Biopolym. Cell. 2004; 20(4):343-346.
Molecular Biomedicine
Research of antitumor ctivity of thioTEPA alkylated nucleic acid and nucleotides in vivo
1Voloshchuk T. P., 1Patskovskii Yu. V., 1Potopalskii A. I., 1Vorobyeva I. I.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680

Abstract

The antitumor activity of the thioTEPA alkylated DNA preparations of various origin (cattle spleen, salmon sperm, chicken erythrocytes), yeast RNA and mononucleotides - ATP and GTP has been established in the experiments in vivo on mice with interweave Ehrlich carcinoma. The therapeutic doses (100–300 mg/kg of the weight) of these preparations insured the tumor growth inhibition by 90–100 % at the toxic dose LD50 between 1.5 and 2 g/kg. The DNA preparations, modified by monofunctional alkylating agents (ethylenimine and monoaziridinediethylphosphate), have no noticeable antitumor effect.

References

[1] Voloshchuk TP, Patskovskii IuV, Potopal'skii AI. Alkylation of nucleic acid components by ethyleneimine derivatives. I. Alkylation of bases. Bioorg Khim. 1990;16(7):981-90.
[2] Voloshchuk TP, Patskovskii YuV, Potopalskii AI, Vorobyeva II. Effect of thioTEPA modified DNA forms and their monomeric components of varying alkylation degree on synthesis of nucleic acids in tumor cells. Biopolym Cell. 2003; 19(6):513-9.
[3] Lidak MSh, Giller SA, Medne AYa. The synthesis of Thiotepa. TioTEFA. Riga: Izd-vo AN Latv. SSR. 1961; 5-8.
[4] Grechkin NP. Organophosphorus derivatives of ethyleneimine. Posts. 1. Interaction ethyleneimine with chlorides dialkylphosphorous acids. Izv. AN SSSR. Ser. Khim. 1956; 5:538-43.
[5] Voloshchuk TP, Patskovskiy YuV, Potopal'skiy AI. Alkylation of nucleic acid components with ethylenimine and its derivatives. 3. Alkylation of nucleotides Bioorg Khim. 1993; 19(5):562-9.
[6] Voloshchuk TP, Patskovskiy YuV, Potopal'skii AI. Alkylation of nucleic acid components with ethylenimine and its derivatives. IV. Alkylation of homopolynucleotides and DNA. Bioorg Khim. 1999;25(6):464-73.
[7] Zhdanov GL. Methods for studying compounds with antitumor action alleged. Models and methods of experimental oncology. Moscow, 1960; 201-243.
[8] Loke SL, Stein CA, Zhang XH, Mori K, Nakanishi M, Subasinghe C, Cohen JS, Neckers LM. Characterization of oligonucleotide transport into living cells. Proc Natl Acad Sci U S A. 1989;86(10):3474-8.