PLOIDY AND NUCLEARITY OF RAT HEPATOCYTES AFTER COMPENSATORY REGENERATION OR MITOGEN-INDUCED LIVER GROWTH

PLOIDY AND NUCLEARITY OF RAT HEPATOCYTES AFTER COMPENSATORY REGENERATION OR MITOGEN-INDUCED LIVER GROWTH
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DOI:
10.1093/carcin/14.9.1825
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发表时间:
1993-09-01
期刊:
影响因子:
4.7
通讯作者:
COLUMBANO, A
COLUMBANO, A
中科院分区:
医学2区
文献类型:
--
作者:
MELCHIORRI, C;CHIECO, P;COLUMBANO, A

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在 Wistar 大鼠中,通过手术部分肝切除术(代偿性再生)或原发性有丝分裂原(直接增生)诱导细胞增殖,研究了不同倍性类别的大鼠肝实质细胞的分布模式。在增殖刺激后1、2、3、4和15天处死动物,并使用计算机辅助成像系统测量通过胶原酶灌注分离的肝细胞中的倍性和核度。对部分肝切除后进行再生的动物的肝细胞的分析显示,四倍体和八倍体单核细胞大量增加。最显着的特征是部分肝切除术后 3 天双核细胞几乎完全消失(从 20% 降至 < 1%)。相反,当用促细胞分裂剂硝酸铅处理后对肝细胞进行分析时,观察到大量双核细胞(40%)。治疗后 3 天时的最大增加主要发生在 4x2c 和 8x2c 区室中。这导致双核/单核细胞比率以及 (8c + 16c) : (2c + 4c) 比率总体增加。治疗后2周,硝酸铅引起的细胞学变化不可逆。由于在此期间细胞凋亡大量消除了过量的肝细胞,因此多倍体细胞似乎没有被优先消除。回归阶段结束时肝脏 DNA 含量与对照值相似。然而,由于倍性状态较高,治疗后 2 周肝脏中存在的细胞数量似乎低于对照组(约 16%)。当用另一种有丝分裂原(过氧化物酶体增殖剂萘非诺平)单一处理诱导肝脏生长时,观察到肝脏倍性状态略有增加;由于向更高倍性类别的转变(8c),在用奈非诺平单次治疗后3天观察到的DNA含量增加(+21%)似乎几乎完全由多倍性而不是由增生事件证明。
The distribution pattern of rat liver parenchymal cells of different ploidy classes was investigated in Wistar rats following cell proliferation induced by surgical partial hepatectomy (compensatory regeneration) or primary mitogens (direct hyperplasia). Animals were killed at 1, 2, 3, 4 and 15 days after the proliferative stimulus, and ploidy and nuclearity were measured using a computer-assisted imaging system in hepatocytes isolated by collagenase perfusion. Analysis of hepatocytes from animals undergoing regeneration after partial hepatectomy revealed a large increase in tetraploid and octoploid mononucleate cells. The most striking feature was the almost complete disappearance of binucleate cells (from 20% to < 1%) at 3 days after partial hepatectomy. On the contrary, when hepatocytes were analyzed after treatment with the mitogen lead nitrate, a high number of binucleate cells (40%) was observed. The increase that was maximal at 3 days after treatment occurred mainly in 4x2c and in 8x2c compartments. This resulted in an overall increase in the ratio of binucleate/mononucleate cells as well as in the ratio (8c + 16c) : (2c + 4c). The cytological changes induced by lead nitrate were not reversible 2 weeks after treatment. Because a massive elimination of excess liver cells occurred by apoptosis during this time period, it appears that polyploid cells are not preferentially eliminated. The hepatic content of DNA at the end of the regression phase was similar to control values. However, because of the higher ploidy state, the number of cells present in the liver 2 weeks after treatment appears to be lower than that of controls (approximately - 16%). When liver growth was induced by a single treatment with another mitogen, the peroxisome proliferator nafenopin, a slight increase in the ploidy state of the liver was observed; because of the shift towards higher ploidy classes (8c), the increase in DNA content observed 3 days after a single treatment with nafenopin (+ 21%) appears to be almost entirely justified by polyploidy rather than by a hyperplastic event.