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Biomedical subjects

V S Shapot

Publications and source records attributed to V S Shapot.

At least 37 records · Page 2Linked to original sources
PubMed1986

[Methodological approaches to the study of tumor and body tissue metabolism in vitro and in vivo].

The idea is put forward that in vitro measurements of the potential activity even of the key enzymes are not sufficient for correct evaluation of the rate of complex enzymic processes in vivo. The rate of the in vivo formation of final (not intermediate) products from the corresponding precursors is thought to be the most adequate criterion for it. The idea is substantiated by our studies on the glycolysis enzymes and RNA pyrimidine nucleotide synthesis. Such an approach permits gaining in particular, exact information on both features of the RNA synthesis in experimental tumours and mechanisms underlying a successful competition of the tumour and host tissues for RNA precursors. The latter phenomenon is one of manifestations of the tumour capacity to act as a trap for nitrogen.

Animals↗
PubMed1985

[Possible role of the T antigen in inducing chromosome aberrations in SV40 virus-transformed cells].

A possible role of the simian virus 40 T antigen in chromosome damages in transformed cells was examined. Two lines of Golden hamster embryonal fibroblasts, transformed by SV40 tsA30 and ts239 mutants (He30 and He239, respectively), were incubated at nonpermissive (40.5-41 degrees C) or permissive (33 degrees C) temperatures. Chromosome aberrations were registered in either subline after 3, 6, 9 and 12 weeks of cultivation under the above conditions. In the both cell lines kept at 33 degrees the frequency of aberrant metaphases and the number of chromosome breaks per cell increased drastically by week 3 of cultivation, and such a state was preserved up to week 12. The frequency of aberrant metaphases in cells cultivated at 41 degrees was maintained at the constant level (He239) or at slightly higher than that in the original culture (He30). The sublines He239, originally incubated at 33 or 40.5 degrees, were then shifted to 40.5 and 33 degrees, respectively. As a result the number of chromosome aberrations either decreased (33----40.5 degrees) or increased (40.5----33 degrees) as early as on day 2, and these patterns were stabilized at the level corresponding to the new conditions. We assayed the induction of DNA breaks in cells, grown at the permissive or nonpermissive temperatures, by using DNA sedimentation in the alkaline sucrose gradient. The DNA sedimentation peaks of cells cultured at 37 and 41 degrees coincided, whereas the DNA of cells cultured at 33 degrees was represented by shorter fragments.

Animals↗
PubMed1985

[Induction of chromosome aberrations by the T antigen of the SV40 virus introduced into the cells using liposomes].

A purified SV40 T antigen introduced into hamster cells by means of liposomes accumulated in the nuclei within 10 h and persisted there further as long as 10 to 12 h. Within the first day after cell treatment with T antigen numerous chromosome aberrations including breaks, translocations and gaps were observed in the cells. The number of aberrations slightly reduced by the 2nd day followed by restoration of the normal cell karyotype by the 5th day. Removal of T antigen incorporated into liposomes by a specific immunosorbent or heat inactivation of T antigen abolished the clastogenic effect. It is suggested that induction of chromosome aberrations might activate sell protooncogenes and thus serve a genetic basis of tumor progression.

Animals↗
PubMed1985

[Change in the strength of DNA-protein binding in T- and B-lymphocytes of the spleen of C3HA mice during chemical hepatocarcinogenesis].

The tightness of DNA-protein binding in the nuclei of mouse spleen T- and B-lymphocytes was assessed, using nucleoprotein celite chromatography, and changes in the number of T- and B-suppressors in the course of o-AAT-induced chemical hepatocarcinogenesis were studied. Attenuation of DNA-protein bonds in T-lymphocytes at the early stages (up to 3 months) was observed, and by the time of hepatoma formation (8 months) about 50% of T-lymphocyte DNA was loosely bound to proteins, which is a typical feature of quiescent cells. In B-lymphocytes attenuation of DNA-protein interaction was only observed by the 8th month of carcinogenesis. By the time of hepatoma formation the number of T-suppressors in mouse spleen increased 2.8-fold, while the number of B-suppressors in lymph nodes remained unchanged.

Animals↗
PubMed1985

[Aggregation of fragmented chromatin associated with the synthesis of products of its treatment with nuclease].

Isolated cell nuclei were incubated with nucleases followed by extraction of chromatin with a low salt buffer. With an increase of nuclear chromatin degradation with DNAse I or micrococcal nuclease, solubilization of deoxyribonucleoprotein (DNP) by a low salt buffer increases, reaching a maximum upon hydrolysis with 2-4% nuclear DNA and then decreases appreciably after extensive treatment with nucleases. Soluble fragmented chromatin aggregates in the course of treatment with DNAase. I. Addition to gel chromatin preparations of exogenous products of nuclease treatment of isolated nuclei leads to its aggregation. Pretreatment of nuclear chromatin with RNAase prevents solubilization of DNP by low ionic strength solutions. Some experimental data obtained with the use of severe nuclease treatment are discussed; for a correct interpretation of these data the aggregation of fragmented chromatin by products of its nuclease degradation should be taken into consideration.

Animals↗
PubMed1984

Turnover of [14C]thiamin and activities of thiamin pyrophosphate-dependent enzymes in tissues of mice with Ehrlich ascites carcinoma.

Turnover of [14C]thiamin was studied in mice with Ehrlich ascites carcinoma fed a thiamin-deficient diet and injected with 5 or 2 micrograms/mouse of the labeled vitamin. The process of conversion of [14C]thiamin to thiamin pyrophosphate (TPP) was monitored by measuring the activities of transketolase, pyruvate dehydrogenase, and oxoglutarate dehydrogenase. The amount of coenzyme-unsaturated apotransketolase was assessed by measuring the TPP effect--determining transketolase activity with and without the addition of TPP in vitro. Tumor growth was accompanied by thiamin deficiency, manifested in an increase in [14C]thiamin incorporation into the host tissues and the absence of saturation of the tissues with the labeled vitamin over 13 days. Increased values for the turnover coefficients, reduction of thiamin-dependent enzyme activities, elevation of the TPP effect, and a decrease in urinary excretion of the radioactive products also provided evidence for a disturbance in thiamin metabolism. The severity of the disturbance in thiamin metabolism during malignant tumor growth was directly related to the dose of the exogenous vitamin.

Animals↗
PubMed1984

[Induction of the replicative synthesis of DNA by SV40 virus T antigen introduced into cells using liposomes].

The role of virus SV40 T-antigen in the induction of cell DNA synthesis during its incorporation into cell liposomes was studied, using monolamellar liposomes obtained by phase reversal with incorporated highly purified T-antigen. Immunofluorescence studies revealed that T-antigen effectively penetrates inside the cells and after 10 hours is accumulated in the nuclei, where its level remains unchanged for 24 hours. Injections of purified T-antigen into the renal cells of serum-starved CV1 monkeys resulted in an almost 10-fold increase in the number of DNA-synthesizing cells 18 hours after the exposure. The same effect was observed during stimulation of a 10% serum culture. Removal of T-antigen from the preparation by specific immunoadsorption eliminated this effect. Centrifugation of cells grown in the presence of bromodeoxyuridine in a CsCl gradient was used to demonstrate the replicative type of cell DNA synthesis during T-antigen induction.

Animals↗
PubMed1984

[Changes in purine metabolism and in the immune response in the thymic and splenic lymphocytes of C3HA mice during chemical hepatocarcinogenesis].

The activities of adenosine deaminase, purine nucleoside phosphorylase, membrane 5'-nucleotidase and DNA content in thymus and spleen lymphocytes as well as the immune function of T and B lymphocytes of the spleen of C3HA mice with o-AAT-induced hepatomas were studied 1, 3 weeks and 3, 8, 12 months after o-AAT treatment was instituted. In the early stages of the hepatocarcinogenesis (up to 3 months), the elevation of the activity of all the enzymes and DNA content in thymocytes and T and B lymphocytes was observed. These changes coincided with the enhancement of the immune responses that manifested in the increased content of PFC, EA-RFC and high response to PHA and Con A. In the late stages, the decreased activities of purine nucleosides and nucleotide metabolizing enzymes correlated with disturbances of lymphocyte differentiation and lowering of the host immune response.

Animals↗
PubMed1984

[Metabolic factors determining the selective enhancement of the effect of ionizing radiation on tumors].

Two alternative approaches to enhance the damaging effect of X-rays on radioresistant tumours are discussed. One of them, hypoxyradiotherapy, suggests a preferential protection of normal host tissue, the other, short-term hyperglycemia, is directed to a selective intensification of tumour destruction. Both approaches take into account peculiarities of tumour metabolism. Theoretical considerations are put forward and experimental data are described elucidating the mechanisms of the selective action of hyperglycemia on the tumour and specifying the conditions which significantly enhance the antitumour radiation effect. In particular, a way to enhance the postradiation effect on tumour cells results in their interphase death. A combined use of gas hypoxia, hyperglycemia and hyperthermia is substantiated.

Animals↗
PubMed1984

[Bioelectric activity of the brain and glucocorticoid production in patients with hematologic malignancies].

A parallel study of bioelectrical activity of the brain and urine excretion of 17-hydroxycorticosteroids was carried out in 107 patients with various malignant tumors of hemopoietic tissue before, during and after treatment. In all of them, electroencephalography showed excitation of the hypothalamus, the central component of the hypothalamo-pituitary-adrenal system. Moreover, the patients revealed a significant increase in the excretion of 17-hydroxycorticosteroids that pointed to the activation of the peripheral component--the adrenal cortex. Activation of both central and peripheral components suggests that its intermediate component--the pituitary--is activated in patients with hemopoietic system neoplasms, too.

17-Hydroxycorticosteroids↗
PubMed1984

[Relation of proliferating to nonproliferating spleen cell populations during the development of Rauscher leukemia and after loading the mononuclear phagocyte system with colloidal gold].

Undulatory changes in the ratio of proliferating to quiescent spleen cells of (C57BL/6j X DBA/2)F1 male mice were revealed in the course of Rauscher's leukemia development by means of nucleoprotein-celite chromatography. Administration of colloidal gold particles for the purpose of the functional loading of the mononuclear phagocyte system (MPS) induced a temporary diminution (for several hours) of the proliferating cell percentage and the DNA synthesis rate. Then the number of proliferating cells returned to normal (by 24 hours), with the DNA synthesis rate exceeding the basic level. The data obtained point to the dependence of tumor cell proliferation on the MPS in Rauscher's leukemia.

Animals↗
PubMed1983

[Stages of the interaction of steroid hormones with intranuclear acceptor sites of Morris hepatoma cells].

The maximal amount of specifically bound triamsinolone acetonide (TA) penetrates into Morris hepatoma cells at initial steps of hormonal induction. This amount is gradually decreased during incubation of the cells with the hormone. As the incubation time rises, the inhibition of [3H]TA binding to the nuclear fraction induced by an excess of the non-labelled hormone is further decreased, which is paralleled with deceleration of the [3H]TA efflux from the nuclei to a hormone-free medium. After removal of the hormone the cells retain their ability to induce the synthesis of tyrosine aminotransferase for 10 hours, although after 3 hours the amount of the bound hormone falls down to 20-25% of the original level. The rate of further deinduction of tyrosine aminotransferase synthesis depends on the incubation time, i.e. in the cells preincubated with TA for 10 min the deinduction occurs at a slower rate than in the cells preincubated with the hormone for 48 hours. The increase in the amount of specifically bound TA 10 min after hormone addition leads to augmented synthesis of tyrosine aminotransferase which surpasses the synthesis providing for the maintenance of maximal induction. An addition of actinomycin D to a hormone-free medium containing the cells preincubated with TA for 48 hours prevents the deinduction. It is assumed that Morris hepatoma cells contain an actinomycin D-sensitive feed-back mechanism which controls the concentration and distribution of specifically bound intranuclear TA depending on hormonal response.

Animals↗
PubMed1983

[Biochemical criteria of mammalian cell sensitivity to glucocorticoids].

The resistance of Morris hepatoma cells strain 8994 to glucocorticoids which lack hormonal induction of tyrosine aminotransferase synthesis was studied. The cells of Morris hepatoma 7777 were used as a sensitive strain by a criterion of the enzyme synthesis. Using two-dimensional polyacrylamide gel electrophoresis, it was demonstrated that, i) in the cells of the "resistant" Morris hepatoma strain 8994 glucocorticoids change the rate of synthesis of at least five proteins, ii) two of these proteins are common for both cell strains, while the other ones are individual for each line, iii) in the cells of Morris hepatoma 8994 tyrosine aminotransferase is not controlled by glucocorticoids, iiii) glucocorticoids may not only control the activated genes but also the genes whose expression is suppressed. It was assumed that in the absence of disturbances in the receptor apparatus the resistance of any cell population to glucocorticoids can only be established by the use of a great variety of experimental approaches. The resistance of a cell population to the hormones cannot be judged upon by an analysis of the intensity of synthesis of one or even several proteins.

Animals↗
PubMed1983

[Interrelations and trigger mechanisms of homeostatic disorders in a tumor-bearing host].

A concept is substantiated that the most common feature of all malignant tumors would be their interference with host metabolism inducing various biochemical, endocrine, and immune disturbances of the host homeostasis which underlies certain neoplastic syndromes. The capacity of malignant tumors to exert hypoglycaemic pressure on the host functioning as a chronic stress factor leads to the activation of the hypothalamus-hypophysis system along with the stimulation of endogenous glucose formation from amino acids and glycerol, an energy-consuming process. The compensatory role of the stimulated lipolysis supplying, in addition to glycerol, free fatty acids and ketone bodies for host tissues as energy sources is emphasized. The adaptative nature of reduced insulin secretion and glucose tolerance in the tumor-bearing host facilitating the synergistic effect of glucagon, catecholamines, and glucocorticoids counteracting hypoglycaemic pressure of the tumor is suggested. A general scheme of relationships between the disturbances of the host homeostasis and their trigger mechanisms is outlined.

Adult↗
PubMed1983

[Possible reasons for decrease in the proliferating activity of the rat thymus after a single injection of glucocorticoids].

A single injection of triamcinolone-acetonide evoked multiple changes in adrenectomized rat thymuses, e.g. decrease of DNA polymerase and thymidine kinase activities, incorporation of [3H]thymidine into DNA and fragmentation of chromatin. The decrease of proliferating activity of thymus was preceded by inactivation of cytoplasmic DNA polymerase responsible for DNA replication. Fragmentation of DNA caused by double strand ruptures at the linkage sites affected primarily the non-proliferating thymocytes. Incubation of nuclei isolated from the thymuses of control and hormone-treated animals in Ca2+ and Mg2+-containing media increased the level of low molecular weight compounds in them. It was assumed that the inhibiting action of triamcinolone-acetonide on cytoplasmic DNA polymerase prevents the involvement of proliferating thymocyte subpopulation in a new generation cycle and provides for their terminal differentiation and decay, eventually resulting in fragmentation of DNA.

Adrenalectomy↗