“…Whatever might be the functional meaning of polyploidization (cf. references 46,47), it should be mentioned that ploidy shifts occur not only in hepatic differentiation and regeneration (35,36,48,49), but also, for example, following carbon tetrachloride poisoning (50) and in the course of experimental inflammatory processes (51) .…”
The changes occurring in rat hepatocytes during a 5 day period of treatment with phenobarbital were determined by morphometric and biochemical methods, particular attention being paid to the endoplasmic reticulum. The hepatocytic cytoplasm played an overwhelming part in the liver hypertrophy, while the hepatocytic nuclei contributed to only a moderate extent. The endoplasmic reticulum accounted for more than half of the increase in cytoplasmic volume. The increase in the volume and number of hepatocytic nuclei in the course of phenobarbital treatment was associated with changes in the ploidy pattern. Until the 2nd day of treatment both the rough-surfaced endoplasmic reticulum (RER) and the smooth-surfaced endoplasmic reticulum (SER) participated in the increase in volume and surface of the whole endoplasmic reticulum (ER). Subsequently, the values for RER fell again to control levels, whereas those for SER continued to increase, with the result that by the 5th day of treatment the SER constituted the dominant cytoplasmic element. The specific volume of mitochondria and microbodies (peroxisomes) remained constant throughout the duration of the experiment, while that of the dense bodies increased. The specific number of mitochondria and microbodies displayed a significant increase, associated with a decrease in their mean volume. The phenobarbital-induced increase in the phospholipid and cytochrome P-450 content of the microsomes, as well as in the activities of microsomal reduced nicotinamide-adenine dinucleotide phosphate-cytochrome c reductase and N-demethylase, was correlated with the morphometric data on the endoplasmic reticulum.
“…Whatever might be the functional meaning of polyploidization (cf. references 46,47), it should be mentioned that ploidy shifts occur not only in hepatic differentiation and regeneration (35,36,48,49), but also, for example, following carbon tetrachloride poisoning (50) and in the course of experimental inflammatory processes (51) .…”
The changes occurring in rat hepatocytes during a 5 day period of treatment with phenobarbital were determined by morphometric and biochemical methods, particular attention being paid to the endoplasmic reticulum. The hepatocytic cytoplasm played an overwhelming part in the liver hypertrophy, while the hepatocytic nuclei contributed to only a moderate extent. The endoplasmic reticulum accounted for more than half of the increase in cytoplasmic volume. The increase in the volume and number of hepatocytic nuclei in the course of phenobarbital treatment was associated with changes in the ploidy pattern. Until the 2nd day of treatment both the rough-surfaced endoplasmic reticulum (RER) and the smooth-surfaced endoplasmic reticulum (SER) participated in the increase in volume and surface of the whole endoplasmic reticulum (ER). Subsequently, the values for RER fell again to control levels, whereas those for SER continued to increase, with the result that by the 5th day of treatment the SER constituted the dominant cytoplasmic element. The specific volume of mitochondria and microbodies (peroxisomes) remained constant throughout the duration of the experiment, while that of the dense bodies increased. The specific number of mitochondria and microbodies displayed a significant increase, associated with a decrease in their mean volume. The phenobarbital-induced increase in the phospholipid and cytochrome P-450 content of the microsomes, as well as in the activities of microsomal reduced nicotinamide-adenine dinucleotide phosphate-cytochrome c reductase and N-demethylase, was correlated with the morphometric data on the endoplasmic reticulum.
“…If all hepatocytes undergo S phase and cell division after PHx, the ploidy should remain constant. However, it has long been known that hepatocyte ploidy is increased after PHx [14,36,37], suggesting that hepatocytes do not undergo conventional cell division. Previously, no convincing methods were available to investigate cell division in hepatocytes; however, we recently developed a genetic tracing method to directly assess cell division using hydrodynamic tail vein injection (HTVi) for effective delivery of plasmids into hepatocytes [38-40].…”
Section: Introductionmentioning
confidence: 99%
“…While it has long been known that ploidy of hepatocytes increases after PHx [14,36,37,62], its mechanism remains unknown. Although a majority of hepatocytes undergo S phase in regenerating liver after 70% PHx, not all hepatocytes undergo cell division, resulting in an increase in ploidy.…”
The liver has a remarkable capacity to regenerate. Even with surgical removal (partial hepatectomy) of 70% of liver mass, the remnant tissue grows to recover the original mass and functions. Liver regeneration after partial hepatectomy has been studied extensively since the 19th century, establishing the long-standing model that hepatocytes, which account for most of the liver weight, proliferate to recover the original mass of the liver. The basis of this model is the fact that almost all hepatocytes undergo S phase, as shown by the incorporation of radioactive nucleotides during liver regeneration. However, DNA replication does not necessarily indicate the execution of cell division, and a possible change in hepatocyte size is not considered in the model. In addition, as 15–30% of hepatocytes in adult liver are binuclear, the difference in nuclear number may affect the mode of cell division during regeneration. Thus, the traditional model seems to be oversimplified. Recently, we developed new techniques to investigate the process of liver regeneration, and revealed interesting features of hepatocytes. In this review, we first provide a historical overview of how the widely accepted model of liver regeneration was established and then discuss some overlooked observations together with our recent findings. Finally, we describe the revised model and perspectives on liver regeneration research.
“…It has been reported from studies on liver regeneration, that with the onset of the wave of cell divisions, the number of binuclear cells falls with a con comitant shift to higher ploidy classes, as being attributable to the fusion of the nuclei of binucleated cells [Bucher, 1963;Watanabe, 1970;James, 1977]. Direct cytological evidence of mitotic fusion in binuclear cells has been brought forward by James [1977], This shift in cell populations is also influenced by hormones [Geschwind et al;1958;Carriere, 1969], and environmen tal factors [Heizer, 1955].…”
The distribution pattern of rat liver parenchymal cells of different ploidy classes has been investigated with isolated liver cell preparations on four different time points of the day. The percentage distribution of different ploidy populations was found to fluctuate along the activity-rest cycle of the animals. The mononuclear tetraploid (MT) cell population showed the strongest time-dependent distribution pattern with a 10% variation around the 24 h mean, the variations in the binuclear diploid (BD) cells being somewhat less obvious, but clearly present. The mononuclear diploid cells and the binuclear tetraploid cells occurred in a virtually constant percentage. An inverse correlationship was noted between MT and BD cells, the increase in the number of MT cells being accompanied by a decrease in the number of BD cells. This interdependency in the presence of the two cell types can be related to their relationship in the process of formation.
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