Skip to main content

Advertisement

SpringerLink
Log in

Nucleic acids in circulation: Are they harmful to the host?

  • Review
  • Published:
Journal of Biosciences Aims and scope Submit manuscript

Abstract

It has been estimated that 1011–1012 cells, primarily of haematogenous origin, die in the adult human body daily, and a similar number is regenerated to maintain homeostasis. Despite the presence of an efficient scavenging system for dead cells, considerable amounts of fragmented genetic material enter the circulation in healthy individuals. Elevated blood levels of extracellular nucleic acids have been reported in various disease conditions; such as ageing and age-related degenerative disorders, cancer; acute and chronic inflammatory conditions, severe trauma and autoimmune disorders. In addition to genomic DNA and nucleosomes, mitochondrial DNA is also found in circulation, as are RNA and microRNA. There is extensive literature that suggests that extraneously added nucleic acids have biological actions. They can enter into cells in vitro and in vivo and induce genetic transformation and cellular and chromosomal damage; and experimentally added nucleic acids are capable of activating both innate and adaptive immune systems and inducing a sterile inflammatory response. The possibility as to whether circulating nucleic acids may, likewise, have biological activities has not been explored. In this review we raise the question as to whether circulating nucleic acids may have damaging effects on the host and be implicated in ageing and diverse acute and chronic human pathologies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Anker P and Stroun M 1972 Bacterial ribonucleic acid in the frog brain after a bacterial peritoneal infection. Science 178 621–623

    PubMed  CAS  Google Scholar 

  • Anker P, Lyautey J, Lefort F, Lederrey C and Stroun M 1994 Transformation of NIH/3T3 cells and SW 480 cells displaying K-ras mutation. C. R. Acad. Sci. III 317 869–874

    PubMed  CAS  Google Scholar 

  • Ayad SR and Fox M 1968 DNA uptake by a mutant strain of lymphoma cells. Nature 220 35–38

    PubMed  CAS  Google Scholar 

  • Bandeen-Roche K, Walston JD, Huang Y, Semba RD and Ferrucci L 2009 Measuring systemic inflammatory regulation in older adults: evidence and utility. Rejuvenation Res. 12 403–410

    PubMed  Google Scholar 

  • Barada FA Jr, Suratt PM, Davis JS 4th, Sipes JN, Castle CA, Taylor RP and Godfrey SM 1980 Free plasma DNA in patients with pulmonary embolism. South. Med. J. 73 345–346, 350

    PubMed  Google Scholar 

  • Barton GM, Kagan JC and Medzhitov R 2006 Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA. Nat. Immunol. 7 49–56

    PubMed  CAS  Google Scholar 

  • Bendich A, Wilczok T and Borenfreund E 1965 Circulating DNA as a possible factor in oncogenesis. Science 148 374–376

    PubMed  CAS  Google Scholar 

  • Benoit M, Fenollar F, Raoult D and Mege JL 2007 Increased levels of circulating IL-16 and apoptosis markers are related to the activity of Whipple's disease. PLoS One 2 e494

    PubMed  Google Scholar 

  • Best BP 2009 Nuclear DNA damage as a direct cause of aging. Rejuvenation Res. 12 199–208

    PubMed  CAS  Google Scholar 

  • Bhargava PM and Shanmugam G 1971 Uptake of nonviral nucleic acids by mammalian cells. Prog. Nucleic Acid Res. Mol. Biol. 11 103–192

    PubMed  CAS  Google Scholar 

  • Blasiak J, Arabski M, Krupa R, Wozniak K, Zadrozny M, Kasznicki J, Zurawska M and Drzewoski J 2004 DNA damage and repair in type 2 diabetes mellitus. Mutat. Res. 554 297–304

    PubMed  CAS  Google Scholar 

  • Board RE, Williams VS, Knight L, Shaw J, Greystoke A, Ranson M, Dive C, Blackhall FH, et al. 2008 Isolation and extraction of circulating tumor DNA from patients with small cell lung cancer. Ann. NY Acad. Sci. 1137 98–107

    PubMed  CAS  Google Scholar 

  • Botezatu I, Serdyuk O, Potapova G, Shelepov V, Alechina R, Molyaka Y, Ananév V, Bazin I, et al. 2000 Genetic analysis of DNA excreted in urine: a new approach for detecting specific genomic DNA sequences from cells dying in an organism. Clin. Chem. 46 1078–1084

    PubMed  CAS  Google Scholar 

  • Burkholder GD and Mukherjee BB 1970 Uptake of isolated metaphase chromosomes by mammalian cells in vitro. Exp. Cell Res. 61 413–422

    PubMed  CAS  Google Scholar 

  • Butt AN, Shalchi Z, Hamaoui K, Samadhan A, Powrie J, Smith S, Janikoun S and Swaminathan R 2006 Circulating nucleic acids and diabetic complications. Ann. NY Acad. Sci. 1075 258–270

    PubMed  CAS  Google Scholar 

  • Campisi J and Vijg J 2009 Does damage to DNA and other macromolecules play a role in aging? If so, how? J. Gerontol. A Biol. Sci. Med. Sci. 64 175–178

    PubMed  Google Scholar 

  • Chan KC, Yeung SW, Lui WB, Rainer TH and Lo YM 2005 Effects of preanalytical factors on the molecular size of cell-free DNA in blood. Clin. Chem. 51 781–784

    PubMed  CAS  Google Scholar 

  • Chang CP, Chia RH, Wu TL, Tsao KC, Sun CF and Wu JT 2003 Elevated cell-free serum DNA detected in patients with myocardial infarction. Clin. Chim. Acta 327 95–101

    PubMed  CAS  Google Scholar 

  • Chen GY and Nuñez G 2010 Sterile inflammation: sensing and reacting to damage. Nat. Rev. Immunol. 10 826–837

    PubMed  CAS  Google Scholar 

  • Chiu RW and Lo YM 2004 Recent developments in fetal DNA in maternal plasma. Ann. NY Acad. Sci. 1022 100–104

    PubMed  CAS  Google Scholar 

  • Chiu RW, Chan LY, Lam NY, Tsui NB, Ng EK, Rainer TH and Lo YM 2003 Quantitative analysis of circulating mitochondrial DNA in plasma. Clin. Chem. 49 719–726

    PubMed  CAS  Google Scholar 

  • Chiu TW, Young R, Chan LY, Burd A and Lo DY 2006 Plasma cell-free DNA as an indicator of severity of injury in burn patients. Clin. Chem. Lab. Med. 44 13–17

    PubMed  CAS  Google Scholar 

  • Choi JJ, Reich CF 3rd and Pisetsky DS 2005 The role of macrophages in the in vitro generation of extracellular DNA from apoptotic and necrotic cells. Immunology 115 55–62

    PubMed  CAS  Google Scholar 

  • Chorazy M, Bendich A, Borenfreund E, Ittensohp OL and Hutchison Dl 1963 Uptake of mammalian chromosomes by mammalian cells. J. Cell Biol. 19 71–77

    Google Scholar 

  • Coussens LM and Werb Z 2002 Inflammation and cancer. Nature 420 860–867

    PubMed  CAS  Google Scholar 

  • Dalpke A, Frank J, Peter M and Heeg K 2006 Activation of toll-like receptor 9 by DNA from different bacterial species. Infect Immun 74 940–946

    PubMed  CAS  Google Scholar 

  • Decker P 2006 Nucleosome autoantibodies. Clin. Chim. Acta 366 48–60

    PubMed  CAS  Google Scholar 

  • Decker P, Wolburg H and Rammensee HG 2003 Nucleosomes induce lymphocyte necrosis. Eur. J. Immunol. 33 1978–1987

    PubMed  Google Scholar 

  • Esposito D, Fassina G, Szabo P, De Angelis P, Rodgers L, Weksler M and Siniscalco M 1989 Chromosomes of older humans are more prone to aminopterin-induced breakage. Proc. Natl. Acad. Sci. USA 86 1302–1306

    PubMed  CAS  Google Scholar 

  • Fleischhacker M and Schmidt B 2007 Circulating nucleic acids (CNAs) and cancer--a survey. Biochim. Biophys. Acta 1775 181–232

    PubMed  CAS  Google Scholar 

  • Fleischhacker M, Schmidt B, Weickmann S, Fersching DM, Leszinski GS, Siegele B, Stötzer OJ, Nagel D, et al. 2011 Methods for isolation of cell-free plasma DNA strongly affect DNA yield. Clin. Chim. Acta 412 2085–2088

    PubMed  CAS  Google Scholar 

  • Fliedner TM, Graessle D, Paulsen C and Reimers K 2002 Structure and function of bone marrow hemopoiesis: mechanisms of response to ionizing radiation exposure. Cancer Biother. Radiopharm. 17 405–426

    PubMed  CAS  Google Scholar 

  • Franceschi C 2007 Inflammaging as a major characteristic of old people: can it be prevented or cured? Nutr. Rev. 65 S173-S176

    PubMed  Google Scholar 

  • Gahan PB, Anker P and Stroun M 2008 Metabolic DNA as the origin of spontaneously released DNA? Ann. NY Acad. Sci. 1137 7–17

    PubMed  CAS  Google Scholar 

  • Gahan PB and Stroun M 2010 The biology of circulating nucleic acids in plasma and serum (CNAPS); in Extracellular nucleic acids: Nucleic acids and molecular biology (eds) Y Kikuchi and E Rykova (Berlin Heidelberg: Springer-Verlag) 25 167–189

  • Gaipl US, Sheriff A, Franz S, Munoz LE, Voll RE, Kalden JR and Herrmann M 2006 Inefficient clearance of dying cells and autoreactivity. Curr. Topic Microbiol. Immunol. 305 161–176

    CAS  Google Scholar 

  • Gal S, Fidler C, Lo YM, Taylor M, Han C, Moore J, Harris AL and Wainscoat JS 2004 Quantitation of circulating DNA in the serum of breast cancer patients by real-time PCR. Br. J. Cancer 90 1211–1215

    PubMed  CAS  Google Scholar 

  • Galeazzi M, Morozzi G, Piccini M, Chen J, Bellisai F, Fineschi S and Marcolongo R 2003 Dosage and characterization of circulating DNA: present usage and possible applications in systemic autoimmune disorders. Autoimmun. Rev. 2 50–55

    PubMed  CAS  Google Scholar 

  • García-Olmo DC, Domínguez C, García-Arranz M, Anker P, Stroun M, García-Verdugo JM and García-Olmo D 2010 Cell-free nucleic acids circulating in the plasma of colorectal cancer patients induce the oncogenic transformation of susceptible cultured cells. Cancer Res. 70 560–567

    PubMed  Google Scholar 

  • Gartler SM 1959 Cellular uptake of deoxyribonucleic acid by human tissue culture cells. Nature 184 1505–1506

    PubMed  CAS  Google Scholar 

  • Gartler SM and Pavlovskis OR 1960 Demonstration of cellular uptake of polymerized DNA in mammalian cell cultures. Biochem. Biophys. Res. Commun. 3 127–131

    PubMed  CAS  Google Scholar 

  • Geiger S, Holdenrieder S, Stieber P, Hamann GF, Bruening R, Ma J, Nagel D and Seidel D 2006 Nucleosomes in serum of patients with early cerebral stroke. Cerebrovasc. Dis. 21 32–37

    PubMed  Google Scholar 

  • Hariton-Gazal E, Rosenbluh J, Graessmann A, Gilon C and Loyter A 2003 Direct translocation of histone molecules across cell membranes. J. Cell Sci. 116 4577–4586

    PubMed  CAS  Google Scholar 

  • Hefeneider SH, Cornell KA, Brown LE, Bakke AC, McCoy SL and Bennett RM 1992 Nucleosomes and DNA bind to specific cell-surface molecules on murine cells and induce cytokine production. Clin. Immunol. Immunopathol. 63 245–251

    PubMed  CAS  Google Scholar 

  • Holdenrieder S and Stieber P 2009 Clinical use of circulating nucleosomes. Crit. Rev. Clin. Lab. Sci. 46 1–24

    PubMed  CAS  Google Scholar 

  • Holdenrieder S, Eichhorn P, Beuers U, Samtleben W, Schoenermarck U, Zachoval R, Nagel D and Stieber P 2006 Nucleosomal DNA fragments in autoimmune diseases. Ann. NY Acad. Sci. 1075 318–327

    PubMed  CAS  Google Scholar 

  • Holdenrieder S, Nagel D, Schalhorn A, Heinemann V, Wilkowski R, von Pawel J, Raith H, Feldmann K, et al. 2008 Clinical relevance of circulating nucleosomes in cancer. Ann. NY Acad. Sci. 1137 180–189

    PubMed  CAS  Google Scholar 

  • Holdenrieder S, Stieber P, Bodenmüller H, Busch M, Fertig G, Fürst H, Schalhorn A, Schmeller N, et al. 2001a Nucleosomes in serum of patients with benign and malignant diseases. Int. J. Cancer 95 114–120

    PubMed  CAS  Google Scholar 

  • Holdenrieder S, Stieber P, Bodenmüller H, Busch M, Von Pawel J, Schalhorn A, Nagel D and Seidel D 2001b Circulating nucleosomes in serum. Ann. NY Acad. Sci. 945 93–102

    PubMed  CAS  Google Scholar 

  • Holdenrieder S, Stieber P, Bodenmüller H, Fertig G, Fürst H, Schmeller N, Untch M and Seidel D 2001c Nucleosomes in serum as a marker for cell death. Clin. Chem. Lab. Med. 39 596–605

    PubMed  CAS  Google Scholar 

  • Hsu FC, Kritchevsky SB, Liu Y, Kanaya A, Newman AB, Perry SE, Visser M, Pahor M, et al. 2009 Association between inflammatory components and physical function in the health, aging, and body composition study: a principal component analysis approach. J. Gerontol. A Biol. Sci. Med. Sci. 64 581–589

    PubMed  Google Scholar 

  • Huang ZH, Li LH and Hua D 2006 Quantitative analysis of plasma circulating DNA at diagnosis and during follow-up of breast cancer patients. Cancer Lett. 243 64–70

    PubMed  CAS  Google Scholar 

  • Iguchi H, Kosaka N and Ochiya T 2010 Secretory microRNAs as a versatile communication tool. Commun. Integr. Biol. 3 478–481

    PubMed  Google Scholar 

  • Ishii KJ, Suzuki K, Coban C, Takeshita F, Itoh Y, Matoba H, Kohn LD and Klinman DM 2001 Genomic DNA released by dying cells induces the maturation of APCs. J. Immunol. 167 2602–2607

    PubMed  CAS  Google Scholar 

  • Ittensohn OL and Hutchison DJ 1969 Cytologic manifestations of the phagocytosis of L1210 chromosomes by L1210 cells in culture. Exp. Cell Res. 55 149–154

    PubMed  CAS  Google Scholar 

  • Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, Hesch RD and Knippers R 2001 DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res. 61 1659–1665

    PubMed  CAS  Google Scholar 

  • Jung M, Klotzek S, Lewandowski M, Fleischhacker M and Jung K 2003 Changes in concentration of DNA in serum and plasma during storage of blood samples. Clin. Chem. 49 1028–1029

    PubMed  CAS  Google Scholar 

  • Jylhävä J, Kotipelto T, Raitala A, Jylhä M, Hervonen A and Hurme M 2011 Aging is associated with quantitative and qualitative changes in circulating cell-free DNA: the vitality 90+ study. Mech. Ageing Dev. 132 20–26

    PubMed  Google Scholar 

  • Karpfel Z, Šlotová J and Paleček E 1963 Chromosome aberrations produced by deoxyribonucleic acids in mice. Exp. Cell Res. 32 147–148

    PubMed  CAS  Google Scholar 

  • Kawane K, Fukuyama H, Kondoh G, Takeda J, Ohsawa Y, Uchiyama Y and Nagata S 2001 Requirement of DNase II for definitive erythropoiesis in the mouse fetal liver. Science 292 1546–1549

    PubMed  CAS  Google Scholar 

  • Kawane K, Ohtani M, Miwa K, Kizawa T, Kanbara Y, Yoshioka Y, Yoshikawa H and Nagata S 2006 Chronic polyarthritis caused by mammalian DNA that escapes from degradation in macrophages. Nature 443 998–1002

    PubMed  CAS  Google Scholar 

  • Kawasaki T, Kawai T and Akira S 2011 Recognition of nucleic acids by pattern-recognition receptors and its relevance in autoimmunity. Immunol. Rev. 243 61–73

    PubMed  CAS  Google Scholar 

  • Kawashima A, Tanigawa K, Akama T, Wu H, Sue M, Yoshihara A, Ishido Y, Kobiyama K, et al. 2011 Fragments of genomic DNA released by injured cells activate innate immunity and suppress endocrine function in the thyroid. Endocrinology 152 1702–1712

    PubMed  CAS  Google Scholar 

  • Koffler D, Agnello V, Winchester R and Kunkel HG 1973 The occurrence of single-stranded DNA in the serum of patients with systemic lupus erythematosus and other diseases. J. Clin. Invest. 52 198–204

    PubMed  CAS  Google Scholar 

  • Kok IP 1959 Dopov. Akad. Nauk. Ukr. RSR 12 1211

    Google Scholar 

  • Kopreski MS, Benko FA, Kwak LW and Gocke CD 1999 Detection of tumor messenger RNA in the serum of patients with malignant melanoma. Clin. Cancer Res. 5 1961–1965

    PubMed  CAS  Google Scholar 

  • Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y and Ochiya T 2010 Secretory mechanisms and intercellular transfer of microRNAs in living cells. J. Biol. Chem. 285 17442–17452

    PubMed  CAS  Google Scholar 

  • Kremer A, Wilkowski R, Holdenrieder S, Nagel D, Stieber P and Seidel D 2005 Nucleosomes in pancreatic cancer patients during radiochemotherapy. Tumour Biol. 26 44–49

    PubMed  CAS  Google Scholar 

  • Kuroi K, Tanaka C and Toi M 1999 Plasma nucleosome levels in node-negative breast cancer patients. Breast Cancer 6 361–364

    PubMed  Google Scholar 

  • Kuroi K, Tanaka C and Toi M 2001 Clinical significance of plasma nucleosome levels in cancer patients. Int. J. Oncol. 19 143–148

    PubMed  CAS  Google Scholar 

  • Kutzler MA and Weiner DB 2008 DNA vaccines: ready for prime time? Nat. Rev. Genet. 9 776–788

    PubMed  CAS  Google Scholar 

  • Lake JA, Jain R and Rivera MC 1999 Mix and match in the tree of life. Science 283 2027–2028

    PubMed  CAS  Google Scholar 

  • Lam NY, Rainer TH, Chan LY, Joynt GM and Lo YM 2003 Time course of early and late changes in plasma DNA in trauma patients. Clin. Chem. 49 1286–1291

    PubMed  CAS  Google Scholar 

  • Lam NY, Rainer TH, Chiu RW, Joynt GM and Lo YM 2004 Plasma mitochondrial DNA concentrations after trauma. Clin. Chem. 50 213–216

    PubMed  CAS  Google Scholar 

  • Lorenz C, Fotin-Mleczek M, Roth G, Becker C, Dam TC, Verdurmen WP, Brock R, Probst J and Schlake T 2011 Protein expression from exogenous mRNA: uptake by receptor-mediated endocytosis and trafficking via the lysosomal pathway. RNA Biol. 8 627–636

    PubMed  CAS  Google Scholar 

  • Lotze MT, Zeh HJ, Rubartelli A, Sparvero LJ, Amoscato AA, Washburn NR, Devera ME, Liang X, et al. 2007 The grateful dead: damage-associated molecular pattern molecules and reduction/oxidation regulate immunity. Immunol. Rev. 220 60–81

    PubMed  CAS  Google Scholar 

  • Lui YY, Woo KS, Wang AY, Yeung CK, Li PK, Chau E, Ruygrok P and Lo YM 2003 Origin of plasma cell-free DNA after solid organ transplantation. Clin. Chem. 49 495–496

    PubMed  CAS  Google Scholar 

  • Mahmoudi M, Mercer J and Bennett M 2006 DNA damage and repair in atherosclerosis. Cardiovasc Res. 71 259–268

    PubMed  CAS  Google Scholar 

  • Mancuso R, Hernis A, Cavarretta R, Caputo D, Calabrese E, Nemni R, Ferrante P, Delbue S, et al. 2010 Detection of viral DNA sequences in the cerebrospinal fluid of patients with multiple sclerosis. J. Med. Virol. 82 1051–1057

    PubMed  CAS  Google Scholar 

  • McBride OW and Peterson JL 1980 Chromosome-mediated gene transfer in mammalian cells. Annu. Rev. Genet. 14 321–345

    PubMed  CAS  Google Scholar 

  • Mehra N, Penning M, Maas J, van Daal N, Giles RH and Voest EE 2007 Circulating mitochondrial nucleic acids have prognostic value for survival in patients with advanced prostate cancer. Clin. Cancer Res. 13 421–426

    PubMed  CAS  Google Scholar 

  • Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, et al. 2008 Circulating microRNAs as stable blood-based markers for cancer detection. Proc. Natl. Acad. Sci. USA 105 10513–10518

    PubMed  CAS  Google Scholar 

  • Mueller S, Holdenrieder S, Stieber P, Haferlach T, Schalhorn A, Braess J, Nagel D and Seidel D 2006 Early prediction of therapy response in patients with acute myeloid leukemia by nucleosomal DNA fragments. BMC Cancer 6 143

    PubMed  Google Scholar 

  • Nagata S and Kawane K 2011 Autoinflammation by endogenous DNA. Adv. Immunol. 110 139–161

    PubMed  CAS  Google Scholar 

  • Nagata S, Hanayama R and Kawane K 2010 Autoimmunity and the clearance of dead cells. Cell 140 619–630

    PubMed  CAS  Google Scholar 

  • Nawroz H, Koch W, Anker P, Stroun M and Sidransky D 1996 Microsatellite alterations in serum DNA of head and neck cancer patients. Nat. Med. 2 1035–1037

    PubMed  CAS  Google Scholar 

  • Niu MC, Niu LC and Guha A 1968 The entrance of exogenous RNA into the mouse ascites cell. Proc. Soc. Exp. Biol. Med 128 550–555

    PubMed  CAS  Google Scholar 

  • Nusbaum NJ 1998 The aging/cancer connection. Am J. Med. Sci. 315 40–49

    CAS  Google Scholar 

  • O'Brien BA, Geng X, Orteu CH, Huang Y, Ghoreishi M, Zhang Y, Bush JA, Li G, et al. 2006 A deficiency in the in vivo clearance of apoptotic cells is a feature of the NOD mouse. J. Autoimmun. 26 104–115

    PubMed  Google Scholar 

  • Ochman H, Lawrence JG and Groisman EA 2000 Lateral gene transfer and the nature of bacterial innovation. Nature 405 299–304

    PubMed  CAS  Google Scholar 

  • Peters DL and Pretorius PJ 2011 Origin, translocation and destination of extracellular occurring DNA--a new paradigm in genetic behaviour. Clin. Chim. Acta 412 806–811

    PubMed  CAS  Google Scholar 

  • Pisetsky DS 2007 The role of nuclear macromolecules in innate immunity. Proc Am. Thorac. Soc. 4 258–262

    PubMed  CAS  Google Scholar 

  • Pisetsky DS and Ullal AJ 2010 The blood nucleome in the pathogenesis of SLE. Autoimmun. Rev. 10 35–37

    PubMed  CAS  Google Scholar 

  • Pritchard CC, Kroh E, Wood B, Arroyo JD, Dougherty KJ, Miyaji MM, Tait JF and Tewari M 2011 Blood cell origin of circulating microRNAs: a cautionary note for cancer biomarker studies. Cancer Prev. Res. (Phila) doi:10.1158/1940–6207.CAPR-11–0370

  • Rhodes A, Wort SJ, Thomas H, Collinson P and Bennett ED 2006 Plasma DNA concentration as a predictor of mortality and sepsis in critically ill patients. Crit. Care 10 R60

    PubMed  Google Scholar 

  • Rock KL, Lai JJ and Kono H 2011 Innate and adaptive immune responses to cell death. Immunol. Rev. 243 191–205

    PubMed  CAS  Google Scholar 

  • Rykova EY, Laktionov PP and Vlassov VV 2010 Circulating nucleic acids in health and disease; in Extracellular nucleic acids: Nucleic acids and molecular biology (eds) Y Kikuchi and E Rykova (Berlin Heidelberg: Springer-Verlag) 25 93–128

  • Salgame P, Varadhachary AS, Primiano LL, Fincke JE, Muller S and Monestier M 1997 An ELISA for detection of apoptosis. Nucleic Acids Res. 25 680–681

    PubMed  CAS  Google Scholar 

  • Saukkonen K, Lakkisto P, Pettilä V, Varpula M, Karlsson S, Ruokonen E, Pulkki K and Finnsepsis Study Group 2008 Cell-free plasma DNA as a predictor of outcome in severe sepsis and septic shock. Clin. Chem. 54 1000–1007

    PubMed  CAS  Google Scholar 

  • Schöler N, Langer C and Kuchenbauer F 2011 Circulating microRNAs as biomarkers - True Blood? Genome Med. 3 72

    PubMed  Google Scholar 

  • Schwarzenbach H, Hoon DS and Pantel K 2011 Cell-free nucleic acids as biomarkers in cancer patients. Nat. Rev. Cancer 11 426–437

    PubMed  CAS  Google Scholar 

  • Shackelford DA 2006 DNA end joining activity is reduced in Alzheimer's disease. Neurobiol. Aging 27 596–605

    PubMed  CAS  Google Scholar 

  • Shacter E and Weitzman SA 2002 Chronic inflammation and cancer. Oncology (Williston Park) 16 217–226, 229; discussion 230–2

    Google Scholar 

  • Shanmugam G and Bhargava PM 1966 The uptake of homologous ribonucleic acid by rat-liver parenchymal cells in suspension. Biochem. J. 99 297–307

    PubMed  CAS  Google Scholar 

  • Shanmugam G and Bhargava PM 1969 Uptake of Escherichia coli RNA by rat liver cells in suspension. Indian J. Biochem. 6 64–70

    PubMed  CAS  Google Scholar 

  • Shapiro B, Chakrabarty M, Cohn EM and Leon SA 1983 Determination of circulating DNA levels in patients with benign or malignant gastrointestinal disease. Cancer 51 2116–2120

    PubMed  CAS  Google Scholar 

  • Shaw JA, Page K, Blighe K, Hava N, Guttery D, Ward B, Brown J, Ruangpratheep C, et al. 2012 Genomic analysis of circulating cell-free DNA infers breast cancer dormancy. Genome Res. 22 220–231

    PubMed  CAS  Google Scholar 

  • Sozzi G, Conte D, Mariani L, Lo Vullo S, Roz L, Lombardo C, Pierotti MA and Tavecchio L 2001 Analysis of circulating tumor DNA in plasma at diagnosis and during follow-up of lung cancer patients. Cancer Res. 61 4675–4678

    PubMed  CAS  Google Scholar 

  • Stegemann S and Bock R 2009 Exchange of genetic material between cells in plant tissue grafts. Science 324 649–651

    PubMed  CAS  Google Scholar 

  • Stephens PJ, McBride DJ, Lin ML, Varela I, Pleasance ED, Simpson JT, Stebbings LA, Leroy C, et al. 2009 Complex landscapes of somatic rearrangement in human breast cancer genomes. Nature 462 1005–1010

    PubMed  CAS  Google Scholar 

  • Suzuki K, Mori A, Ishii KJ, Saito J, Singer DS, Klinman DM, Krause PR and Kohn LD 1999 Activation of target-tissue immune-recognition molecules by double-stranded polynucleotides. Proc. Natl. Acad. Sci. USA 96 2285–2290

    PubMed  CAS  Google Scholar 

  • Swarup V and Rajeswari MR 2007 Circulating (cell-free) nucleic acids--a promising, non-invasive tool for early detection of several human diseases. FEBS Lett. 581 795–799

    PubMed  CAS  Google Scholar 

  • Szybalska EH and Szybalski W 1962 Genetics of human cell lines. IV. DNA-mediated heritable transformation of a biochemical trait. Proc. Natl. Acad. Sci. USA 48 2026–2034

    PubMed  CAS  Google Scholar 

  • Szybalski W, Szybalska EH and Ragni G 1962 Genetic studies with human cell lines. Natl. Cancer Inst. Monogr. 7 75–89

    Google Scholar 

  • Tan EM 1989 Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv. Immunol. 44 93–151

    PubMed  CAS  Google Scholar 

  • Tan EM, Schur PH, Carr RI and Kunkel HG 1966 Deoxyribonucleic acid [DNA] and antibodies to DNA in the serum of patients with systemic lupus erythematosus. J. Clin. Invest. 45 1732 –1740

    PubMed  CAS  Google Scholar 

  • Tanner JE 2004 Nucleosomes activate NF-kappaB in endothelial cells for induction of the proangiogenic cytokine IL-8. Int. J. Cancer 112 155–160

    PubMed  CAS  Google Scholar 

  • Trejo-Becerril C, Pérez-Cárdenas E, Treviño-Cuevas H, Taja-Chayeb L, García-López P, Segura-Pacheco B, Chávez-Blanco A, Lizano-Soberon M, et al. 2003 Circulating nucleosomes and response to chemotherapy: an in vitro, in vivo and clinical study on cervical cancer patients. Int. J. Cancer 104 663–668

    PubMed  CAS  Google Scholar 

  • Tsai NW, Lin TK, Chen SD, Chang WN, Wang HC, Yang TM, Lin YJ, Jan CR, et al. 2011 The value of serial plasma nuclear and mitochondrial DNA levels in patients with acute ischemic stroke. Clin. Chim. Acta 412 476–479

    PubMed  CAS  Google Scholar 

  • Umetani N, Giuliano AE, Hiramatsu SH, Amersi F, Nakagawa T, Martino S and Hoon DS 2006 Prediction of breast tumor progression by integrity of free circulating DNA in serum. J. Clin Oncol. 24 4270–4276

    PubMed  CAS  Google Scholar 

  • van der Vaart M and Pretorius PJ 2007 The origin of circulating free DNA. Clin. Chem. 53 2215

    PubMed  Google Scholar 

  • van der Vaart M and Pretorius PJ 2008 Circulating DNA. Its origin and fluctuation. Ann. NY Acad. Sci. 1137 18–26

    PubMed  Google Scholar 

  • van der Vaart M and Pretorius PJ 2010 Is the role of circulating DNA as a biomarker of cancer being prematurely overrated? Clin. Biochem. 43 26–36

    PubMed  Google Scholar 

  • Vlassov VV, Laktionov PP and Rykova EY 2010 Circulating nucleic acids as a potential source for cancer biomarkers. Curr. Mol. Med. 10 142–165

    PubMed  CAS  Google Scholar 

  • Wagstaff KM, Fan JY, De Jesus MA, Tremethick DJ and Jans DA 2008 Efficient gene delivery using reconstituted chromatin enhanced for nuclear targeting. FASEB J. 22 2232–2242

    PubMed  CAS  Google Scholar 

  • Watson K, Gooderham NJ, Davies DS and Edwards RJ 1999 Nucleosomes bind to cell surface proteoglycans. J. Biol. Chem. 274 21707–21713

    PubMed  CAS  Google Scholar 

  • Wentz-Hunter KK and Potashkin JA 2011 The role of miRNAs as key regulators in the neoplastic microenvironment. Mol. Biol. Int. 2011 839872

    PubMed  CAS  Google Scholar 

  • Wieczorek AJ, Sitaramam V, Machleidt W, Rhyner K, Perruchoud AP and Block LH 1987 Diagnostic and prognostic value of RNA-proteolipid in sera of patients with malignant disorders following therapy: first clinical evaluation of a novel tumor marker. Cancer Res. 47 6407–6412

    PubMed  CAS  Google Scholar 

  • Williams RC Jr, Malone CC, Meyers C, Decker P and Muller S 2001 Detection of nucleosome particles in serum and plasma from patients with systemic lupus erythematosus using monoclonal antibody 4H7. J. Rheumatol. 28 81–94

    PubMed  CAS  Google Scholar 

  • Woll E 1953 Einwirkung von nucleinsäuren und ihren baustoffen auf die wurzelspitzenmitose. Chromosoma 5 391–427

    PubMed  CAS  Google Scholar 

  • Xu J, Zhang X, Pelayo R, Monestier M, Ammollo CT, Semeraro F, Taylor FB, Esmon NL, et al. 2009 Extracellular histones are major mediators of death in sepsis. Nat. Med. 15 1318–1321

    PubMed  CAS  Google Scholar 

  • Yoon CH 1964 Bases for failure to induce transformation in vivo with exogenous, homologous DNA: I. Incorporation in mice of P32 and C14 labels of donor DNA into recipient gonad DNA. J. Hered. 55 163–167

    PubMed  CAS  Google Scholar 

  • Yoon CH and Sabo J 1964 Bases for failure to induce transformation in vivo with exogenous, homologous DNA in mice: Autoradiographic investigation of incorporation of exogenous DNA labeled with 3H-thymidine into germ cells. Exp. Cell Res. 34 599–602

    PubMed  CAS  Google Scholar 

  • Yosida TH and Sekiguchi T 1968 Metaphase figures of rat chromosomes incorporated into mouse cells. Mol Gen Genet. 103 253–257

    PubMed  CAS  Google Scholar 

  • Zachariah RR, Schmid S, Buerki N, Radpour R, Holzgreve W and Zhong X 2008 Levels of circulating cell-free nuclear and mitochondrial DNA in benign and malignant ovarian tumors. Obstet. Gynecol. 112 843–850

    PubMed  CAS  Google Scholar 

  • Zeerleder S, Zwart B, Wuillemin WA, Aarden LA, Groeneveld ABJ, Caliezi C, van Nieuwenhuijze AEM, van Mierlo GJ, et al. 2003 Elevated nucleosome levels in systemic inflammation and sepsis. Crit. Care Med. 31 1947–1951

    PubMed  CAS  Google Scholar 

  • Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, Brohi K, Itagaki K, et al. 2010 Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464 104–107

    PubMed  CAS  Google Scholar 

  • Zhong S, Ng MC, Lo YM, Chan JC and Johnson PJ 2000 Presence of mitochondrial tRNA(Leu(UUR)) A to G 3243 mutation in DNA extracted from serum and plasma of patients with type 2 diabetes mellitus. J. Clin. Pathol. 53 466–469

    PubMed  CAS  Google Scholar 

  • Zhong XY, Gebhardt S, Hillermann R, Tofa KC, Holzgreve W and Hahn S 2005 Circulatory nucleosome levels are significantly increased in early and late-onset preeclampsia. Prenat. Diagn. 25 700–703

    PubMed  Google Scholar 

  • Zimmermann BG, ParK NJ and Wong DT 2007 Genomic targets in saliva. Ann. NY Acad. Sci. 1098 184–191

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Translational Research, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, 410 210, India

    Indraneel Mittra, Naveen Kumar Nair & Pradyumna Kumar Mishra

Authors
  1. Indraneel Mittra
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Naveen Kumar Nair
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pradyumna Kumar Mishra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Indraneel Mittra.

Additional information

Corresponding editor: Durgadas P Kasbekar

MS received 27 February 2012; accepted 06 March 2012

Corresponding editor: durgadas p kasbekar

[Mittra I, Nair NK and Mishra PK 2012 Nucleic acids in circulation: Are they harmful to the host? J. Biosci. 37 1–12] DOI 10.1007/s12038-012-9192-8

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mittra, I., Nair, N.K. & Mishra, P.K. Nucleic acids in circulation: Are they harmful to the host?. J Biosci 37, 301–312 (2012). https://doi.org/10.1007/s12038-012-9192-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12038-012-9192-8

Keywords

Search

Navigation