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A comparative study of polyconidin effects in the replicative and transcription activity of hepatocyte DNA in intact animals, and on peculiarities of spatial organization DNA in the DNA complex with oligomer-25 conidin was carried out. It was shown that polyconidin binding to DNA results in "cross-linking". This process is accompanied by formation of liquid-crystalline dispersion without abnormal optical activity. Liquid crystals possess high density packing of DNA molecules complexed with quaternary ammonium salt of oligomer-25 conidin. The addition of heparin to liquid-crystalline dispersions or phases, destroys the structure of the DNA complex with quaternary ammonium salt of oligomer-25 conidin. As a result "free" DNA molecules appear, they form the cholesteric liquid-crystalline phase. An increase in transcription activity and synchronization of DNA synthesis in hepatocyte was demonstrated. A correlation between chromatin modification and biological activity of chromatin after formation of the DNA--oligomer-25 conidin complex is proposed.

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In experiments in vivo and in vitro the authors studied antioxidative properties of 4-methyluracil and carnosine, their capacity to inhibit sex and accelerate healing of skin wounds. 4-methyluracil and carnosine discover almost the same capacity to decrease in the tissues of the wound and the blood serum in the formation of various intermediate products of free radical oxidation. Data are given on the study of the dynamics of wound healing after a 5-day treatment with equimolar quantities.

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Effect of 4-methyl uracil on dynamics of morphological patterns and the rate of nucleic acids synthesis was studied in granulation tissue developed during healing of full-layer skin wounds. Application of ointment containing 4-methyl uracil onto the wounds exhibited an antiinflammatory efficiency and decreased accumulation of leukocytes in the wound. The drug shortened the mitotic cycle in dividing fibroblasts, as a result of which periods of DNA synthesis became more frequent exhibiting two days duration. The rate of RNA synthesis was increased 1.5-2-fold. Content of acid glycosaminoglycans and collagen was increased in intercellular space surrounding fibroblasts.

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Dynamics of distribution in subcellular organelles as well as effects on DNA synthesis of heparin, polycanidine (ChAS oligomer of 25 canidine) and their complexes were studied in regenerating rat liver tissue after partial hepatectomy. Polycanidine and heparin penetrated from circulation into hepatocyte cells, nuclei and mitochondria. After consecutive administration of polyelectrolytes polycanidine increased 2-2.5-fold the amount of heparin entering into cells. Polycanidine formed stable complexes with DNP in nuclei. Heparin and its complexes with polycanidine decreased the DNA synthesis within first day. Heparin appears to be responsible for the inhibitory effect, whereas administration of polycanidine only into animals caused a slight increase in 3H-thymidine incorporation into DNA as compared with controls.

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Dynamics of nucleic acid synthesis was studied in granulation tissue, harvested within 2-11 days after an injury of rats with full-layer skin wounds, simultaneously with evaluation of the morphometric patterns of the tissue. Synthesis of nuclear DNA exhibited a wave-shaped dynamics. The intervals between the maximal values of the DNA synthesis constituted 3 days. Within the early steps of wound healing the intensive incorporation of 3H-thymidine into mitochondrial DNA was found, which appears to occur due to active mitochondriogenesis. In dynamics of total and nuclear RNA contents two peaks were observed, which did not coincide in time, thus suggesting the wave-shaped increase in biosynthetic processes in cells.

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Localization of 14C-conidine oligomer (the synthetic antagonist of heparin) and of polyelectrolyte complex heparin-conidine oligomer 25 was studied in cells of regenerating liver tissue within 20 hrs after partial hepatectomy in rats. Effects of heparin, conidine oligomer 25 and of their polyelectrolyte complex on synthesis of nucleic acids were studied. Conidine oligomer 25 penetrated from circulation into hepatocytes and subcellular organelles of regenerating liver cells and was localized mainly in cytosol (75-88%). In nuclei and mitochondria of the hepatocytes 14C-conidine oligomer 25 was mostly found in the fraction of low density of the organelles. Polyanion heparin, polycation conidine oligomer 25 and their polymeric complex impaired replication and transcription processes.

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Distinct activation of thymidine kinase (exceeding 2-3-fold the control values) as well as of nucleoside phosphotransferase (about 50% higher as compared with controls) was observed in blood serum of rats within 24 hrs after partial hepatectomy. Within 48 hrs after beginning of the tissue regeneration the activities of both these enzymes were decreased 1.5-fold; the values normalized within 72 hrs. These enzymatic activities were detected in blood of the patients with impairments of liver, kidney and some other tissues.

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Dynamics of 3H-thymidine incorporation into nuclear DNA and activity of nuclear ribonucleotide reductase were studied within 2 days after partial hepatectomy. The curves describing dynamics of DNA synthesis and the activity of ribonucleotide reductase were of wave-shaped pattern. Maximal enzymatic activity was reached 2 hrs before the nuclear DNA synthesis maximum. An inhibitor of ribonucleotide reductase was found in the globulin fraction of intact liver nuclei; after addition of the inhibitor the activity of the enzyme was decreased 4-5-fold, if the ratio of protein in preparations inhibitor/enzyme was as high as 1:40.

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After a single intravenous administration of sturines A and B into rats subjected to partial hepatectomy, during the periods, corresponding to maximal synthesis of DNA, incorporation of 3H-thymidine into nuclear DNA was decreased by 20-30% and incorporation into mitochondrial DNA--by 40-50%, as compared with control. The treatment with sturines led to distinct decrease in activity of nuclear thymidine kinase and ribonucleotide reductase but did not affect the enzymatic activity in mitochondria. The sturine preparations (at concentrations 10(-6)--10(-3) M) inhibited the activity of these enzymes (of both nuclear and mitochondrial origin) in vitro.

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