ISC, CAS, Google Scholar     h-index: 20

Document Type : Original Research Article

Authors

Belarusian State University, ISEI BSU, Minsk, Belarus

10.33945/SAMI/PCBR.2019.4.3

Abstract

The influence of the modified nucleotide arabinofuranosylcytosine-5`-monophosphate in the form of the free acid (Ara-CMP) and its salts with emoxipin (Ara-CMP+Em) on the viability of peripheral blood mononuclear cells, the lymphocyte proliferation of mitogen-stimulated cells was studied. It was shown that emoxipin - the compound with strong antioxidant properties - does not lead to inhibition of the main function of the antimetabolite Ara-CMP, namely, cell growth arrest (p = 0.96) and lysis of target cells (p = 0.97). Under the conditions of nonspecific stimulation of lymphocytes, Ara-CMP at high concentrations (10-4 M) increased in both IFNγ-secreting T-lymphocytes (five times) and IFNγ-secreting other lymphocytes (three times). Emoxipin led to almost complete leveling of the detected effect.

Graphical Abstract

Influence of arabinofuranosylcytosine-5`-monophosphate and its emoxipin salt on viability and functional status of peripheral blood lymphocytes subpopulations

Keywords

Main Subjects

References:    
 
[1] F. Cividini, R. Pesi, L. Chaloin, S. Allegrini, M. Camici, E. Cros-Perrial, C. Dumontet, L.P. Jordheim and M.G. Tozzi, The purine analog fludarabine acts as a cytosolic 5′-nucleotidase II inhibitor. Biochemical pharmacology,  94 (2015)  63-68.
[2] C. Harrington and F.W. Perrino, The effects of cytosine arabinoside on RNA-primed DNA synthesis by DNA polymerase α-primase. Journal of Biological Chemistry,  270 (1995)  26664-26669.
[3] T. Mikita and G.P. Beardsley, Functional consequences of the arabinosylcytosine structural lesion in DNA. Biochemistry,  27 (1988)  4698-4705.
[4] F. Perrino and H. Mekosh, Incorporation of cytosine arabinoside monophosphate into DNA at internucleotide linkages by human DNA polymerase alpha. Journal of Biological Chemistry,  267 (1992)  23043-23051.
[5] M. Tsuda, K. Terada, M. Ooka, K. Kobayashi, H. Sasanuma, R. Fujisawa, T. Tsurimoto, J. Yamamoto, S. Iwai and K. Kadoda, The dominant role of proofreading exonuclease activity of replicative polymerase ε in cellular tolerance to cytarabine (Ara-C). Oncotarget,  8 (2017)  33457.
[6] P.A. Dijkwel and F. Wanka, Enhanced release of nascent single strands from DNA synthesized in the presence of arabinosylcytosine. Biochimica et Biophysica Acta (BBA)-Nucleic Acids and Protein Synthesis,  520 (1978)  461-471.
[7] D.D. Ross, S.-R.S. Chen and D.P. Cuddy, Effects of 1-β-d-Arabinofuranosylcytosine in DNA Replication Intermediates Monitored by pH-Step Alkaline Elution. Cancer research,  50 (1990)  2658-2666.
[8] P. Huang, S. Chubb and W. Plunkett, Termination of DNA synthesis by 9-beta-D-arabinofuranosyl-2-fluoroadenine. A mechanism for cytotoxicity. Journal of Biological Chemistry,  265 (1990)  16617-16625.
[9] N. Tsesmetzis, C.B. Paulin, S.G. Rudd and N. Herold, Nucleobase and nucleoside analogues: resistance and re-sensitisation at the level of pharmacokinetics, pharmacodynamics and metabolism. Cancers,  10 (2018)  240.
[10] K.I. Block, A.C. Koch, M.N. Mead, P.K. Tothy, R.A. Newman and C. Gyllenhaal, Impact of antioxidant supplementation on chemotherapeutic toxicity: a systematic review of the evidence from randomized controlled trials. International journal of cancer,  123 (2008)  1227-1239.
[11] H. Pan, P. Mukhopadhyay, M. Rajesh, V. Patel, B. Mukhopadhyay, B. Gao, G. Haskó and P. Pacher, Cannabidiol attenuates cisplatin-induced nephrotoxicity by decreasing oxidative/nitrosative stress, inflammation, and cell death. Journal of Pharmacology and Experimental Therapeutics,  328 (2009)  708-714.
[12] A. babaei and A. Taheri, Direct Electrochemistry and Electrocatalysis of Myoglobin Immobilized on a Novel Chitosan-Nickel Hydroxide Nanoparticles-Carbon Nanotubes Biocomposite Modified Glassy Carbon Electrode. Anal. Bioanal. Electrochem.,  4 (2012)  342 - 356.
[13] R. Jalilian and A. Taheri, Synthesis and application of a novel core-shell-shell magnetic ion imprinted polymer as a selective adsorbent of trace amounts of silver ions. e-Polymers,  18 (2018)  123-134.
[14] V.K. Shitikov, V.A. Terekhova, B. A. Uzbekov, K.A. Kydralieva and B.M. Khudaybergenov, Principles of ecology,  4(3) (2015)  73 (in Russian).
[15] V.S. Yu, Journal of Siberian Medical Sciences,  2 (2013)  1 (in Russian).
[16] A. Agita and M.T. Alsagaff, Inflammation, immunity, and hypertension. Acta Med Indones,  49 (2017)  158-165.