Biopolym. Cell. 1996; 12(1):75-85.
Antiadenovirus and immunostimulating actions of 6-azacylidine
1Nosach L. N., 1Dyachenko N. S., 2Shalamay A. S., 2Alekseeva I. V., 3Kushko L. Ya., 3Ozvinchuk I. I., 1Zhovnovataya V. L., 1Butenko S. L., 3Petrovskaya I. A., 3Drannik G. N.
  1. D. K. Zabolotny Institute of Microbiology and Virology, NAS of Ukraine
    154, Academika Zabolotnogo Str., Kyiv, Ukraine, 03680
  2. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  3. Institute of Urology and Nephrology AMS of Ukraine
    9-a, Yu. Kotsubyns'koho Str., Kyiv, Ukraine, 04053

Abstract

The influence of an original cytidine analogue, 6-azacytidine (6-AC), on the reproduction of a human type I adenovirus in HeLa cell cultures, on a synthesis of nucleic acids aswellasonsome characteristics showing the state of the cell culture monolayer and functional activity of various populations of immunocompetent cells in vitro has been studied. It was established that the 6-AC effectively inhibits the adenovirus reproduction in a wide concentration range, has a high antiviral index (62), and in vitro conditions it possesses the immunomodulating action stimulating the T-lymphocyte proliferation, phagocytic activity and activity of natural killers. Depending on the concentration, the 6-AC exerts a variable action on a synthesis of nucleic acids, particularly on DNA in the non-infected and infected cells: its high concentrations, which completely or almost completely inhibit the adenovirus reproduction, decrease nucleic acids synthesis; less concentrations stimulate it suppressing adenovirus reproduction for 30 % or less. The 6-AC concentrations differently inhibiting the adenovirus reproduction did not exert the cytodestructive effect on the monolayer cell culture, butthey inhibit its mitotic and growth activities.

References

[1] Yershov FI, Chizhov NP, Tazulakhova ZB. Antiviral agents. St-Peterburg, 1993. 104 p.
[2] A. p. 1625881 A1, USSR. A method of producing 6-azacytidine. A. S. Shalamay, S. S. Ognyanik, I. V. Alekseyeva, V. S. Goncharenko. Discoveries. 1991, 5.
[3] Starcheus AP, ChernetskiД­ VP. Effect of 6-azauridine, 6-azacytidine and 8-azaguanine on reproduction of IV type adenovirus in a tissue culture. Mikrobiol Zh. 1967;29(2):157-60.
[4] Bektemirov TA, Lintskaia GL, Chernetskii VP, Galegov GA. The inhibiting effect of 6-azacytidine on reproduction of smallpox virus in tissue culture. Vopr Med Khim. 1974;20(1):50-1.
[5] Frolov AF, Radolitskaya LS, Reshot'ko LYa, Chernetskiy VP. Action anomalous nucleosides on experimental influenza infection of white mice. Viruses and virus. disease: Resp. sb; Kiyev: Zdorov'ya, 1986;(14):3-6.
[6] Petrusha NA. Anticancer properties of some anomalous nucleosides: Author. Dis. ... PhD. biol. Sciences. Kiev, 1969. 15 p.
[7] Skripal' IG, Babichev VV, Bezugly? SV, Egorov OV, Korobkova ES, Malinovskaia LP, Panchenko LP, Tokovenko IP, Shalama? AS, Alekseeva IV. The inhibitory action of 6-azacytidine on Mollicutes and its proposed mechanism. Mikrobiol Zh. 1993;55(2):99-104.
[8] Nosach LN, Diachenko NS, Zhovnovataya VL et al. Effect of anomalous nucleosides on reproduction and synthesis of I adenovirus viruenth polypeptides. Antiviral agents: Proc. V. Intern. Symposium. soc. countries. Riga, 1982: 151-2.
[9] Nosach LN, Butenko SI, Timofeeva MIa, Diachenko NS, Tikhomirova TP. An analysis of the DNA synthesized in adenovirus-infected cells under exposure to nucleoside analogs. Mikrobiol Zh. 1989;51(6):73-5.
[10] Nosach LN, Diachenko NS, Butenko SI et al. Effect of 6-azacytidine for expression adenoviral genome. New approaches to chemotherapy of viral infections. Riga: Zinatne, 1991: 87-93.
[11] Alekseyeva IV, Sidorov GV, Shalamay AS. et al. Synthesis of tritium-labeled 6-azauridine, and 6-azacytidine. Molecular methods. Biology: Proc. scientific. tr. Kiev, 1986: 52-8.
[12] Nosach LN, Diachenko NS. Cytopathology of adenovirus infection. Kiev: Naukova Dumka, 1982. 124 p.
[13] Andzhaparidze OG, Gavrilov VI, Semenov BF, Stepanova LG. Tissue culture in virology research. M. Medgiz, 1962. 24 p.
[14] Diachenko NS, Nas I, Berenchi D. Adenovirus, a cell organism. Kiev: Naukova Dumka, 1988. 232 p.
[15] Zemskov VM. Immunomodulatory effects of nucleosides and their derivatives. Defects nucleic acid metabolism and immunodeficiencies. Immunologiia. 1990;(3):4-7.
[16] Preobrazhenskaya MN, Mel'nik SYA. Analog components of nucleic acids, nucleic acid metabolism inhibitors. Itogi nauki i tekhniki (Ser. Bioorg. khimiya; vol 1). M.: VINITI, 1984. 244 p.
[17] Petrusha NA. Toxico-pharmacological properties of 6-azacytidine. Farmakol Toksikol. 1987;50(2):75-6.
[18] Galushko SV, Shishkina IP. Reversed-phase ion-paired high-performance liquid chromatographic determination of 6-azacytidine in blood. J Chromatogr. 1985;345(1):157-61.
[19] Landolph JR, Jones PA. Mutagenicity of 5-azacytidine and related nucleosides in C3H/10T 1/2 clone 8 and V79 cells. Cancer Res. 1982;42(3):817-23.