CONTROLLED DEATH (APOPTOSIS) OF NORMAL AND PUTATIVE PRENEOPLASTIC CELLS IN RAT-LIVER FOLLOWING WITHDRAWAL OF TUMOR PROMOTERS
CONTROLLED DEATH (APOPTOSIS) OF NORMAL AND PUTATIVE PRENEOPLASTIC CELLS IN RAT-LIVER FOLLOWING WITHDRAWAL OF TUMOR PROMOTERS
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DOI：
10.1093/carcin/5.4.453
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发表时间：
1984-01-01
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;LAUER, B;SCHULTEHERMANN, R
在正常肝脏和肝局灶中研究了停止诱导/启动子治疗后增生的消退情况。给大鼠注射高剂量的醋酸环丙孕酮（CPA），一种合成的性类固醇，使大鼠的肝脏大小增加了一倍；停药后肝脏大小下降，总肝脏DNA在6天内消失27%。从渐开线肝到坏死的组织学切片，可见大量凋亡小体（AB）；这些发现表明，停止CPA治疗后过量肝脏DNA的消除是由于细胞凋亡控制的细胞死亡。在进一步的一系列实验中，假定的肿瘤前灶是由单剂量的n -亚硝基somorpholine产生的，随后通过10或28周的苯巴比妥（PB）治疗刺激生长。停用PB后，正常肝脏及病灶内可见大量AB；在这两种情况下，再用PB治疗可减少AB的出现。似乎PB抑制细胞死亡可能有助于肿瘤的促进。在所有测试条件下，灶内发现的AB比肝脏非灶部位发现的AB多，表明灶内细胞更新增强。病灶对控制细胞死亡机制的明显敏感性可能最终为消除肿瘤前病变提供了一种手段。
The regression of hyperplasia after cessation of inducer/promoter treatment was studied in normal liver and in liver foci. High doses of cyproterone acetate (CPA), a synthetic sex steroid, were administered to rats and produced a doubling of liver size; after cessation of treatment liver size declined, and 27% of the total liver DNA disappeared within 6 days. In histological sections from the involuting liver to necroses, but numerous apoptotic bodies (AB) were found; treatment with CPA interrupted the formation of AB. These findings suggest that elimination of excess liver DNA after cessation of CPA treatment is due to controlled cell death by apoptosis. In a further series of experiments putative preneoplastic foci were produced by a single dose of N-nitrosomorpholine and subsequently stimulated to grow by 10 or 28 wk of phenobarbital (PB) treatment. After withdrawal of PB numerous AB were present in normal liver and in the foci; in both, retreatment with PB decreased the appearance of AB. It appears that inhibition of cell death by PB may contribute to tumor promotion. Under all conditions tested more AB were found in the foci than in non-focal parts of the liver, suggesting an enhanced cell turnover in foci. The apparent sensitivity of foci to mechanisms controlling cell death might eventually provide a means for elimination of preneoplastic lesions.