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Internalization of exogenous DNA into internal compartments of murine bone marrow cells

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Russian Journal of Genetics: Applied Research

Abstract

Injections of exogenous DNA combined with a cytostatic agent cyclophosphamide (CP) cause illness and death in experimental mice. This phenomenon is referred to as delayed death. It has been found that fragments of exogenous DNA reach the bone marrow and enter the bone marrow cells (BMCs) 1–5 min after injections. Fragments of exogenous DNA are captured from culture medium by BMCs generated ex vivo. After joint incubation with BMCs of mice, the fragments of exogenous DNA are internalized into internal compartments in a nondegraded form. Up to 1800 kb of nucleic acid material can be present in each cell of BMCs generated ex vivo and treated with fragments of exogenous DNA. The fragments of exogenous DNA internalized in BMCs generated ex vivo of both intact and CP pretreated mice become circularized. In the case of intact mice, the fragments of exogenous DNA can form high-molecular weight structures in vivo. It is suggested that the exogenous fragments localized in BMC nuclei integrate into chromosome(s) of the recipient mouse genome when treated with CP and exogenous DNA.

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References

  • Abrams, R.A., McCormack, K., Bowles, C., and Deisseroth, A.B., Cyclephosphamide Treatment Expands the Circulating Hematopoietic Stem Cell Pool in Dogs, J. Clin. Invest., 1981, vol. 67, no. 5, pp. 1392–1399.

    Article  PubMed  CAS  Google Scholar 

  • Alyamkina, E.A., Likhacheva, A.S., Nikolin, V.P., et al., The Effect of Exogenous DNA Associated with Protamine on the Growth of Experimental Mouse Tumors, Vopr. Onkol., 2009, vol. 55, no. 6, pp. 765–768.

    CAS  Google Scholar 

  • Bhagwat, N., Olsen, A.L., Wang, A.T., et al., SPF-ERCCI Participates in the Fanconi Anemia Pathway of Cross-Link Repair, Mol. Cell. Biol., 2009, vol. 29, no. 24, pp. 6427–6437.

    Article  PubMed  CAS  Google Scholar 

  • Derbyshire, M.K., Epstein, L.H., Young, C.S.H., et al., Nonhomologous Recombination in Human Cells, Mol. Cell Biol., 1994, vol. 14, no. 1, pp. 156–169.

    PubMed  CAS  Google Scholar 

  • Dolgova, E.V., Likhacheva, A.S., Orishchenko, K.E., et al., Interstrand Cross-Link Repair in DNA Molecule, Inform. Vestnik VOGiS, 2010, vol. 14, no. 2, pp. 332–356.

    Google Scholar 

  • Dolgova, E.V., Nikolin, V.P., Popova, N.A., et al., Pathological Changes That Occur in Mice Treated with a Combination of Cyclophosphamide and Exogenous DNA (in press).

  • Dolgova, E.V., Proskurina, A.S., Nikolin, V.P., et al., Characteristics of Temporal Parameters of Manifestation of the Toxic Effect of Exogenous DNA Injection after Pretreatment with the Cytostatic Cyclophosphamide, Inform. Vestnik VOGiS, 2011, vol. 15, no. 4, pp. 485–492.

    Google Scholar 

  • Dolgova, E.V., Rogachev, V.A., Nikolin, V.P., et al., Leukostimulatory Effect of Exogenous DNA Fragments Protected with Protamine in Cyclophosphamide-Induced Myelosuppression in Mice, Vopr. Onkol., 2009, vol. 55, no. 6, pp. 761–764.

    PubMed  CAS  Google Scholar 

  • Durant, S.T., et al., The SET Domain Protein Metnase Mediates Foreign DNA Integration and Links Integration to Nonhomologous End-Joining Repair, Proc. Natl. Acad. Sci. USA, 2005, vol. 102, no. 50, pp. 18075–18080.

    Article  PubMed  Google Scholar 

  • Filaci, G., Gerloni, M., Rizzi, M., et al., Spontaneous Transgenesis of Human B Lymphocytes, Gene Ther., 2004, no. 1, pp. 42–51.

  • Fleming, R.A., An Overview of Cyclophosphamide and Ifosfamide Pharmacology, Pharmacotherapy, 1997, vol. 17, pp. 146–154.

    Google Scholar 

  • Fleming, R.A., An Overview of Cyclophosphamide and Ifosfamide Pharmacology, Pharmacotherapy, 1997, vol. 17, pp. 146–154.

    Google Scholar 

  • Gosden, J. and Lawson, D., In situ Cyclic Amplification of Oligonucleotide Primed Synthesis (Cycling PRINS), in PCR Application Manual, Mannheim, Germany: Boehringer Mannheim Corp., 1995, pp. 115–118.

    Google Scholar 

  • Hashzume, T. and Shimizu, N., Dissection of Mammalian Replicators by a Novel Plasmid Stability Assay, J. Cell Biochem., 2007, vol. 101, no. 3, pp. 552–565.

    Article  Google Scholar 

  • Helleday, T., Pathways for Mitotic Homologous Recombination in Mammalian Cells, Mutat. Res., 2003, nos. 1/2, pp. 103–115.

  • Lees-Miller, S.P. and Meek, K., Repair of DNA Double Strand Breaks by Non-Homologous End Joining, Biochimie, 2003, vol. 85, no. 11, pp. 1161–1173.

    Article  PubMed  CAS  Google Scholar 

  • Likhacheva, A.S., Rogachev, V.A., Nikolin, V.P., et al., Participation of Exogenous DNA in the Molecular Processes That Occur in Somatic Cells, Inform. Vestnik VOGiS, 2008, vol. 12, no. 3, pp. 426–473.

    Google Scholar 

  • Likhacheva, A.S., Nikolin, V.P., Popova, N.A., et al., Exogenous DNA Can Be Captured by Stem Cells and Be Involved in Their Rescue from Death after Lethal-Dose γ-Radiation, Gene Ther. Mol. Biol., 2007, vol. 11, pp. 305–314.

    Google Scholar 

  • Lin, F.L., Sperle, K., and Sternberg, N., Recombination in Mouse I. Cells between DNA Introduced into Cells and Homologous Chromosomal Sequences, Proc. Natl. Acad. Sci. USA, 1985, vol. 82, no. 5, pp. 1391–1395.

    Article  PubMed  CAS  Google Scholar 

  • Mazur, L. and Czyzewska, A., Immunocytochemical Analysis of Apoptotic Bone Marrow Cells after Treatment of Mice with WR-2721 and Chemotherapeutic Drugs, Folia Histochem. Cytobiol., 2001, vol. 39, no. 2, pp. 63–66.

    PubMed  CAS  Google Scholar 

  • Murata, S., Takasaki, N., Saiton, M., and Okada, N., Determination of the Phylogenetic Relationships among Pacific Salmonids by Using Short Interspersed Elements (SINEs) as Temporal Landmarks of Evolution, Proc. Natl. Acad. Sci. USA, 1993, vol. 90, pp. 6995–6999.

    Article  PubMed  CAS  Google Scholar 

  • Niedernhofer, L.J., Odijk, H., Budzowska, M., et al., The Structure-Specific Endonuclease Erccl-Xpfis Required to Resolve DNA Interstrand Cross-Link-Induced Double-Strand Breaks, Mol. Cell. Biol., 2004, vol. 24, no. 13, pp. 5776–5787.

    Article  PubMed  CAS  Google Scholar 

  • Pinkel, D., Straume, T., and Gray, J.W., Cytogenetic Analysis using Quantitative, High-Sensitivity, Fluorescence Hybridization, Proc. Natl. Acad. Sci. USA, 1986, vol. 83, no. 9, pp. 2934–2938.

    Article  PubMed  CAS  Google Scholar 

  • Raynard, S., Niu, H., and Sung, P., DNA Double-Strand Break Processing: the Beginning of the End, Genes Dev., 2008, vol. 22, no. 21, pp. 2903–2907.

    Article  PubMed  CAS  Google Scholar 

  • Roberts, D.B., Drosophila: A Practical Approach, Roberts, D.B., Ed., Oxford: IRL Press, 1986.

    Google Scholar 

  • Saleh-Gohari, N., Bryant, H.E., Schultz, N., et al., Spontaneous Homologous Recombination Is Induced by Collapsed Replication Forks That Are Caused by Endogenous DNA Single-Strand Breaks, Mol. Cell. Biol., 2005, vol. 25, no. 16, pp. 7158–7169.

    Article  PubMed  CAS  Google Scholar 

  • Salem, M.L., El-Naggar, S.A., and Cole, D.J., Cyclophosphamide Induces Bone Marrow to Yield Higher Numbers of Precursor Dendritic Cells in vitro Capable of Functional Antigen Presentation to T Cells in vivo, Vell. Immunol., 2010, vol. 261, no. 2, pp. 134–143.

    Article  CAS  Google Scholar 

  • Sambrook, J., Fritisch, E.F., and Maniatis, T., Molecular Cloning. A Laboratory Manual, 2nd ed., Cold Spring Harbor: Cold Spring Harbor Lab. Press, 1989.

    Google Scholar 

  • De Silva, I.U., McHugh, P.J., Clingen, P.H., and Hartley, J.A., Defining the Roles of Nucleotide Excision Repair and Recombination in the Repair of DNA Interstrand Cross-Links in Mammalian Cells, Mol. Cell. Biol., 2000, vol. 20, no. 21, pp. 7980–7990.

    Article  PubMed  Google Scholar 

  • Stanyon, R. and Galleni, R., A Rapid Fibroblast Culture Technique for High Resolution Karyotypes, Ital. J. Zool., 1991, vol. 58, no. 1, pp. 81–83.

    Google Scholar 

  • Thomas, K.R., Folger, K.R., and Capecchi, M.R., High Frequency Targeting of Genes to Specific Sites in the Mammalian Genome, Cell, 1986, vol. 44, no. 3, pp. 419–428.

    Article  PubMed  CAS  Google Scholar 

  • Wang, H., Rosidi, B., Perrault, R., et al., DNA Ligase III as a Candidate Component of Backup Pathways of Nonhomologous End Joining, Cancer Res., 2005, vol. 65, no. 10, pp. 4020–4030.

    Article  PubMed  CAS  Google Scholar 

  • Znang, N., Liu, X., Li, L., and Legerski, R., Double-Strand Breaks Induce Homologous Recombinational Repair of Interstrand Cross-Links via Cooperation of MSH2, ERCC1-XPF, REV3, and the Fanconi Anemia Pathway, DNA Repair, 2007, vol. 6, no. 11, pp. 1670–1678.

    Article  Google Scholar 

  • Zou, L., Singe- and Double-Stranded DNA: Building a Trigger of ATR-Mediated DNA Damage Response, Genes Dev., 2007, vol. 21, no. 8, pp. 879–885.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia

    E. V. Dolgova, V. P. Nikolin, N. A. Popova, A. S. Proskurina, K. E. Orishenko, E. A. Alyamkina, Y. R. Efremov, V. A. Rogachev & S. S. Bogachev

  2. Institute of Clinical Immunology, Siberian Branch, Russian Academy of Medical Sciences, Novosibirsk, Russia

    E. R. Chernykh & A. A. Ostanin

  3. State Research Center of Virology and Biotechnology Vector, Novosibirsk, Russia

    E. M. Malkova & O. S. Taranov

  4. City Clinical Hospital No. 1, Novosibirsk, Russia

    S. V. Sidorov

  5. TOO Panagen, Novosibirsk, Russia

    M. A. Shurdov

Authors
  1. E. V. Dolgova
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  2. V. P. Nikolin
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  3. N. A. Popova
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  4. A. S. Proskurina
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  5. K. E. Orishenko
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  6. E. A. Alyamkina
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  7. Y. R. Efremov
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  8. E. R. Chernykh
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  9. A. A. Ostanin
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  10. E. M. Malkova
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  11. O. S. Taranov
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  12. V. A. Rogachev
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  13. S. V. Sidorov
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  14. S. S. Bogachev
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  15. M. A. Shurdov
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Corresponding author

Correspondence to E. V. Dolgova.

Additional information

Original Russian Text © E.V. Dolgova, V.P. Nikolin, N.A. Popova, A.S. Proskurina, K.E. Orishenko, E.A. Alyamkina, Y.R. Efremov, E.R. Chernykh, A.A. Ostanin, E.M. Malkova, O.S. Taranov, V.A. Rogachev, S.V. Sidorov, S.S. Bogachev, M.A. Shurdov, 2012, published in Vavilovskii Zhurnal Genetiki i Selektsii, 2012, Vol. 16, No. 2, pp. 397–414.

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Dolgova, E.V., Nikolin, V.P., Popova, N.A. et al. Internalization of exogenous DNA into internal compartments of murine bone marrow cells. Russ J Genet Appl Res 2, 440–452 (2012). https://doi.org/10.1134/S2079059712060056

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  • DOI: https://doi.org/10.1134/S2079059712060056

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