scholarly journals THE INCORPORATION OF FORMATE-C14 INTO THE NUCLEIC ACIDS OF RATS WITH REGENERATING LIVER AND NOVIKOFF HEPATOMA

1959 ◽  
Vol 37 (1) ◽  
pp. 1405-1416 ◽  
Author(s):  
J. C. Nixon ◽  
S. H. Zbarsky

A study was made of the incorporation in vivo of formate-C14 into the purines and thymine of regenerating liver and Novikoff hepatoma in the rat, during the period of maximum mitotic activity of these tissues. The effects of these tissues on one another and on certain host tissues were also studied. The maximum mitotic frequency of Novikoff hepatoma was observed on the 4th day of growth following transplantation. This tumor caused a decrease in formate incorporation into the nucleic acid purines and thymine of the host's spleen and intestinal mucosa but had little effect on liver. The results also indicated that the uptake of formate by the RNA adenine of spleen and intestinal mucosa and the DNA thymine of intestinal mucosa was diminished by the presence of regenerating liver. The simultaneous presence of both regenerating liver and Novikoff hepatoma generally lowered the incorporation of formate-C14 into the nucleic acids of the host spleen and intestinal mucosa. It was observed further that the utilization of formate by the nucleic acids of Novikoff hepatoma and regenerating rat liver was decreased in animals containing both of these rapidly dividing tissues.

1959 ◽  
Vol 37 (12) ◽  
pp. 1405-1416 ◽  
Author(s):  
J. C. Nixon ◽  
S. H. Zbarsky

A study was made of the incorporation in vivo of formate-C14 into the purines and thymine of regenerating liver and Novikoff hepatoma in the rat, during the period of maximum mitotic activity of these tissues. The effects of these tissues on one another and on certain host tissues were also studied. The maximum mitotic frequency of Novikoff hepatoma was observed on the 4th day of growth following transplantation. This tumor caused a decrease in formate incorporation into the nucleic acid purines and thymine of the host's spleen and intestinal mucosa but had little effect on liver. The results also indicated that the uptake of formate by the RNA adenine of spleen and intestinal mucosa and the DNA thymine of intestinal mucosa was diminished by the presence of regenerating liver. The simultaneous presence of both regenerating liver and Novikoff hepatoma generally lowered the incorporation of formate-C14 into the nucleic acids of the host spleen and intestinal mucosa. It was observed further that the utilization of formate by the nucleic acids of Novikoff hepatoma and regenerating rat liver was decreased in animals containing both of these rapidly dividing tissues.


1958 ◽  
Vol 36 (11) ◽  
pp. 1185-1192 ◽  
Author(s):  
S. H. Zbarsky ◽  
Aiko Hori ◽  
Barbara S. Findlay

A study was made of the incorporation in vivo of C14-labelled formate into purines and pyrimidines of the nucleic acids of various tissues of normal rats and rats bearing the Novikoff hepatoma. The purines of the intestinal mucosa and the hepatoma had the highest specific activities, followed in descending order by those of spleen, kidney, testes, and liver. The pyrimidines of the mucosa and hepatoma also exhibited comparatively high specific activities. It was felt that the incorporation of radioactivity by a given tissue was related to its rate of cell renewal and that the present findings did not indicate a difference between tumor and normal tissue with respect to mechanisms involved in the biosynthesis of the nucleic acids. The results indicated that the tissue nucleic acids of the tumor-bearing animals incorporated more radioactivity than did those of normal rats. Chemical degradation of the radioactive purines showed that part of the radioactivity was derived from the injected C14-formate and part from C14O2 formed by metabolic oxidation of the formate.


1958 ◽  
Vol 36 (1) ◽  
pp. 1185-1192 ◽  
Author(s):  
S. H. Zbarsky ◽  
Aiko Hori ◽  
Barbara S. Findlay

A study was made of the incorporation in vivo of C14-labelled formate into purines and pyrimidines of the nucleic acids of various tissues of normal rats and rats bearing the Novikoff hepatoma. The purines of the intestinal mucosa and the hepatoma had the highest specific activities, followed in descending order by those of spleen, kidney, testes, and liver. The pyrimidines of the mucosa and hepatoma also exhibited comparatively high specific activities. It was felt that the incorporation of radioactivity by a given tissue was related to its rate of cell renewal and that the present findings did not indicate a difference between tumor and normal tissue with respect to mechanisms involved in the biosynthesis of the nucleic acids. The results indicated that the tissue nucleic acids of the tumor-bearing animals incorporated more radioactivity than did those of normal rats. Chemical degradation of the radioactive purines showed that part of the radioactivity was derived from the injected C14-formate and part from C14O2 formed by metabolic oxidation of the formate.


1963 ◽  
Vol 41 (11) ◽  
pp. 2237-2247 ◽  
Author(s):  
J. C. Nixon ◽  
S. H. Zbarsky

A study was made of the effect of several transplantable tumors on the incorporation in vivo of formate-C14 and tritiated thymidine into the nucleic acids of the host tissues. The presence of the ascitic or subcutaneous forms of the Ehrlich tumor in mice was found to have little effect on the incorporation of formate-C14 into the nucleic acid purines and thymine of the host liver, spleen, kidney, and lung. Experiments with thymidine-H3 were carried out with mice bearing the Erhlich ascites tumor, using three dose levels of the precursor, 0.014, 0.14 and 1.40 μmoles per mouse. At all levels incorporation into liver DNA of the tumor-bearing mice was greater than in controls, whereas the reverse was true for intestinal mucosa, especially at the lowest dosage. With the higher levels of thymidine-H3, incorporation into the DNA of spleen of the tumor animals was higher than in the controls. Variable results were observed for the other tissues examined. The presence of Novikoff hepatoma in rats had little effect on the uptake of tritiated thymidine by the DNA of the host tissues. The presence of the intramuscular form of Walker carcinosarcoma 256 was accompanied by an increased uptake into the DNA of lung and particularly into the DNA of liver and spleen.


1963 ◽  
Vol 41 (1) ◽  
pp. 2237-2247
Author(s):  
J. C. Nixon ◽  
S. H. Zbarsky

A study was made of the effect of several transplantable tumors on the incorporation in vivo of formate-C14 and tritiated thymidine into the nucleic acids of the host tissues. The presence of the ascitic or subcutaneous forms of the Ehrlich tumor in mice was found to have little effect on the incorporation of formate-C14 into the nucleic acid purines and thymine of the host liver, spleen, kidney, and lung. Experiments with thymidine-H3 were carried out with mice bearing the Erhlich ascites tumor, using three dose levels of the precursor, 0.014, 0.14 and 1.40 μmoles per mouse. At all levels incorporation into liver DNA of the tumor-bearing mice was greater than in controls, whereas the reverse was true for intestinal mucosa, especially at the lowest dosage. With the higher levels of thymidine-H3, incorporation into the DNA of spleen of the tumor animals was higher than in the controls. Variable results were observed for the other tissues examined. The presence of Novikoff hepatoma in rats had little effect on the uptake of tritiated thymidine by the DNA of the host tissues. The presence of the intramuscular form of Walker carcinosarcoma 256 was accompanied by an increased uptake into the DNA of lung and particularly into the DNA of liver and spleen.


2018 ◽  
Vol 6 (44) ◽  
pp. 7197-7203 ◽  
Author(s):  
Cory D. Sago ◽  
Sujay Kalathoor ◽  
Jordan P. Fitzgerald ◽  
Gwyneth N. Lando ◽  
Naima Djeddar ◽  
...  

The efficacy of nucleic acid therapies can be limited by unwanted degradation.


Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4659 ◽  
Author(s):  
Steven Ochoa ◽  
Valeria T. Milam

In the last three decades, oligonucleotides have been extensively investigated as probes, molecular ligands and even catalysts within therapeutic and diagnostic applications. The narrow chemical repertoire of natural nucleic acids, however, imposes restrictions on the functional scope of oligonucleotides. Initial efforts to overcome this deficiency in chemical diversity included conservative modifications to the sugar-phosphate backbone or the pendant base groups and resulted in enhanced in vivo performance. More importantly, later work involving other modifications led to the realization of new functional characteristics beyond initial intended therapeutic and diagnostic prospects. These results have inspired the exploration of increasingly exotic chemistries highly divergent from the canonical nucleic acid chemical structure that possess unnatural physiochemical properties. In this review, the authors highlight recent developments in modified oligonucleotides and the thrust towards designing novel nucleic acid-based ligands and catalysts with specifically engineered functions inaccessible to natural oligonucleotides.


1984 ◽  
Vol 17 (1) ◽  
pp. 1-44 ◽  
Author(s):  
John E. Hearst ◽  
Stephen T. Isaacs ◽  
David Kanne ◽  
Henry Rapoport ◽  
Kenneth Straub

Psoralen photochemistry is specific for nucleic acids and is better understood at the molecular level than are all other methods of chemical modification of nucleic acids. These compounds are used both for in vivo structure analysis and for photochemotherapy since they easily penetrate both cells and virus particles. Apparently, natural selection has selected for membrane and virus penetrability during the evolution of these natural products. Most cells are unaffected by relatively high concentrations of psoralens in the absence of ultraviolet light, and the metabolites of the psoralens have thus far not created a problem. Finally, psoralens form both monoadduct and cross-links in nucleic acid helices, the yield of each being easily controlled by the conditions used during the photochemistry.


2006 ◽  
Vol 71 (7) ◽  
pp. 929-955 ◽  
Author(s):  
Vladimir A. Efimov ◽  
Oksana G. Chakhmakhcheva

With the aim to improve physicochemical and biological properties of natural oligonucleotides, many types of DNA analogues and mimics are designed on the basis of hydroxyproline and its derivatives, and their properties are evaluated. Among them, two types of DNA mimics representing hetero-oligomers constructed from alternating monomers of phosphono peptide nucleic acids and monomers on the base of trans-1-acetyl-4-hydroxy-L-proline (HypNA-pPNAs) and oligomers constructed from monomers containing (2S,4R)-1-acetyl-4-hydroxypyrrolidine-2-phosphonic acid backbone (pHypNAs) are of particular interest. In a set of in vitro and in vivo assays, it was shown that HypNA-pPNAs and pHypNAs demonstrated a high potential for the use in nucleic acid based diagnostics, isolation of nucleic acids and antisense experiments. A review with 53 references.


2020 ◽  
Vol 21 (6) ◽  
pp. 2001
Author(s):  
Silvia Mercurio ◽  
Silvia Cauteruccio ◽  
Raoul Manenti ◽  
Simona Candiani ◽  
Giorgio Scarì ◽  
...  

The microRNAs are small RNAs that regulate gene expression at the post-transcriptional level and can be involved in the onset of neurodegenerative diseases and cancer. They are emerging as possible targets for antisense-based therapy, even though the in vivo stability of miRNA analogues is still questioned. We tested the ability of peptide nucleic acids, a novel class of nucleic acid mimics, to downregulate miR-9 in vivo in an invertebrate model organism, the ascidian Ciona intestinalis, by microinjection of antisense molecules in the eggs. It is known that miR-9 is a well-conserved microRNA in bilaterians and we found that it is expressed in epidermal sensory neurons of the tail in the larva of C. intestinalis. Larvae developed from injected eggs showed a reduced differentiation of tail neurons, confirming the possibility to use peptide nucleic acid PNA to downregulate miRNA in a whole organism. By identifying putative targets of miR-9, we discuss the role of this miRNA in the development of the peripheral nervous system of ascidians.


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