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Biomedical subjects

L Holczinger

Publications and source records attributed to L Holczinger.

At least 19 recordsLinked to original sources
PubMed1988

Changes in the polyamine and nucleotide metabolism of P388 leukemia cells treated with DL-alpha-difluoromethylornithine in culture.

Influence of DL-alpha-difluoromethylornithine (DFMO) treatment on the growth kinetics, labelling index, extra- and intracellular polyamine and nucleotide concentrations was monitored in cultured P388 leukemia cells. A substantial decrease of cell proliferation was observed when the cells were continuously treated with 1-5 mM DFMO. Depletion of cellular polyamines, mostly of putrescine and spermidine, was seen with a concomitant but delayed increase of spermidine and spermine levels in the culture medium. Changes of DNA content and of labelling index of untreated and treated cells seem to indicate that DFMO arrested cells in G1/S transition. The results presented here provide additional in vitro evidence on the characteristic changes in the metabolic imbalance of ornithine in tumor cells induced by DFMO via inhibition of ornithine decarboxylase and ornithine carbamoyl transferase activities.

Animals↗
PubMed1988

Permanent metachromatic effect of 1,9-dimethyl-methylene blue on acidic mucopolysaccharides of mastocytes.

The 1,9-dimethyl-methylene blue (SERVA) has a very strong metachromatic reaction with sulphated mucopolysaccharides of mastocytes at pH = 1 (Tris-HCl buffer). This metachromasia is retained also at increasing pH (2.5-5), and is not affected either by the quality or by the concentration of the ions present (1/240 M Tris-HCl, and 0.2 M phosphate buffer). The smears do not need any special mounting medium, only Canada balsam. The metachromasia is preserved for a considerable length of time.

Animals↗
PubMed1988

Thymidylate synthetase and thymidine kinase activities and methotrexate cytotoxicity during growth of L1210 and Ehrlich ascites tumor.

The specific activities of TS and TK determined in the cytosols of Ehrlich and L1210 ascites tumor cells changed significantly during their logarithmic growth. In both tumors, the highest activity of TK was in early log phase while that of TS occurred in late logarithmic growth. The activity curves of TS were practically the same and those of TK were similar in the two tumors; however, the absolute values of the latter were different. TK/TS activity ratios in the early and late log growth of Ehrlich tumor were 20 and 2, in those of L1210 tumor 4 and 0.15 respectively. MTX cytotoxicity was considerable throughout the logarithmic growth of L1210 tumor, significantly higher values were observed however when TS activity increased. The variable degree of MTX cytotoxicity indicated an intracellular manifestation of the changes in TS activity determined in vitro. The different patterns for the specific activities of TS and TK, as well as, the parallel changes of TS activity and MTX cytotoxicity during tumor growth may be useful information for the antimetabolite research carried out with experimental tumors.

Animals↗
PubMed1987

Comparison of high-performance ion-exchange and ion-pair liquid chromatographic methods for the separation of tumour cell nucleotides.

Ion-exchange liquid chromatography (IELC) on a novel anion-exchanger, Polyanion SI HR 5/5, and the ion-pair technique (IPLC) using Hypersil ODS and/or MinoRPC reversed phases with tetrabutylammonium phosphate as pairing agent were compared for the separation of nucleotides. Modifications to the concentration gradient in IELC in the range 0.01-0.3 M ammonium phosphate resulted in the simultaneous separation of twelve to fourteen biologically important nucleotides. IPLC studies revealed that the capacity factors and resolution of nucleotides were more sensitive to the ionic strength than the methanol content. It was concluded that a well controlled ion concentration (0.08-0.09 M sodium chloride) should be maintained in the mobile phase and a linear methanol gradient ranging from 0 to 20% (v/v) was suitable for optimal resolution. Separations of four nucleotides and twelve nucleotides were further improved using a mixed-type reversed-phase column (C2/C18, MinoRPC). Using these complementary methods, it was possible to reveal the metabolic changes induced by different drug treatments (cyclophosphamide, DL-alpha-difluoromethylornithine) in the nucleotide pool of P388 leukaemia cells.

Animals↗
PubMed1986

In vivo effects of DL-alpha-difluoromethylornithine on the polyamine and nucleotide phosphate metabolism in P388/S leukemia cells.

In vivo effects of DL-alpha-difluoromethylornithine (DFMO) on the metabolism of polyamines and nucleotide phosphates were monitored in P388/S leukemia cells grown intraperitoneally in BDF1 inbred male mice. Inhibiting the ornithine decarboxylase (ODC) activity DFMO depleted putrescine and spermidine to 30-50 and 50-60%, respectively, and increased spermine to 25-60% compared with the controls, when given as 2% solution in drinking water of the tumor-bearing animals. DFMO treatment caused a parallel 56% elevation of total nucleotide content in tumor cells with distinct and significant increase of some nucleotide phosphates. The most pronounced alterations were shown in the intracellular UTP (202%), CTP (103%), ADP (92%) and ATP (71%) concentrations. Changes in polyamine and nucleotide phosphate metabolisms were dependent on tumor progression. A possible explanation of the metabolic events induced by DFMO is discussed.

Animals↗
PubMed1985

Rat liver-mediated degradation of dibromodulcitol.

The rate and extent of dibromodulcitol (DBD) conversion by 9000 g rat liver supernatant with an NADPH-generating system (S-9 mix) were studied using 3H-labelled drug. Results indicated that S-9 mix seemed to exert an initial protective effect delaying the solvolysis of DBD for about 30 min at 37 degrees C followed by rapid degradation into exclusively pharmacologically inactive products. Thus S-9 mix contained merely DBD as an effective agent; it amounted to less than 40% of the total radioactive compounds by 120 min. In the control mixtures the sovolytically produced effective drug content, i.e. the sum of DBD, 1,2-anhydro-6-bromo-6-deoxygalactitol (BrEpG), 1,2-5,6-dianhydrogalactitol (DAG) was 63%. Our results suggest the involvement of liver enzymes in the detoxification of DBD into inactive products. Therefore the antitumour effect of DBD cannot be attributed to its active BrEpG and DAG alone. The drug in its unchanged form may contribute to a somewhat greater extent to its cytostatic action than was believed before.

Animals↗
PubMed1985

Relationship between histological structure and lactate dehydrogenase isoenzyme pattern of rat mammary tumors induced by dimethylbenz(a)-anthracene.

Mammary gland tumors induced by 7,12-dimethylbenz(a)-anthracene (DMBA) in female Wistar rats could be divided into secreting and nonsecreting ones. Histological, histochemical, cytophotometric, and electron microscopic examinations yielded indirect evidence for the ab ovo malignant nature of the nonsecreting tumors but not for the secreting ones. Nonsecreting tumors showed high total lactate dehydrogenase (LDH) activity and a definite shift of the isoenzyme pattern toward isoenzymes containing M subunits compared to those of lactating mammary glands. Secreting tumors could be characterized by low total LDH activity and a moderate increase of M/H ratio. These biochemical results support the hypothesis that nonsecreting mammary tumors induced in rats--independently of metastatization and differentiation--have to be considered carcinomas while the secreting ones benign adenomas.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

Effects of bacterial endotoxins and their detoxified derivatives on serum and liver lipids in mice.

The influence of different endotoxins (lipopolysaccharides, LPS) obtained from Serratia marcescens 08, Escherichia coli 089, and their derivatives, detoxified either by partial hydrolysis or irradiation, on serum and hepatic lipids and on serum lipase activity in C57Black mice was studied. Endotoxic LPS elevated the serum total lipids and lipoproteins, particularly the very-low-density lipoproteins, and induced a reversible accumulation of triglycerides in the liver. Since nontoxic preparations did not cause such alterations, it is assumed that the toxicity of LPS is an essential factor in causing lipid metabolism disorder. A nearly identical increase in the lipase activity was detected in 5 to 10 hr in the sera of experimental animals treated by both toxic and nontoxic preparations. Results indicated the potential advantage of using detoxified derivatives of bacterial endotoxins in human therapy.

Animals↗
PubMed1984

Polyamine metabolism in P388 leukemia cells and in ascites tumor-bearing mice.

Alterations in ornithine decarboxylase (ODC) activity and in the polyamine and nucleic acid (RNA and DNA) concentrations were studied in P388 leukemia cells and in the host liver at different times after intraperitoneal inoculation of 5 X 10(6) tumor cells into BDF1 mice. ODC activity of leukemia cells had a maximum at day 5 after tumor transplantation. Cellular spermidine concentration declined significantly during the first 5 to 6 days. The RNA concentration of tumor cells changed parallel to that of spermidine. In the livers of ascites tumor-bearing mice ODC activity was 5- to 20-fold of control and had a maximum at days 5 to 6 after tumor cell inoculation. Spermidine concentration in the host liver increased, whereas spermine decreased gradually with tumor growth.

Animals↗
PubMed1984

Changes in lipoprotein lipase activity (LPLA) in tumor cells and tissues in mice bearing Ehrlich ascites tumor.

Lipid content and lipoprotein lipase activity (LPLA) of serum and various tissues of mice bearing Ehrlich ascites tumor have been studied. The growing tumor caused hyperlipidemia, depletion of adipose tissue, a slight increase of heart lipid content, lipid accretion in the tumor cells and a relative increase of free fatty acids and cholesterol in the ascites fluid. LPLA of the post-heparin plasma was higher in tumorous than in control mice. Tumor growth led to a marked decline of LPLA in the adipose tissue and an elevation in the heart. It declined slightly in the older tumor cells and increased in the ascites plasma of the same. It has been concluded that: a) decline in adipose tissue LPLA may play an important part in the development of hyperlipidemia and loss of body fat; b) increase of the heart LPLA proves insufficient for elimination of the piled up blood lipids during progression; c) LPLA in the ascites fluid may favour the hydrolysis of triglycerides entering the ascites fluid, which might account at least in part for the fatty acids made available to the tumor; d) LPLA detected in the tumor cells might also facilitate the assimilation of lipids by the tumor cells.

Adipose Tissue↗
PubMed1983

The effect of N-formylleurosine on DNA synthesis of Ehrlich ascites tumor.

Some of the vinca alkaloids are well known and widely used in clinical practice, in spite of their numerous side-effects. For the elimination of untoward side-effects semi-synthetic alkaloids have been produced. This work reports on N-formylleurosine (N-F-Leu), one of these agents. Its antitumour activity is, in many respects, similar to that of other, presently used vinca alkaloids; it causes metaphase block, the appearance of multinucleated cells and polyploidization. In addition to these effects, N-F-Leu induces significant new phenomena, namely, changes in the activity of thymidine kinase, a key enzyme of DNA synthesis as well as in thymidine incorporation, and reduces the proportion of cells in S phase in a relatively short period of time after treatment: 24-29 hr. Based on these observations, the reevaluation of the mechanism of action of vinca alkaloids has become possible.

Animals↗
PubMed1982

Incorporation of [7-3H]cholesterol into chromatin fractions of Ehrlich ascites tumour cells.

Incorporation in vivo of 3H-cholesterol into chromatin and its distribution among chromatin subfractions (DNA, histone, nonhistone proteins) of Ehrlich ascites tumour cells were studied. The majority of labeling appeared in the nonhistone fraction and only a slight incorporation or tracer amounts of 3H-labeling was found in the histone and DNA fractions. The 3H-labeling from 3H-cholesterol appeared predominantly in the non esterified cholesterol fractions. Our suggestion that neutral lipids--besides phospholipids--may also contribute to the regulatory functions of nonhistone chromosomal proteins needs further investigations.

Animals↗
PubMed1980

Investigation of vinca alkaloid-plasma membrane interactions by detergent gel chromatography.

Detergent gel chromatography was successfully applied for the separation of protein subunits and lipid micelles of [14C]Vincristine-treated and sodium dodecyl sulphate-solubilized liver cell plasma membranes. The elution profiles of solubilized membranes depended on the pore size of the commercial agarose and agarose-polyacrylamide gels used. It was found that most of the membrane-bound Vincristine was associated with the solubilized lipid micelles and only a very small proportion was bound to protein subunits.

Animals↗
PubMed1980

Complex evaluation of the effect of some cytostatic hexitol derivatives.

The antitumor effect of three structurally closely related alkylating hexitol derivatives (DBD, DAG, DiacDAG) was evaluated using a complex multi-parameter evaluation system. It comprised toxicology, action on ascites and solid tumors, as well as on subpopulations isolated by isopyknic centrifugation, cross-resistance and their action on chromatin components (DNA, histone, nonhistone proteins). The results indicate that in spite of their same mode of action, considerable differences could be observed in tumor specificity, inhibition of tumor growth and in their interaction with chromatin components. This multiparameter system seems to be very useful for comparative studies of other alkylating agents, especially for the evaluation of the effect of chemically closely related compounds.

Animals↗
PubMed1980

Heterogeneity of tumor cell populations.

Ascites tumor cell populations proved to be heterogeneous with respect to density. Subpopulations separated by isopycnic centrifugation differed from each other in several respects including cell cycle time, chromosome number and distribution and chemotherapeutic sensitivity. The results indicate that density separation is a useful technique to study the behavior of subpopulations within tumor and offers new possibilities in comparative experimental chemotherapy.

Animals↗
PubMed1979

Neutral lipids in DNA, histone and nonhistone fractions of Ehrlich ascites tumor cell chromatin.

Lipid content and composition of DNA, histone and nonhistone proteins of Ehrlich ascites tumor cell chromatin were investigated. All fractions contained varying amounts of lipids, mostly neutral lipids, with different quantitative distribution. The DNA fraction was characterized by elevated total cholesterol level (37%); the histone fraction by high glycerol ester content (62%); and the nonhistone protein fraction by high percentage of glycerol ethers (22%). The results suggest that neutral lipids are integral parts of tumor cell nucleoproteins.

Animals↗
PubMed1978

Neutral lipids in nuclei and chromatin fraction of young and old Ehrlich ascites tumor cells.

Determination of lipid content of Ehrlich ascites tumor cell nuclei devoid of the nuclear envelope and chromatin isolated from them revealed considerable amounts of neutral lipids present in both preparations. The neutral lipid content always exceeded that of the phospholipid. An age dependent accumulation of neutral lipids could also be observed. The chromatin fraction always contained relatively higher amounts of neutral lipids than the respective nuclei with a predominance of cholesterol esters.

Animals↗