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Biomedical subjects

I V Uryvaeva

Publications and source records attributed to I V Uryvaeva.

At least 19 recordsLinked to original sources
PubMed1995

An improved method of mouse liver micronucleus analysis: an application to age-related genetic alteration and polyploidy study.

The performance of a micronucleus test in liver cells in vivo requires two laborious procedures: stimulation of hepatocytes to division and dissociation of liver tissue into a single-cell suspension. We propose the method of inhalation treatment of mice with carbon tetrachloride to induce cell proliferation and alkaline dissociation of previously fixed tissue. The micronucleus incidence and ploidy classes in terms of cytophotometric DNA content were determined in liver of mice of three age groups (around 2.5, 5.0 and 7.0 months old) after CCl4 treatment or partial hepatectomy. The data obtained show that both methods give the same results. The fraction of micronucleated hepatocytes was 0.69% at the age of 2.5 months; it increased to 8.5% and then to 13.5% at 5.0 and 7.0 months respectively. Simultaneously, the ploidy classes changed both with the aging of the animal and after induced liver regeneration. The percentage distribution of micronucleated cells by ploidy class showed that cells carrying micronuclei were the higher ploidies rather than the population in general. Since polyploid cells contain multiple molecular targets for genetic damage, the micronucleation index per genome unit was estimated. Then the real rate of accumulation of both intrinsic endogenous (and probably the exogenously induced) preclastogenic genetic alterations in hepatocytes during the adulthood of mice was evaluated to be 0.03% per diploid genome per day. This seems to be the first description of the phenomenon of liver cell aging in terms of micronuclear aberrations.

Administration, Inhalation↗
PubMed1988

[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. New parenchymal tissue originated from non-labelled preneoplastic nodules. These hepatocyte nodules grew in size, propagated and 8-10 months later completely replaced the preexisting hepatocytes.

Alkylating Agents↗
PubMed1987

[Cytogenetic study of the effect of gossypol on mouse germ cells].

The clastogenic and mutagenic activities of a new antifertility and antitumor agent gossypol were studied in the mouse male germ cells. Results of the present work indicate that at the doses 125 and 250 mg/kg the drug does not significantly increase frequencies of the micronuclei in the early spermatids and sperm head abnormalities. Hence, genotoxic influence can not be proposed as responsible for the antifertility effect of gossypol.

Animals↗
PubMed1986

[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. Three types of DNA distribution were distinguished, with the mode in the region of near-diploid (26%), near-tetraploid (71.8%), or near-octaploid (2.2%) DNA value. Most commonly DNA distributions were polymodal, but unimodal ones also occurred. The number of binucleated cells in tumours was significantly decreased. In the liver of one of the same animal, morphologically similar tumours of all the three types of DNA distribution could be found. The increase in the hepatocyte ploidy level in the initial parenchyma by preliminary repeated treatments with CCl4, had no effect either on the occurrence of tumours, or on their ploidy level. No correlation was found between the DNA content, the size and histological structure of tumours.

Animals↗
PubMed1983

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. The present study was undertaken to reveal the potential mutagenic properties of prospidine, using regenerating mouse liver as rapidly proliferating cell system. Animals were given a single (900 or 1500 mg/kg) or daily (200 mg/kg for 9 days) injections of prospidine before or after partial hepatectomy. The mitotic activity, the duration of the cell cycle periods and the frequency of chromosome aberrations in ana-telophase were determined. The data show that unlike other alkylating drugs prospidine fails to suppress cell proliferation or to induce marked chromosome-breaking effects. The only mild effect observed was some prophase and prometaphase prolongation.

Animals↗
PubMed1982

[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. The proliferation pattern in the liver was shown to change during cancerogenesis. Unlike normal, a great number of cells were not polyploidized but were reproduced. As regards the cell content, the three adenomatous nodes examined differed from the surrounding parenchyma and from each other. On the whole, the degree of polyploidy in the nodes was much lower despite the fact that the population contained all the cell types, uni- and binuclear cells, up to those with the DNA content of 32c. All these cells and those from the surrounding liver were involved in proliferation. The cellular sources of nodular formations are discussed.

Animals↗
PubMed1982

[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. The ploidy level sharply increased. Aberrant cells were the most polyploid ones (16c, 32c). The DNA-fuchsin content in these aberrant polypolid cells decreased by 10--15% due to degrading and non-replication of DNA in the micronuclei.

Alkylating Agents↗
PubMed1980

Mitotic polyploidization of mouse heart myocytes during the first postnatal week.

Polyploidization of myocytes in the cardiac ventricle of mice occurs predominantly during the first week of the postnatal life. Using isolated cells it was shown that about 70% of the cardiomyocytes become binuclear at this time (2c x 2), while 10% are mononuclear but contain 4c of DNA, where c was the haploid level of DNA. About 2% of the cell population were reprsented by 4c x 2 or 8c cells. Cytophotometry of Feulgen-stained DNA in 14C-thymidine-labeled nuclei has shown that the cells that enter the mitotic cycle are mainly diploid. After mitosis (30 h or more after thymidine application) the label was found predominantly in 2c x 2 and 4c cell types. Comparison of the curves presenting dynamics of labeled mitoses and the accumulation of labeled binuclear cells reveals that binuclear 2c x 2 cells are formed by acytokinetic mitosis. The formation of 4c mononuclear cells is accomplished via other types of mitotic arrest; this may be due, for example, to a block in the pro- or metaphase. Only very rare cases of cytotomy were detected and the number of newly formed 2c cells was very low. It is concluded that cell multiplication is practically arrested at this period of life, and growth of the ventricular mass is due to polyploidization of virtually all cycling cells, while their number remains unchanged. Mechanisms and functional significance cardiomyocyte polyploidization are discussed.

Animals↗
PubMed1980

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. The DNA-synthesis time was assessed by DNA photometry combined with 3H-TdR autoradiography on the same nucleus. The DNA-content in Dipin-pretreated nuclei was doubled after 26 h, approximately three times longer than in the controls. Mitoses were completely absent during the first 2-4 days. They were observed subsequently for up to 2 months but with varying frequency. The frequency of binucleated hepatocytes remained constant during liver regeneration. Hence, pretreatment of resting liver with Dipin altered the kinetics of cell proliferation following partial hepatectomy. Delay in division resulted primarily from an increase in the DNA-synthesis time and a prolonged block of the transition from G2 to mitosis. No changes in the duration of the prereplicative period and in the size of the proliferative pool were noticed. The increase of the mitotic cycle time led to synchronization of the cell population. About a half of the hepatocytes were seen in the S phase by the end of the second day and by the end of the third day about 80% of the cells had passed into the G2 phase.

Alkylating Agents↗
PubMed1980

[Polyploidization mechanisms of the cardiac myocytes in the mouse].

Ventricular cardiomyocytes of 5-6 day-old mice are mostly polyploid. At this time 60% of the cardiomyocytes become binuclear and another 10% mononuclear polyploids. The binuclear cardiomyocytes emerge as a result of acytokinetic mitosis, while mononuclear tetraploids as a result of the cessation of the mitosis at the initial stages.

Animals↗
PubMed1980

[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. The upper limit of polyploidization reached 64 n. The maximum mean ploidy amounted on the average to 11.1 n. for the nucleus and 12.5 n for the cell. These values were 2.8 and 2.2 higher, respectively, than the initial ploidy level. Proliferative potencies of polyploid hepatocytes and the mechanisms of retention of an exceedingly small number of diploid cells during intensive reparative liver growth are discussed.

Animals↗
PubMed1979

[Polyploidizing mitoses and the biological meaning of polyploidy in liver cells].

The ontogenetic polyploidization of hepatocytes is regarded, within which normal mitoses are changed to polyploidizing mitoses, and diploid hepatocytes transform into polyploid mono- and binuclear cells. A new hypothesis is put forward of the biological significance of the liver cell polyploidy. The hypothesis takes into account a high level of spontaneous chromosomal aberrations in mitotic hepatocytes. The chromosome structural changes interfere with mitosis resulting in the chromosomal imbalance. Polyploidy bestows for hepatocytes a tolerance towards a chromosomal imbalance. Some implications of the hypothesis are discussed: unbalanced genome of hepatocytes after the treatment with mutagens and mitotic stimulators; the reasons of liver cell polyploidy differences in mammalian species; mechanisms of radioresistance of hepatocytes. Chromosomal imbalance of polyploid hepatocytes is assumed to be the basis for wome chronic liver diseases in man.

Animals↗
PubMed1979

[Heterogeneity in the distribution of cytochrome P-450 in the liver lobule revealed on exposure to carbon tetrachloride].

A comparative study was made of cytochrome P-450 content and the histological pattern of the development and elimination of necrotic foci arising in the liver of CBA mice after inhalation of CCl4 vapour. Two hours after the inhalation the content of cytochrome P-450 was reduced by a factor of 1.7, and in 17, 24, and 48 hours--by a factor of 6. The necrotized area was about 40% of the total liver lobe area. It is supposed that the selective (CCl4) damage of the central lobe hepatocytes was related to the marked differences between the cytochrome P-450 content in different areas of the lobe.

Animals↗
PubMed1979

[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. No phenomenon of unbalanced growth was recorded. No changes in duration of prereplicative period, or in the volume of proliferative pool were recorded. The increase of mitotic cycle periods resulted in the cell population synchronization: by the end of the second ay more than a half of hepatocytes were in S-period, by the end of the third day about 80% of cells passed to G2-period.

Alkylating Agents↗