[Changes in various biochemical indices and ultrastructure of ascites tumors after combined administration of cyclophosphamide and levorin]. / Izmenenie nekotorykh biokhimicheskikh pokazatelei i ul'trastruktury astsitnykh opukholei pri sochetannom vozdeistvii tsiklofosfana i levorina.

The fractional composition of chromatin proteins and an electron-microscopic pattern of cell ultrastructure of the Ehrlich ascite tumours and ascite lymphoma NK/Ly were studied when suppressing their growth by a combined action of cyclophosphane and polyene antibiotic. Changes in the fractional composition of chromatin proteins were found under the effect of levorin. A sharp increase in this effect and summation of heterogeneous morphological changes provoked by each of the preparation occur under a combined application of the preparations.

[Molecular mechanism of combined effect of amphotericin B and cyclophosphamide on a virus-induced neoplastic process]. / Molekuliarnyi mekhanizm sochetannogo deistviia amfoteritsina B i tsiklofosfana na virusindutsirovannyi neoplasticheskii protsess.

Study of an experimental neoplastic process induced by virus type strains of Rous's sarcoma has shown that amphotericin B potentiates antineoplastic action of cyclophosphamide. Administration of cytostatin does not affect the fractional composition of chromatin proteins. Administration of polyene changes this indicator, the changes being greater after combined use of both drugs. The character of a considerable part of the abnormalities in the fractional composition of chromatin proteins indicates that chromatin had been exposed to proteolytic enzymes.

[Changes in the state of plasma membrane proteins of tumor cells exposed to a polyene antibiotic and cyclophosphamide]. / Izmenenie sostoianiia belkov plazmaticheskikh membran opukholevykh kletok pod vozdeistviem polienovogo antibiotika i tsiklofosfana.

The fractional composition of the proteins of the plasmatic membranes of the Ehrlich's tumor cells treated with various drugs was studied with the use of electrophoresis in polyacrylamide gel. It was shown that the character of the changes in the fractional composition of the plasmatic membrane proteins under the effect of levorin and cyclophosphamide was different. When the drugs were used in combination, summation of the changes induced by every drug alone was observed. Possible causes of the changes in the fractional composition of the membrane proteins are discussed.

[Biochemical analysis of the microvillose membranes of the small intestine mucosa of dogs after levorin administration]. / Biokhmicheskii analiz membran mikrovorsinok slizistoi obolochki tonkogo kishechnika sobak posle vvedeniia levorina.

The effect of oral levorin used for a prolonged period of time on the lipid composition and activity of alkaline phosphatase and invertase of the microvilli membranes of the small intestinal enterocytes of old dogs was studied. Higher ratios of cholesterol/phospholipids in the membranes and inactivation of alkaline phosphatase and invertase were noted in the old dogs as compared to the young ones. Exposure of the old dogs to levorin had a significant effect on the microvilli membranes of the intestinal epithelial cells. It was evident from a lower ratio of cholesterol/phospholipids in the membranes and stimulation of the alkaline phosphatase activity. It is supposed that the changes in the state of the microvilli membranes of the small intestinal mucosa due to levorin play a definite role in the mechanism of its hypercholesterolemic action.

[Effect of levorin on the chromatin of the prostate of dogs in its hypertrophy]. / Izuchenie vliianiia levorina na khromatin predstatel'noi zhelezy sobak pri ee gipertrofii.

The effect of prolonged oral use of levorin on chromatin from the hypertrophic prostate of old dogs was studied. It was found that the chromatin from the hypertrophic prostate of old animals was characterized by a decrease in the relative content of non-histone proteins, the melting temperature and hyperchromism value. The results of the electrophoretic analysis of the histone fraction composition showed its proteolytic degradation. The matrix activity of chromatin in the RNA-polymerase system remained unchanged. Administration of levorin had no effect on the structural and functional characteristics of the chromatin isolated from the hypertrophic prostate of the old dogs.

[Changes in the protein composition of nuclear membranes of canine kidneys induced by amphotericin B in vivo]. / Izmenenie soderzhaniia belkov iadernykh membran pochek sobak pri deistvii amfoteritsina B in vivo.

Intraveneous injection of amphotericin B significantly affects the protein composition of canine kidney nuclear membranes. Electrophoresis in polyacrylamide gel showed that injection of this antibiotic results in a considerable loss or complete disappearance of the histone fractions H1 and H4 (depending on the dose) and a decrease in the content of fraction H3 in the membrane proteins. The fractionation spectrum of other nuclear membrane proteins also shows deviations from normal. One of possible reasons for that is the increased enzymatic degradation of the proteins. It is also probable that the changes in the protein composition of nuclear membranes are due to the presence of sodium deoxycholate in the antibiotic drug and may be accounted for by the nephrotoxic effect of polyenoic antibiotics.

[Biochemical shifts in the nuclear membranes of the kidneys of dogs after the prolonged intravenous administration of amphotericin B]. / O biokhmicheskikh sdvigakh v iadernykh membranakh pochek sobak posle vnutrivennogo prodolzhitel'nogo vvedeniia amfoteritsina B.

The protein composition of the nuclear membranes of the dog kidneys after intravenous infusion of amphotericin B in a dose of 3 mg/kg and sodium desoxycholate in a dose of 1.2 mg/kg for 8 days was studied. It was found that administration of amphotericin B and sodium desoxycholate was accompanied by pronounced changes in the membrane proteins. The changes were evident from a decreased content of histones in the nuclear membranes, elimination of the high molecular components, a decreased quantitative content of some fractions and appearance of low molecular bands. The effect of sodium desoxycholate on the nuclear membrane proteins was shown to be less pronounced than that of amphotericin B. The significance of the data is discussed in connection with high toxicity of polyenic antibiotics. The data provide elucidation of the causes of the nephrotoxic effect of the polyenic antibiotics.

[Suppression of the damaging effect of amphotericin B on dog kidney lysosomes by amigluracyl]. / Podavlenie amigluratsilom povrezhdaiushchego deistviia amfoteritsina B na lizosomy pochek sobak.

The effect of amphotericin B and its combination with amigluracyl on the dog kidney lyzosomes was studied in vitro. It was found that on incubation of the lyzosomes with the antibiotic in a concentration of 1 gamma/ml the latter stimulated liberation of proteases from them. At the same time, when the lyzosomes were exposed to amphotericin B in combination with amigluracyl, a significant decrease in the rise of the proteolytic activity in the incubation medium due to the antibiotic was observed. It was found that the combined use of amphotericin B with amigluracyl resulted in an intensive inhibition of the enzyme activity; The data are indicative of the fact that amigluracyl decreases the damaging effect of the antibiotic on the dog kidney lyzosomes.

[Study of nystatin effect on nuclear proteases of dog kidney causing degradation of acid-soluble proteins of chromatin]. / Izuchenie vozdeistviia nistatina na iadernye proteazy pochek sobak, vyzyvaiushchie degradatsiiu kislotorastvorimykh belkov khromatina

A relationship between the previously observed degradation of dog kidney chromatin histones induced by polyene antibiotics, and a change in enzymatic activity of neutral histone protease or proteases localized on the outer nuclear membrane was studied. It was shown that in the course of proteolysis of chromatin isolated from the nuclei after treatment by Triton X-100 nistatin inhibits neutral histone proteases as can be evidenced from the amount of the amino groups formed and the data of electrophoretic analysis of chromatin histones. The inhibitory effect of nistatin is sharply enhanced with an increase in its concentration. It is found that in the course of proteolysis of chromatin isolated from the nuclei untreated with Triton X-100, nistatin increases the degree of acid-soluble protein degradation. The latter effect is probably due to the stimulation of the enzymatic activity of proteases localized on the outer nuclear membrane by nistatin.

[Effects of polyene antibiotics on the membranes of dog kidney isolated nuclei]. / O deistvii polienovykh antibiotikov na membrany izolirovannykh iader pochek sobak

The effects of amphotericin B and nistatin on the membranes of dog kidney isolated nuclei after their incubation with the antibiotics in question, have been studied. It is found that the polyene antibiotics, though they are superficially-active compounds, have no solubilizing effect on nuclear membranes and do not change their chemical composition. Electrophoretic study has revealed that nuclear membrane proteins, besides high- and low-molecular protein components, also contain a large amount of histones. The incubation of the nuclei with the polyene antibiotics results in marked changes in the fractional composition of nuclear membrane proteins, the most significant changes being induced by amphotericin B. It is assumed that polyene antibiotics induce proteolytic degradation of nuclear membrane proteins.

[Effect of amphoterecin B on the plasma membranes of a tissue culture of puppy kidney]. / Vliianie amfoteritsina B na plazmaticheskie membrany kul'tury tkani pochek shchenkov

The effect of amphotoericin B on the chemical composition of the plasmic membranes of the puppy kidney tissue was studied. It was shown that amphotericin B in a concentration of 10 Units/ml induced changes in the quantitative content of proteins, lipids and RNA in the chemical composition of the plasmic membranes. The effect of amphotericin B on the composition of proteins and lipids in the membranes was also studied. It was found with the method of electrophoresis in polyacrylamide gel that after exposure of the culture cells to the antibiotic significant shifts in the composition of the membrane proteins took place. According to the findings of thin-layer chromatography amphotericin B markedly changed the quantitative content of the fractions in the composition of lipids in the plasmic membranes. Significant deviations under the effect of the antibiotic were observed in the quantitative ratio of separate fatty acids contained in the lipids of the membrane preparations studied. On the basis of the results obtained it was supposed that the mode of action of amphotericin B on the cell was associated with impairement of the plasmic membrane structure by the antibiotic.

[Effect of polyene antibiotics on isolated dog kidney nuclei]. / Deistvie polienovykh antibiotikov na izolirovannye iadra pochek sobak

Effect of amphotericin B and nistation on caryoplasmic proteins, nuclear membrane-bound chromatin (DNPm) and soluble DNP (DNP0) from dog kidney isolated nuclei is studied in vitro. The yield of caryoplasmic proteins from nuclei is found to be increased during incubation with amphotericin B and nistatin, the content of some fraction in caryoplasmic proteins being decreased while their qualitative composition being unchanged. It is found that the treatment of nuclei with amphotericin B contributes the association of DNP particles with nuclear membrane and the increase of protein/DNA and RNA/DNA ratios in DNPm. No such effects are observed in the presence of nistatin. Both antibiotics do not affect protein/DNA and RNA/DNA ratios in DNP0 fraction. Polyene antibiotics are shown to change considerably the composition of acid soluble proteins in DNP0 and DNPm and in non-histone proteins in DNP0, and not to affect the content of lipids and their fatty acid composition in DNPm. The data obtained are of certain value for explanation of the mechanism of toxic effect of polyene antibiotics on animal cells.

[The effect of polyene antibiotics on fractions of DNP both bound and not bound to dog kidney nuclear membranes]. / Deistvie polienovykh antibiotikov na fraktsiiu DNP, sviazannuiu i ne sviazannuiu s iadernoi membranoi pochek sobak

Effects of amphotericine B and nistatine on nuclear membrane-bound DNP (DNPm) and free DNP (DNPf) from dog kidney are studied. Intravenous injection of amphotericine B resulted in the increase of binding of DNP particles with nuclear membrane: the content of DNA in DNPm fraction was 50-fold increased. The injection of nistatine did not affect DNP binding with nuclear membrane. Amphotericine B alone increased the protein-DNA ratio and decreased the RNA/DNA ratio in DNPf fraction. Both amphotericine B and nistatine sharply increased the protein/DNA ratio and practically did not change the RNA/DNA ratio in DNPm fraction. Amphotericine B produced considerable changes in temperature denaturation of DNA in DNPo, while nistatine produced no effect. Both antibiotics considerably changed the composition of acid soluble proteins in DNPm and DNPf, non-histone proteins in DNPf, and also they caused the changed and quantitative redistribution of separate lipid components in DNPm lipids. Polyene antibiotics are suggested to effect on animal cell nuclear structures.

[Effect of polyene antibiotics on plasma membranes of dog kidney]. / Odenístvii polienovykh antibiotikov na plazmaticheskie membrany pochek sobak

Effects of amphotericine B and nistatine on plasmatic membranes of dog kidney are studied. Intravenous injection of antibiotics resulted in the change of the chemical composition of plasmatic membranes: the content of proteins, lipids and RNA. The composition of membrane proteins and the quantitative ratio of separate fatty acids in lipids of plasmatic membranes also changed in the presence of amphotericine B and nistatine. It is suggested on the basis of the data obtained that the mechanism of action of polyene antibiotics in dog kidney cells is connected with the damage of membrane structures.