVER AND IN ALTERED HEPATIC FOCI OF RATS
DETERMINATION OF THE LENGTH OF THE HISTOLOGICAL STAGES OF APOPTOSIS IN NORMAL LIVER AND IN ALTERED HEPATIC FOCI OF RATS
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DOI：
10.1093/carcin/11.5.847
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发表时间：
1990-05-01
期刊：
影响因子：
4.7
通讯作者：
SCHULTEHERMANN, R
中科院分区：
文献类型：
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作者：
BURSCH, W;PAFFE, S;SCHULTEHERMANN, R
细胞凋亡是细胞死亡的一种形式，参与各种器官和肿瘤中细胞数量的调节。在组织切片中通过凋亡的细胞损失的定量测定除了凋亡细胞的计数之外，还需要关于凋亡的组织学可见阶段的持续时间的信息。在这里，我们描述了一种方法，以确定在（i）正常和（ii）推定的癌前组织的肝脏细胞凋亡的持续时间。(i)用高剂量的肝促分裂原醋酸环丙孕酮（CPA）处理雌性大鼠以诱导肝脏增生。停止CPA治疗后，增生部分消退，过多的肝细胞通过凋亡消除。给予CPA以阻断细胞凋亡的起始，此后研究了从肝脏中消除凋亡细胞残留物（凋亡小体，AB）的时间过程。发现细胞凋亡的组织学阶段的平均持续时间为0.4。3小时(ii)单剂量N-亚硝基吗啉和随后的促进39周的苯巴比妥（PB）在大鼠肝脏中产生表型改变的细胞灶。PB被撤回以停止灶生长并刺激凋亡。然后用PB再次治疗大鼠以阻止病灶中细胞凋亡的启动。结果表明，大多数凋亡小体在PB后4 h内消失，表明在病灶中的凋亡阶段与正常肝脏一样短。最后给出了计算细胞凋亡损失率的简单公式。所提出的方法可以为致癌作用数学模型的定量癌症风险评估提供数据。
Apoptosis is a form of cell death involved in the regulation of cell number in various organs and tumors. Quantitative determination of cell loss through apoptosis in histological sections requires, in addition to counts of apoptotic cells, information on the duration of the histologically visible stages of apoptosis. Here we describe a method to determine the duration of apoptosis in (i) normal and (ii) putative preneoplastic tissue of the liver. (i) Female rats were treated with high doses of the hepatomitogen cyproterone acetate (CPA) to induce liver hyperplasia. Aftr stopping CPA treatment, the hyperplasia partially regressed and excessive hepatocytes were eliminated by apoptosis. CPA was given to block the initiation of apoptosis, and thereafter the time course of elimination of apoptotic cell residues (apoptotic bodies, ABs) from the liver was studied. The mean duration of the histological stages of apoptosis was found to be .apprx. 3 h. (ii) Phenotypically altered cell foci in rat liver were produced by a single dose of N-nitrosomorpholine and subsequent promotion for 39 weeks with phenobarbital (PB). PB was withdrawn to stop foci growth and to stimulate apoptosis. Then rats were retreated with PB to block initiation of apoptosis in foci. The results indicate that the majority of apoptotic bodies in foci disappeared within 4 h after PB, suggesting that the stages of apoptosis are as short in foci as in normal liver. Finally a simple formula is given to calculate the cell loss rate by apoptosis. The method presented may provide data for quantitative cancer risk assessment from mathematical models of carcinogenesis.