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Biomedical subjects

P Ove

Publications and source records attributed to P Ove.

At least 37 records · Page 2Linked to original sources
PubMed1980

Involvement of the lodothyronines in liver and hepatoma cell proliferation in the rat.

3,3',5-Triiodo-L-thyronine (200 microgram/100 g) is shown to be a potent liver parenchymal cell mitogen in the rat, and thyroidectomy is seen to severely inhibit hepatocyte proliferation in regenerating rat liver. Taken together, these observations point to a crucial role for the iodothyronine in liver cell hyperplasia. The growth rates of the transplantable Morris hepatomas 7777 and 5123tc are shown to be retarded in the surgically thyroidectomized-parathyroidectomized rat. This inhibition of tumor growth can be reversed by thyroid hormone administration. It has earlier been observed that the hypothyroid state induced in the rat by administration of propylthiouracil or radioactive iodine retarded the growth of the transplanted Morris hepatomas 7800 and 44, suggesting that these tumors were also thyroid dependent. Our results suggest that the thyroid hormones may play a similar role in the growth of liver cell-derived cancers as they do in normal hepatocyte proliferation.

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PubMed1979

Inhibition of tritiated thymidine incorporation in cultured cells by rat kidney extract.

KCl extract from rat kidney, rat liver, and Morris hepatomas inhibited [3H]thymidine incorporation into cultured cells. Tissues came from male inbred BUF rats. The most pronounced inhibition was achieved with the kidney extract. Protein synthesis was not inhibited during a 24-hour exposure of the cells to the inhibitor. Incorporation of [3H]deoxycytidine was inhibited, as was cell growth, when the kidney KCl extract was present for several days. [3H]thymidine incorporation was inhibited almost immediately after the addition of the extract. The inhibition was reversible. Regular [3H]thymidine incorporation was restored 24 hours after removal of the inhibitor, which was neither arginase nor a thymidine-degrading enzyme. The inhibitor was stable to heat (80 degrees C for 10 min) and resistant to trypsin, pronase, DNase, and RNase. Exposure of the extract to proteolytic enzymes, hyaluronidase, and neuraminidase resulted in a loss of inhibitory activity only after extensive dialysis of the treated extract. The inhibitor appeared to be a mucoprotein in which the carbohydrate moiety may be responsible for the inhibition. The KCl extract also inhibited RNA synthesis and DNA synthesis by the de novo pathway. The inhibition of phosphorylation of thymidine, however, appeared to be the primary action of the inhibitor.

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PubMed1979

Chromatin protein methylation in proliferating liver and hepatoma cells.

Chromatin protein methylation in proliferating liver cells and hepatomas was examined in vivo and in vitro. Methylation in vivo was estimated using 2-14 C-L-methionine and 3H-methyl-L-methionine. 3H/14C ratios were calculated for crude histone and nonhistone chromatin protein fractions and compared to those calculated for serum albumin. From this, determination of a methylation index was calculated using serum albumin as a standard. Results of this study indicate that both histones and nonhistone chromatin proteins are methylated to a greater extent in proliferating liver cells and in hepatomas than in control preparations. These observations are generally supported by our in vitro methylation studies. The results are discussed in terms of chromatin protein methylation and its possible relationship to DNA replication.

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PubMed1977

Effect of camptothecin and adriamycin on bleomycin-induced tritiated thymidine triphosphate incorporation in a rat nuclear system.

We investigated the effect of camptothecin and adriamycin on [3H]TTP incorporation and bleomycin-stimulated [3H]TTP incorporation in host liver and hepatoma nuclei of rats. Camptothecin neither stimulated nor inhibited incorporation in the regular nuclear incorporating system. Bleomycin stimulated incorporation to a much greater extent in host liver nuclei and slow-growing hepatomas than it did in the fast-growing hepatoma 7777. Addition of camptothecin to bleomycin stimulated incorporation of [3H]TTP even further. This camptothecin stimulation was slightly greater in hepatoma nuclei than it was in host liver nuclei. Adriamycin inhibited [3H]TTP incorporation in the regular system as well as the bleomycin-induced incorporation. Hepatoma nuclei were more sensitive to this inhibition than were host liver nuclei. Sucrose density gradients indicated that camptothecin caused DNA strand scissions in addition to those produced by bleomycin. Camptothecin alone produced some single-strand but no double-strand scissions. The action of bleomycin was dependent on sulfhydryl-reducing agents. Camptothecin could partially substitute for this requirement. Adriamycin did not produce DNA breaks as determined by neutral or alkaline sucrose density gradients. Despite complete inhibition of bleomycin-induced [3H]TTP incorporation, adriamycin did not prevent bleomycin-induced DNA breaks. The inhibitory effect of adriamycin might have been on the repair system.

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PubMed1977

Inhibition of growth of Morris hepatomas 7777 and 7800 by corn oil.

Intraperitoneal injection of trace amounts of corn oil prior to and following the injection of 40-50 mg of tissue from hepatoma 7777 or 7800 into the thigh of adult male Buffalo rats resulted in a marked decrease in the growth rate of both tumors. Exhaustive extraction of the corn oil with water indicated that the active component was not water soluble. Similar injections of safflower oil or isotonic saline had no effect on tumor growth rate. Analysis of the tissue phospholipid fatty acids revealed that the injected corn oil caused no change in the esterified fatty acids in this lipid fraction.

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PubMed1977

The effect of several antitumor agents on 3H-TTP incorporation in host liver and hepatoma nuclei.

Six different tumor antibiotics have been investigated in a nuclear incorporating system for their ability to inhibit 3H-TTP incorporation. Both host liver nuclei and nuclei prepared from two different Morris hepatomas have been used in the investigation. Three of these anti-tumor agents inhibit 3H-TTP incorporation equally in host liver and hepatoma nuclei, two preferentially inhibit incorporation in hepatoma nuclei and one stimulates incorporation preferentially in host liver nuclei. The effects of these compounds on nuclear DNA has been analyzed on neutral and alkaline sucrose density gradients. The nuclear incorporation system appears to be useful as a screening test system for potential anti-tumor agents.

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PubMed1977

Inhibition of bleomycin-induced [3H] thymidine 5'-triphosphate incorporation into liver and hepatoma nuclei by N-ethyl maleimide and daunomycin.

The addition of bleomycin to a nuclear incorporating system results in an increased incorporation of 3H-thymidine 5'-triphosphate (3H-TTP) into the DNA of liver and hepatoma nuclei. Bleomycin added to the nuclear incorporating system also produces scissions of DNA as determined by sucrose density gradient centrifugation of the extracted DNA. The action of bleomycin is dependent on the presence of sulfhydryl agents in the incubation mixture. Two compounds, N-ethyl maleimide and daunomycin, inhibit the bleomycin-induced incorporation of 3H-TTP preferentially. N-Ethyl maleimide inhibits bleomycin-induced activity in liver and hepatoma 7777 nuclei equally. Lower levels of daunomycin inhibit the bleomycin-induced activity in the hepatoma 7777 nuclei than are required to inhibit the activity in liver nuclei. The two compounds inhibit the bleomycin effect by different mechanisms. The addition of N-ethyl maleimide to bleomycin in the incubation system prevents bleomycin from causing breaks in the DNA. The addition of daunomycin, despite inhibition of bleomycin-induced 3H-TTP incorporation, does not affect the bleomycin-produced breaks in the DNA. N-Ethyl maleimide acts by binding to the DNA and by competing with a sulfhydryl agent for bleomycin-sensitive sites on the DNA. Daunomycin apparently inhibits a repair enzyme that is responsible for the increased incorporation following bleomycin treatment.

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PubMed1976

Evaluation of a serum protein in pregnant rats.

The increase of a serum protein in the circulation of rats during pregnancy has been described. The protein is different from the human pregnancy zone protein previously described. This new serum protein factor is present in normal rat serum and accounts for approximately 1% of the total serum protein. The protein factor disappears from the serum of animals bearing Morris hepatomas 7777 and 7800. The amount of factor diminishes as the tumors increase in size. The levels of this protein in the serum increased several fold during pregnancy with highest levels found shortly before parturition. Levels remained elevated for at least 12 days post partum. No corresponding increase in the levels of this serum factor in the fetal circulation was observed. Increased levels in the maternal circulation were due to an increased synthesis of this serum protein during pregnancy. A corresponding band was observed on polyacrylamide gels for normal human female and pregnant human sera or plasma. However, there was no increase during pregnancy as judged by polyacrylamide gel electrophoresis. Quantitative determination of the protein in human sera was not possible since the band corresponding to the serum protein in rats did not cross react with a rabbit anti-rat serum factor.

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PubMed1976

Synthesis and half-life of a serum factor in normal and tumor-bearing animals.

The synthesis and disappearance of a serum factor from the circulating blood of rats bearing Morris hepatomas 7777 or 7800 were described. We provided evidence that the factor was synthesized by the livers of normal rats and continued to be synthesized in tumor-bearing animals. Despite very low levels in the sera of tumor-bearing animals, the factor was synthesized at twice the rate in these animals compared to that in normal rats. The half-life of the total serum protein was 2 days in normal rats and 2.9 days in hepatoma 7777-bearing animals. The half-life of the serum factor, on the other hand, was 23 hours in normal rats but only 9 hours in hepatoma-bearing rats. This rapid disappearance of the factor from the circulating blood, despite an increased synthesis, accounts for the complete absence of the factor in the sera of hepatoma-bearing animals with tumor weights larger than the liver weights.

Animals↗
PubMed1976

Effect of bleomycin on [3H]Thymidine 5'-Triphosphate incorporation into host liver and hepatoma nuclei.

The effect of bleomycin on [3H]thymidine 5'-triphosphate ([3H]TTP) incorporation into isolated sucrose nuclei from host liver and Morris hepatomas has been compared. Bleomycin stimulates [3H]TTP incorporation 13-fold in host liver and hepatoma 16 nuclei, 8-fold in hepatoma 7800 nuclei, and 3-fold in hepatoma 7777 nuclei. Differences in the nuclear membranes are not responsible for the different response of the nuclei. Nuclei, denuded of their membranes by Triton X-100 treatment, give similar results to sucrose nuclei. Analysis of DNA extracted from liver or hepatoma nuclei incubated with bleomycin indicates that bleomycin produces scissions in the nuclear DNA and that some repair synthesis takes place. Incubation of nuclei with 111indium-labeled bleomycin shows an equal binding capacity of liver and hepatoma nuclei for bleomycin. Bleomycin also stimulates incorporation of [3H]TTP in a system using chromatin or calf thymus DNA as primer. Host liver or hepatoma chromatin incubated with a DNA polymerase extracted from normal rat liver nuclei is stimulated approximately to the same extent by bleomycin. When DNA polymerase extracts from host liver and hepatoma nuclei are assayed with calf thymus DNA as primer, bleomycin has a greater stimulatory effect on [3H]TTP incorporation with host liver DNA polymerase than with hepatoma DNA polymerase in the system. We suggest that a defect in the repair system in hepatoma nuclei is responsible for the relatively lower response to bleomycin.

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PubMed1975

Effect of a normal serum protein absent from hepatoma-bearing animals on cell cultures.

The effect of a serum factor purified from normal rat serum on growth and incorporation of 3-H-thymidine and 3-H-leucine was investigated with the use of 3T3 and L cells. The factor was not present in serum of hepatoma-bearing animals at a time when the weight of the hepatomas was equal to or greater than liver weight. The factor disappeared gradually from the serum of hepatoma-bearing animals, and the disappearance was proportional to the increase in the size of the hepatomas. Diminished amounts of the factor could be detected as early as 10 days after hepatoma transplant, and the factor was absent at 30 days after hepatoma transplant from the serum of rats bearing hepatoma 7777. Medium supplemented with 5% normal rat serum supported incorporation of lavel into 3T3 and L cells and growth of these cells, as did medium supplemented with 10% calf serum. Serum from hepatoma-bearing animals was only approximately equal to 50% as efficient as normal rat serum in supporting growth and label incorporation. The addition of purified factor to the serum from hepatoma-bearing animals restored the ability of the serum to support growth and label incorporation to between 70 and 90% of that found with normal rat serum as a medium supplement. The factor also enhanced incorporation of 3-H-thymidine following release of 3T3 cells from contact inhibition.

Animals↗
PubMed1975

Stimulatory effect of a serum factor on DNA synthesis in isolated hepatoma nuclei.

A serum protein present in normal rat serum and absent from the serum of hepatoma-bearing animals at advanced stages has a stimulatory effect on 3H-thymidine incorporation into hepatoma cells in suspension. Liver cells maintained in a similar suspension are not affected by the factor. The stimulation appears to be at the level of chromatin or DNA. Isolated membrane-denuded nuclei from Morris hepatoma 7777 incorporate more 3H-TTP when the factor is present in the incubation mixture. Nuclei from host liver are not stimulated. The factor also stimulates incorporation of 3H-TTP in a system using calf thymus DNA as primer and an extracted DNA polymerase. In this system incorporation is stimulated with DNA polymerase from both tissues, host liver and hepatoma 7777. It is concluded that the factor does not act on the DNA polymerase but on chromatin or DNA.

Animals↗
PubMed1975

DNA synthesis in membrane-denuded nuclei and nuclear fractions from host liver and Morris hepatomas.

Incorporation of [3H]TTP into membrane-denuded nuclei and fractions of these nuclei from host liver and Morris hepatomas has been compared. Treatment of sucrose nuclei with Triton X-100 removed 95% of the phospholipids and 15 to 20% of the protein. These membrane-denuded nuclei remained physically stable. The Triton X-100-extracted nuclei incorporated label into their DNA in nuclear-incorporating system similar to sucrose nuclei with their membranes intact. Triton X-100-treated nuclei from hepatoma 7777 incorporated six times more label and those from hepatoma 7800 incorporated three times more label than Triton X-100-treated host liver nuclei. Nuclei from the three sources incorporated more label when exogenous DNA was added to the incubation system, but the difference in incorporation between the hepatoma nuclei and the host liver nuclei disappeared. When Triton X-100-treated nuclei, prepared from a tumor-bearing animal given injections of [3H]thymidine for 10 min were fractionated on sucrose gradients after disruption by high Mg2+ concentration, the fractions from hepatoma 7777 nuclei contained six times as much label as the host liver nuclear fractions. Nuclear fractions prepared from unabeled hepatomas or host livers had DNA polymerase activity. The activity, however, is the same in fractions prepared from hepatoma 7777 or host liver nuclei. It is suggested that the nuclear membrane does not play an important role in nuclear DNA synthesis. It is further suggested that the increased incorporation found with hepatoma nuclei is dependent on a physical or chemical arrangement of components within the nucleus and not solely on different enzyme levels.

Animals↗
PubMed1975

Some biochemical characteristics of rat liver and Morris hepatoma nuclei and nuclear membranes.

Nuclei prepared from host liver and from Morris hepatomas 7777 and 7800 have been compared with respect to some of their biochemical characteristics. Several criteria were used to ensure that liver and hepatoma nuclei were of equal purity. These criteria include equal specific activity ratios (homogenate nuclei) for several marker enzymes. Phospholipids, proteins, and sialic acid content were compared in liver and hepatoma sucrose nuclei and in membrane and chromatin fractions obtained from liver or hepatoma nuclei. As determined by sodium dodecyl sulfate polyacrylamide electrophoresis, the only qualitative difference in protein that could detected was in 2 of the 4 nuclear fractions. There was an extra band in each of the 2 hepatoma fractions. Sialic acid was increased in hepatoma nuclei. In addition, a fraction containing most of the inner nuclear membrane from liver nuclei had no sialic acid, whereas the equivalent hepatoma fraction did have sialic acid. Total phospholipids were increased in hepatoma nuclei. This increased phospholipid concentration in hepatoma nuclei as compared to liver nuclei was apparent with sucrose nuclei, citric acid nuclei, membrane-denuded nuclei, chromatin, and nuclear fractions. Determination of the percentages of individual phospholipids making up the total phospholipids extracted revealed that the only significant change in the phospholipid composition of hepatoma nuclei was an increase in sphingomyelin. A large amount of this sphingomyelin was found to be associated with chromatin. The possible significance of chromatin-associated phospholipids is discussed.

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