Ploidy and nuclearity of rat hepatocytes after compensatory regeneration or mitogen-induced liver growth

Abstract

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 4 x 2c and in 8 x 2c 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.