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A Jeney

Publications and source records attributed to A Jeney.

At least 73 records · Page 4Linked to original sources

Further studies on the biochemical characterization of the MC-29 virus derived transplantable hepatoma (VTH). I. Binding of 3H-cortisol to cytoplasmic receptor and DNA.

The molecular mechanisms underlying the failure of steroids to stimulate glucose-6-Pase and arylhydrocarbonhydroxylase activities in the MC-29-virus-derived transplantable hepatoma (VTH) were investigated. Following cellular uptake of 3H-Cortisol, its subcellular distribution, binding to a specific cytoplasmic receptor and the interaction between steroid-bound receptor and DNA were compared in VTH and in normal chicken liver. No appreciable difference was observed either in 3H-Cortisol uptake or in binding to cytoplasmic receptors. However, compared with normal liver, only half as much hepatoma steroid receptor was able to interact with DNA at the protein/DNA ratio of 60. This reduced DNA binding of VTH 3H-Cortisol-receptor was irrespective of the source of DNA (VTH or liver). It is concluded that one of the causes for abnormal gene regulation in VTH may lie at the level of DNA-protein interaction.

Animals↗

Effect of PGI2 in carbon tetrachloride-induced liver injury.

The hepatoprotective effect of prostacycline was studied after in vitro and in vivo CCl4 liver injury. It was found that PGI2 could partly restore the amino acid incorporation after in vitro CCl4 poisoning. In the in vivo system PGI2 was capable of decreasing the elevated SGOT levels and the accumulated triglyceride in the liver, and to increase hepatic glycogen content 24 hours after CCl4 injury.

Alanine Transaminase↗

The effect of dibromo-dulcitol and dianhydro-dulcitol (galactitol) on RNA synthesis in ascites tumor cells.

The mechanism of action on RNA synthesis of anticancer dibromo-dulcitol (DBD, NSC-104800) and dianhydro-dulcitol (DAD, or elsewhere dianhydrogalactitol, DAG, NSC-132313) was investigated. Rats, bearing Yoshida or Novikoff hepatoma ascites tumor cells sensitive to these drugs were treated with doses equivalent to half the LD50 value. Nucleolar RNA (noRNA) and nuclear RNA (nRNA) were pulse labelled with 3H-uridine, isolated and fractionated on sucrose density gradient. After 18 h treatment with either drug and after 3 h with DAD noRNA synthesis increased and the rate of ribosomal RNA (rRNA) precursor processing was enhanced. Investigation of low-molecular weight nRNAs (LMW nRNAs) (separated by polyacrylamide gel electrophoresis) showed increased synthesis and/or accumulation of RNA species (5S RNA, uridylic acid rich RNAs) related to rRNA synthesis. The tritium labelled drugs were bound to distinct fractions of nRNA, separated by sucrose density gradient ultracentrifugation, both in vivo and in vitro. This fact may be explained by the formation of intra-, or intermolecular crosslinking of pre-messenger RNA. The enhanced RNA synthesis might be interpreted as an alteration in the functions of nuclear proteins, involved in the regulation of gene transcription and processing of RNA precursors.

Animals↗

Morphological and biochemical study of the hepatoprotective effect of AICA-phosphate.

The hepatoprotective effect and the possible mechanism of action of AICA-phosphate (AIP) were studied. Both the morphological and biochemical data proved the protective i.e. the connective tissue reducing effect of AIP in cirrhotic rat liver. Labelled AIP incorporated very intensively into microsomal RNA, suggesting that the compound may take part in the de novo purine synthesis. The increased rate of protein synthesis can be the consequence of the incorporation into RNA, promoting the regenerative processes in injured cells.

Aminoimidazole Carboxamide↗

Chromatin proteins as a possible target for antitumour agents: alterations of chromatin proteins in dibromodulcitol treated Yoshida tumors.

The effect of dibromodulcitol (DBD) on Yoshida sarcoma chromatin components has been investigated. Measurements on the radioactivity of nuclear components after in vivo treatment with [3H]DBD for 1 h indicated preferential drug binding to the high molecular weight component of the nuclear residual acidic protein (non-histones) and also to Histone 1 (H1) (very lysine rich, F1). Two-hour DBD treatment resulted in partial degradation and reduced [3H]leucine incorporation into the same fractions of chromatin. However, 6 h after DBD treatment, the synthesis of the degraded chromatin proteins began and by 24 h was completed. During the same treatment period the composition of chromatin showed a remarkable alteration; 2 h after DBD treatment the amount of the nuclear residual acidic proteins relative to DNA decreased by approx. 50%, but returned to control value 24 h after drug treatment. This in conjunction with the data on [3H]leucine incorporation suggests that certain chromatin proteins are degraded and subsequently newly synthesised after DND treatment resulting in an exchange of chromatin components. The formation of a nucleohistone complex between H1 and DNA was inhibited by pretreatment of H1 and DBD, dianhydrodulcitol (DAD) and bischloroethylnitrosourea (BCNU).

Animals↗

Spontaneous and chemically-induced transformation of mouse fibroblasts in culture. Biochemical aspects of the transformed cells.

Fibroblast cultures were established from the lung tissue of CBA T6T6 mouse embryos. Lines characterized by infinite growth transformation (MFL) were used as untreated controls till the 21st and 29th passages, respectively. After that period, an unrestrained growth transformation developed spontaneously. The cell line was then designated as STMFL. At the 8th passage of an MFL, 20-methylcholanthrene (MC) treatment was performed. The treatment resulted in a cell line (MCMFL) characterized also by unrestrained growth transformation. The nuclear protein pattern obtained by two-dimensional gel electrophoresis showed differences between STFL and MCMFL. The activity of two microsomal enzymes - aryl hydrocarbon hydroxylase and ethylmorphin demethylase - measured in the exponential growth stage of the cultures showed a decrease in the case of STMFL, compared to the MFL, and practically disappeared in the case of MCMFL.

Animals↗

Morphological and biochemical studies on the effect of agents with liver protecting properties.

The liver protective effect of Aicaphosphate in CC1(4)-induced acute, as well as CC1(4)-and thioacetamide-induced subacute and chronic liver damages is demonstrated. The effect of the protective drugs was studied in the forms of pre-, simultaneous and delayed treatment in acute and chronic liver damages induced by various toxic agents. The degree of liver damage was determined by morphological and biochemical methods, complementary to each other. For the completion of histological studies and morphometry used for the determination of the degree of fibrosis biochemical investigations are performed. In acute liver damage the determination of DNA, protein and lipid contents of the liver tissue and the radioactive aminoacid incorporation rate should be carried out with a simultaneous analysis of the serum enzymes. In chronic liver damage, the measurement of the hydroxyproline and DNA contents of the liver give useful data for the determination of the severity of the lesion and the effect of the protective drugs, respectively.

Acetamides↗

In vitro carcinogenesis studies on mouse fibroblast cells.

Fibroblast cell lines were established from pulmonary explants derived from inbred CBA T6T6 mouse embryos. Cell lines controlled for the absence of spontaneous transformation were treated with 20=methylcholenthrene (0, 1 microgram/ml). The altered biological characteristics were studied during the process of the malignant transformation by the comparison of the untreated and 20-methylcholanthrene pretreated cell populations: the loss of contact inhibition and the connection between the malignant transformation and the arylhydrocarbon hydroxylase enzyme activity were investigated. No changes in the cell proliferation rate could be found following malignant transformation, but an increased resistance against altered circumstances was observed. In the course of passages, a gradual decreases in aryl hydrocarbon hydroxylase activity of the untreated line was seen, which disappeared or significantly decreased following 20-methylcholanthrene treatment, compared to the controls.

Animals↗

Studies on in vitro carcinogenesis. I. Autoradiographic and biochemical study on the incorporation of labelled methylcholantrene into mouse embryonic cells.

The incorporation of radioactive labelled Methylcholanthrene into CBA/T6T6 mouse embryonic fibroblast cultures was studied by using light and electronmicroscopic autoradiographic and also liquid scintillation counting techniques. During 24 hrs treatment time at the applied Methylcholanthrene concentrations (0.01-2.5 mug/ml) the proportion of cells labelled with 3H-Methylcholanthrene and the number of grains above the cells showed a relationship with the duration of treatment and also with the doses. Up to 24 hrs all cells were labelled after treatment with 2.5 mug/ml whereas at 0.01 and at 0.1 mug/ml concentrations Methylcholanthrene could have been detected only 2 and 10% of the cell population resp. The presented results suggested that labelling index reached saturation level earlier than the average number of grains. Electronmicroscopic autoradiography revealed a rather even distribution of grains and there were no signs for preferential binding site of Methylcholanthrene. Biochemical separation showed that 59 and 44% of the radioactivity was bound to macromolecules at 1 and 24 hrs after commencing treatment resp.

Animals↗

The effect of dibromodulcitol on resting and dividing lymphoid cells.

The effect of dibromodulcitol (DBD) on the incorporation of labelled precursors into DNA and RNA fractions of PHA-stimulated human lymphocytes and of P388F lymphoma cells at various stages of their growth was studied. Both cell systems showed sensitivity to the drug within the concentration rage of 1-10 mug/ml. When DBD was added before phytohaemagglutinin (PHA), h.han RNA. In contrast, by adding DBD after PHA, RNA labelling was much more inhibited than DNA. In the latter case, the decrease in DNA labelling occurred only 24 h after drug treatment whereas RNA labelling was decreased 1 h after treatment. Levels of DBD which normally produced 30% inhibition in plating efficiency of P388F lymphoma cells affected uridine-5-T incorporation to a different extent at different stages of growth of the culture. Enhanced RNA labelling occurred in early exponential stage while at later stages of growth, RNA synthesis was depressed.

Adult↗

Biochemistry and enzyme induction in MC-29 virus-induced transplantable avian hepatoma.

For the biochemical characterization of a new transplantable hepatoma derived from the MC-29 virus-induced liver tumor, the macromolecular content and the inducibility of glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, and aryl hydrocarbon hydroxylase were compared in chicken liver and in this hepatoma. The alteration of the nucleocytoplasmic ratio was deduced from measurements of DNA, RNA, protein, and phospholipid contents of the whole cell homogenate and cell fractions. The increased nuclear and decreased cytoplasmic content of macromolecules suggests a dominancy of the nuclei in the tumor cells. Glucose-6-phosphatase and aryl hydrocarbon hydroxylase activities were lower by 60 and 80%, respectively, in the highly proliferating hepatoma than in the liver. In contrast, glucose-6-phosphate dehydrogenase activity increased in the hepatoma. However, enzyme inducers, such as methylcholanthrene, hydrocortisone, and insulin, were able to enhance the activity of these enzymes in the liver but had no stimulating effect on the hepatoma.

Animals↗