Biopolym. Cell. 1986; 2(6):323-327.
Cell Biology
Interaction of alkylating oligonucleotide derivatives with mouse fibroblasts
1Vlassov V. V., 2Gorokhova O. E., 1Ivanova E. M., 1Kutyavin I. V., 1Yurchenko L. V., 1Yakubov L. A., 1, 2Abdukayumov M. N., 1Skoblov Yu. S.
  1. Institute of Bioorganic Chemistry, Siberian Branch of the Academy of Sciences of the USSR
    Novosibirsk, USSR
  2. Experimental Unit, Institute of Nuclear Physics, Academy of Sciences of the Uzbek SSR
    Tashkent, USSR

Abstract

Interaction of 32P labelled oligonucleotides and alkylating oligonucleotide derivatives carrying aromatic 2-chloroethylamine residues with mouse fibroblasts L929 has been investigated. At high concentrations of oligonucleotide derivatives in the culture medium, their uptake by the cells can be ascribed to pinocytosis. At low concentrations (less than 2μM) the efficiency of the uptake is much higher, in particular in the case of the derivatives carrying 2-chloroethylamino groups, most probably due to their absorption on the cells. The binding kinetics plateaus are given 2 hours after incubation at 37 °C. Alkylating oligonucleotide derivatives taken up by the cells efficiency modify cellular biopolymers and remain undegraded in cells 3 hours after incubation at 37 °C. The derivatives show no cytotoxic action at the concentrations used.

References

[1] Grineva NI. Chemical alkylation of specific complexes as a method of infestigation of structure and function of nucleic acids and nucleoproteins. Biokhimiia. 1977; 42(2):370-4.
[2] Knorre DG, Vlasov VV. Oligonucleotides and their derivatives as biologically active ingredients. Vestn Akad Nauk SSSR. 1983; (12):74-81.
[3] Summerton J. Intracellular inactivation of specific nucleotide sequences: a general approach to the treatment of viral diseases and virally-mediated cancers. J Theor Biol. 1979;78(1):77-99.
[4] Vlasov VV, Gorn VV, Kutyavin IV, Yurchenko LV, Sharova NK, Bukrinskaya AF. Possibility of blocking influenza infection by alkylated oligonucleotide derivatives. Mol Gen Mikrobiol Virusol. 1984; 11:36-41.
[5] Vlasov VV, Godovikov AA, Zarytova VF, Ivanova EM, Knorre DG. Suppression of immunoglobulin synthesis in myeloma MORS 21 cells by an alkylating oligonucleotide derivative complementary to the mRNA coding for light-chain immunoglobulin. Dokl Akad Nauk SSSR. 1984;276(5):1263-5.
[6] Ivanova EM, Karpova GG, Knorre DG, Popova VS, Rait AS. Selective modification of polyadenyl fragments of mRNA from Krebs-2 ascites carcinoma cells by an alkylating derivative of nonathymidilyluridine. Mol Biol (Mosk). 1984;18(3):613-9.
[7] Gorn VV, Zarytova VF, Yarmolinskaya EV. Semi-automated solid phase phosphotriester synthesis of oligodeoxyribonucleotides via activation of P-component on the support. Russian Journal of Bioorganic Chemistry. 1983, 9(11):1511-1517.
[8] Mishenina GF, Samukov VV, Shubina TN. Selective modification of monosubstituted phosphate groups in nucleoside and oligonucleotide 5'-mono- and polyphosphates. Russian Journal of Bioorganic Chemistry. 1979, 5 (6):886-894.
[9] Zwerner RK, Wise KS, Action RT. Harvesting the products of cell growth. Methods Enzymol. 1979;58:221-9.
[10] Shick VV, Belyavsky AV, Bavykin SG, Mirzabekov AD. Primary organization of the nucleosome core particles. Sequential arrangement of histones along DNA. J Mol Biol. 1980;139(3):491-517.
[11] Roberts AV, Williams KE, Lloyd JB. The pinocytosis of 125I-labelled poly(vinylpyrrolidone), [14C]sucrose and colloidal [198Au]gold by rat yolk sac cultured in vitro. Biochem J. 1977;168(2):239-44.