[An androgenic program of expression of the particular estrogen-binding protein is present in male rats in all hepatocytes].

Radioligand and immunohistochemical analysis was used for studying the expression of an unusual estrogen-binding protein (UEBP) in the regenerated liver of male rats poisoned with CCl4. As a result of CCl4 poisoning, most hepatocytes intensely producing UEBP and located in the central part of the liver lobules are destroyed (40 to 90% of the liver parenchymal cells). Dead cells are substituted by new hepatocytes formed due to proliferation of periportal hepatocytes in which UEBP is expressed at a low level.

[The effect of the alkylating carcinogen dipin on the proliferation, the level of polyploidy development and on micronucleus formation in a population of parent and newly formed hepatocytes].

In the process of hepatocarcinogenesis induced by dipin and partial hepatectomy in mice, initial hepatocytes are gradually replaced with a population of newly formed hepatocytes which originate from oval cells (Radaeva, Factor, 1990). It has been shown that the increase in hepatocarcinogenesis duration (2-11 weeks) along with the intensification of oval-cell reaction are accompanied by a progressive injury of cell genome in the initial hepatocyte population. This injury manifests itself by an accumulation of cells with micronuclei as well as by the development of high levels of polyploidy and aneuploidy.

[The formation of oval-cell ducts during hepatic carcinogenesis in mice. Its relationship to the pre-existing canals of Hering].

It has been shown that a population of the oval cells is formed in mouse liver during the dipin-induced carcinogenesis (Radaeva, Factor, 1990b). This paper deals with the origin of the oval cells and their proliferation potential depending on localization in the liver lobule. Series of semithin liver sections were studied under the light microscope and detected labeled cells analyzed under electron microscope on serial ultrathin sections.

[The growth of preneoplastic hepatocytes in the spleen of recipient mice].

Hepatocytes and the fraction of non parenchymal cells enriched with oval cells were extracted from the preneoplastic mouse liver at the stage of hyperplastic node formation and implanted into the spleen. In 14-16 months after the transplantation, multiple islets of hepatocytes which replaced up to 25% of the spleen cut area, were found in 57% (4 of 7) and 22% (8 of 36) of recipients respectively. The hepatocytes formed 2-3-cell bulks or solid masses organized into multicellular trabecules, and expressed biliary capillary antigen, albumin and transferrin.

[New differentiation markers of mouse liver epithelial cell lines].

We describe two new markers of mouse liver epithelial cells detected by monoclonal antibodies. Immunomorphological localization of antigens was performed using light and electron microscopy. Antigen G7 is a marker of cholangiocytes and oval cells.

[The stem-cell reserve of the liver].

This paper considers the problem of epithelial stem cells of the liver and possibilities of its experimental solution. Authors' own data obtained with the model of induced hepatocarcinogenesis in mice are discussed; the experiments were performed using electron microscopy, autoradiography and immunochemistry. In accordance with these data, Gering cells are stem cells of the liver, and oval cells correspond to committed precursors capable to differentiation in either hepatocellular or cholangiolar direction under the conditions of periportal microenvironment.

[The cellular localization of the unusual estrogen-binding protein in the liver of rats under different hormonal states].

The localization of an unusual estrogen-binding protein (UEBP) was studied in the rat liver using indirect immunoperoxidase reaction in intact rats and after different hormonal influences. The distribution of the UEBR in normal males displays a form of a gradient with the maximum near the central veins. The gradient is absent in normal females.

[Common antigens of oval cells and cholangiocytes in the mouse. Their detection by using monoclonal antibodies].

Monoclonal antibodies (MAb) were produced against antigens (Ag) of oval cells isolated from the preneoplastic murine liver. To suppress the immune response to major antigens common with hepatocytes, the principle of anti-idiotype immunization was employed. Characteristics of three MAb reacting selectively with the foci of oval cell proliferation are described.

[Dynamics of the development of oval cell population induced in the liver by dipin and partial hepatectomy].

It has been shown that dipin in combination with partial hepatectomy (model of dipin hepato-carcinogenesis) induces massive oval cell proliferation. The main stages of oval cells development examined by means of light microscopy of half-thin slices are the following: 1) appearance around portal tracts--1-3 weeks; 2) migration into parenchyma along terminal branches of portal vessels--3-8 weeks; 3) maximum development--8-10 weeks; 4) induction focuses of growth of new formed hepatocytes around portal tracts--8-10 weeks; 5) forcing of oval cells towards the centre of liver lobules and their elimination. There was close correlation between oval cells development, fibrosis and inflammation.

[The differentiation of oval cells into hepatocytes during induced hepatic carcinogenesis in mice. An electron microscopic study].

An electron microscopic study of murine oval cells, induced by a single injection of genotoxic agent dipin and by a partial hepatectomy, has shown that their ultrastructure and direction of differentiation depend on localization in the liver lobule. Oval cells around portal tracts go through three stages of development: low differentiated cells 4.40 +/- 0.

[The enzymatic isolation of hepatocytes from the mouse liver].

A modified version of the two-step enzymatic method for isolation of hepatocytes from the liver of adult mice is described. The method yields 6.10(7)-7.

[Complete change of the cell composition of the liver parenchyma following exposure to dipin and partial resection].

The phenomenon of total replacement of preexisting and damaged hepatocytes in mice were demonstrated by the method of autoradiography. Adult mice were injected an alkylating drug Dipin 2 h prior to partial hepatectomy and then proliferating cells were labelled by means of multiple injections of 14C-thymidine. Dipin in combination with mitotic stimulation induced multiple mitotic aberrations in proliferating hepatocytes resulting in degeneration, death and then elimination of prelabelled liver cells.

[Spontaneous hepatomas in hybrid mice (CBA x C57Bl/6)F1].

The spontaneous hepatomas of male mice (CBA X C57B1/6)F1 were studied using complex cytologic, histologic, immunochemical, and cytochemical methods. The AFP was detected in trace amount in the serum of tumour-bearing mice and in single cells of hepatomas. As a rule the hepatocarcinoma cells have the polymodal DNA distribution (2C-8C) with major peak of 4 C (in 18 out of 26 cases).

[Ploidy level and alpha-fetoprotein production in spontaneous murine hematomas in relation to the degree of histological differentiation].

Comparative morphological, cytospectrophotometric and immunochemical studies were carried out on 26 hepatocarcinomas of various malignancy excised from 21 F1 (CBA X C57B16) mice. It has been shown that in morphologically similar hepatomas the ploidy level and alpha-fetoprotein production intensity may vary markedly. Highly differentiated carcinomas usually of smaller sizes and homogeneous morphology have the modal class nuclei with tetraploid (6 cases) or octaploid (3 cases) DNA content.

[Analysis of the DNA content of urethane-induced liver tumors in mice].

Administration of urethan (three times per 1 mg calculated per 1 g of the animal mass) after partial hepatectomy resulted in the development of liver tumours classified as adenomas in 62.8 per cent of mice 12 months after treatment. In the cells isolated from 85 adenomas and from the surrounding liver, DNA-fuchsin content was determined cytophotometrically.

[Urethane inhibition of DNA synthesis in the hepatocytes of the regenerating liver in mice].

Hepatocarcinogen urethane (ethyl carbamate) inhibits DNA synthesis in the regenerating mice liver when administered at the peak of stimulated proliferation--46 hours after partial hepatectomy. The inhibition is temporary and reversible. The maximum inhibition of 3H-thymidine incorporation in the cells is observed 12 hours after urethane administration, and the effect is removed following 20 hours after administration.

[DNA content in cells of spontaneous hepatomas in CBA mice].

The DNA content was measured in the cells of 37 well-differentiated spontaneous hepatomas from 20 CBA mice aged 18 to 22 months. In all the cases, the DNA distribution pattern was polymodal, with the class of tetraploid cells being predominant. It was independent of the tumor ability to produce AFP.

An anticancer drug prospidine: failure to reveal antimitotic and clastogenic action on regenerating mouse liver.

Prospidine is an anticancer drug used in oncological practice in the USSR. It is characterized by only a slight toxicity and the absence of such side-effect as the hemopoiesis suppression. The mechanism of tumor growth inhibition by prospidine is still open to question.

[Formation of aberrant polyploid hepatocytes in exposure to the alkylating preparation dipin and to stimulation of proliferation].

One month after the treatment of mice with the alkylating drug Dipin followed by partial hepatectomy 4.7--35.1% of hepatocytes with micronuclei and nuclear bridges in liver were registered.

[Changes in the nature of the hepatocyte proliferation in the liver and adenomatous nodes of mice in CC14-induced carcinogenesis].

A study was made of cell proliferation and DNA content in the liver of SWR mice after 1, 7, 41 and 52 administrations of CCl4 made at 3-4 daily intervals. After 41 and 52 administrations of CCl4 the liver of all the animals demonstrated multiple small nodules and single large nodes. Cell proliferation in liver and large nodes was analyzed by cytophotometry and radioautography with the use of double isotopic label.

[Polyploidization of mouse hepatocytes following repeated exposure to carbon tetrachloride].

A study was made of a change in the cell composition of the liver during regeneration induced by repeated (up to 8 times) administration of carbon tetrachloride with a one-month interval. The second administration entailed total polyploidization of hepatocytes. The subsequent stimulation of the regeneration process greatly enhanced polyploidization, with octoploid hepatocytes becoming the predominant cell type.

Kinetics of cellular proliferation in regenerating mouse liver pretreated with the alkylating drug dipin.

The effect of prior exposure to the alkylating drug 1,4-Bis[N,N'-di(ethylene)-phosphamide] piperazine (Dipin) on the cell cycle progression in a regenerating mouse liver is reported, using cytological, autoradiographical and DNA-cytophotometrical methods. In Dipin-treated animals 3H-TdR pulse labelled nuclei appeared 22 h after the partial hepatectomy, followed by a rapid rise in labelling index to a very high level between 43-54 h, and then by a gradual decline to 72 h. Four injections of 3H-thymidine at 16 h intervals resulted in 89% labelling of hepatocytes at 72 h.

[Effect of the alkylating agent, dipin, on induced hepatocyte proliferation. II. An increase in the DNA synthesis period].

The alkylating drug dipin was injected to mice 2 hours before a partial hepatectomy. The duration of DNA synthesis of proliferating hepatocytes was determined by means of cytophotometry of DNA mass in the nuclei, labeled with 3H-thymidine 30 hours after the operation. The DNA mass was doubled simultaneously in diploid and tetraploid nuclei within 18-26 hours.

[Effect of the alkylating agent dipin on the induced proliferation of hepatocytes. I. The kinetics of the cell population].

The alkylating drug dipin was injected to mice 2 hours before a partial hepatectomy. Liver regeneration was characterized by a decrease of the intensity of 3H-thymidine label, an increase of the labeled cell index, absence of mitoses, constant number of binuclear cells. The analysis of these data has shown that dipin causes a sharp (more than by 2 times) increase of the S-period and prolonged (up to 6--20 days) blocking of cells in the G2-period.