title: Combination of cyclophosphamide and double-stranded DNA demonstrates synergistic toxicity against established xenografts.
abstract: BACKGROUND
  Extracellular double-stranded DNA participates in various processes in an organism. Here we report the suppressive effects of fragmented human double-stranded DNA along or in combination with cyclophosphamide on solid and ascites grafts of mouse Krebs-2 tumor cells and DNA preparation on human breast adenocarcinoma cell line MCF-7.
  
  
  METHODS
  Apoptosis and necrosis were assayed by electrophoretic analysis (DNA nucleosomal fragmentation) and by measurements of LDH levels in ascitic fluid, respectively. DNA internalization into MCF-7 was analyzed by flow cytometry and fluorescence microscopy.
  
  
  RESULTS
  Direct cytotoxic activity of double-stranded DNA (along or in combination with cyclophosphamide) on a solid transplant was demonstrated. This resulted in delayed solid tumor proliferation and partial tumor lysis due to necrosis of the tumor and adjacent tissues. In the case of ascites form of tumor, extensive apoptosis and secondary necrosis were observed. Similarly, MCF-7 cells showed induction of massive apoptosis (up to 45%) as a result of treatments with double-stranded DNA preparation.
  
  
  CONCLUSIONS
  Double-stranded DNA (along or in combination with cyclophosphamide) induces massive apoptosis of Krebs-2 ascite cells and MCF-7 cell line (DNA only). In treated mice it reduces the integrity of gut wall cells and contributes to the development of systemic inflammatory reaction.
authors: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva ave, 630090 Novosibirsk, Russia.
authors: Ekaterina A
authors: EA
authors: Alyamkina
authors: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva ave, 630090 Novosibirsk, Russia.
authors: Valeriy P
authors: VP
authors: Nikolin
authors: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva ave, 630090 Novosibirsk, Russia ; Novosibirsk State University, Novosibirsk, 630090 Russia.
authors: Nelly A
authors: NA
authors: Popova
authors: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva ave, 630090 Novosibirsk, Russia.
authors: Alexandra M
authors: AM
authors: Minkevich
authors: Novosibirsk State University, Novosibirsk, 630090 Russia.
authors: Artem V
authors: AV
authors: Kozel
authors: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva ave, 630090 Novosibirsk, Russia.
authors: Evgenia V
authors: EV
authors: Dolgova
authors: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva ave, 630090 Novosibirsk, Russia ; Novosibirsk State University, Novosibirsk, 630090 Russia.
authors: Yaroslav R
authors: YR
authors: Efremov
authors: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva ave, 630090 Novosibirsk, Russia ; Novosibirsk State University, Novosibirsk, 630090 Russia.
authors: Sergey I
authors: SI
authors: Bayborodin
authors: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva ave, 630090 Novosibirsk, Russia ; Novosibirsk State University, Novosibirsk, 630090 Russia.
authors: Oleg M
authors: OM
authors: Andrushkevich
authors: The State Research Center of Virology and Biotechnology VECTOR, Koltsovo, Novosibirsk region 630559 Russia.
authors: Oleg S
authors: OS
authors: Taranov
authors: The State Research Center of Virology and Biotechnology VECTOR, Koltsovo, Novosibirsk region 630559 Russia.
authors: Vladimir V
authors: VV
authors: Omigov
authors: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva ave, 630090 Novosibirsk, Russia.
authors: Vladimir A
authors: VA
authors: Rogachev
authors: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva ave, 630090 Novosibirsk, Russia.
authors: Anastasia S
authors: AS
authors: Proskurina
authors: Novosibirsk State Medical Academy, Novosibirsk, 630091 Russia.
authors: Evgeniy I
authors: EI
authors: Vereschagin
authors: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva ave, 630090 Novosibirsk, Russia.
authors: Elena V
authors: EV
authors: Kiseleva
authors: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva ave, 630090 Novosibirsk, Russia.
authors: Maria V
authors: MV
authors: Zhukova
authors: Institute of Clinical Immunology, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk, 630099 Russia.
authors: Alexandr A
authors: AA
authors: Ostanin
authors: Institute of Clinical Immunology, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk, 630099 Russia.
authors: Elena R
authors: ER
authors: Chernykh
authors: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva ave, 630090 Novosibirsk, Russia.
authors: Sergey S
authors: SS
authors: Bogachev
authors: LLC Panagen, Gorno-Altaisk, Russia.
authors: Mikhail A
authors: MA
authors: Shurdov
keywords: Apoptosis; Ascites Krebs-2; Cyclophosphamide; Double-stranded DNA; MCF-7; Necrosis; Sepsis