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Increase in hepatocyte and nuclear volume and decrease in the population of binucleated cells in preneoplastic foci of rat liver: A stereological study using the nucleator method
Author(s) -
Jack Elspeth M.,
Bentley Philip,
Bieri Francoise,
MuakkassahKelly Samar F.,
Stäubli Willy,
Suter Joseph,
Waechter Felix,
CruzOrive Luis M.
Publication year - 1990
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840110220
Subject(s) - binucleated cells , mitosis , ploidy , biology , pathology , population , hepatocyte , stereology , cell , cell nucleus , andrology , microbiology and biotechnology , cytoplasm , toxicity , medicine , endocrinology , genetics , in vitro , micronucleus , environmental health , micronucleus test , gene
Gamma‐glutamyltranspeptidase‐positive hepatocyte foci were produced in female rats given a single dose of diethylnitrosamine neonatally after birth and, after weaning, a diet containing phenobarbitone for 30 wk. The nucleator method, a new stereological approach, provided an efficient, unbiased estimate of mean cell volume in focal lesions and extrafocal areas. It also provided an unbiased sample of cells to estimate hepatocyte nuclear volume and the percentage of binucleated cells. The results showed an increase in the mean volume of mononucleated cells–from 4,700 μm〈3〉 in extrafocal areas to 12,700 μm〈3〉 in foci–and of binucleated cells–from 6,900 μm〈3〉 to 25,000 μm〈3〉. This demonstrated the hypertrophic effect of the carcinogenic treatment in focal lesions. A striking reduction in the proportion of binucleated cells was also observed in the preneoplastic lesions. Nuclear volume measurements from mononucleated and binucleated hepatocytes were used to assess ploidy. An apparent increase in nuclear ploidy, with no change in cellular ploidy, was noted in focal tissue when compared with nonfocal tissue. This appeared to be caused by an increase in mononucleated tetraploid cells and a reduction in binucleated cells with two diploid nuclei, indicating an altered mitotic mechanism in focal lesions. The significance of these changes in cell volume, apparent ploidy levels and binuclearity in preneoplastic foci is discussed in relation to the hepatocarcinogenic process.