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Oxidatively Damaged DNA: A Possible Antigenic Stimulus for Cancer Autoantibodies

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Abstract

Reactive oxygen species (ROS) are cytotoxic at higher concentration resulting in cell death, mutations, chromosomal aberrations or carcinogenesis. In this study DNA was modified by singlet oxygen and superoxide anion radicals generated by illumination of riboflavin under 365 nm UV-light. The modified DNA induced high titre antibodies in experimental animals. In enzyme immunoassay, serum antibodies from cancer patients (n = 34) showed a higher recognition of the modified DNA, as compared to the native form. This was further confirmed by the gel-shift assay. Immune IgG were used as a probe to detect oxidative lesions in the DNA of cancer patients. DNA isolated from lymphocytes of cancer patients proved to be an appreciable inhibitor of the experimentally induced antibodies against the ROS-DNA. This indicates the presence of oxidative lesions in the DNA obtained from cancer patients. The results show that ROS induced oxidative damage to DNA in cancer patients generate neo-epitopes that are alien for the immune system, resulting in autoantibody formation.

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References

  1. Valko M, Izakovic M, Mazur M, Rhodes CJ, Telser J. Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem. 2004;66:37–56.

    Article  Google Scholar 

  2. Lau AT, Wang Y, Chiu JF. Reactive oxygen species: current knowledge and applications in cancer research and therapeutic. J Cell Biochem. 2008;15:657–67.

    Article  Google Scholar 

  3. Ha HC, Sirisoma NS, Kuppusamy P, Zweier JL, Woster PM, Casero RA. The natural polyamine spermine functions directly as a free radical scavenger. Proc Natl Acad Sci USA. 1998;95:11140–5.

    Article  CAS  PubMed  Google Scholar 

  4. Halliwell B, Vitamin C. Poison, prophylactic or panacea? Trends Biochem Sci. 1999;24:255259.

    Article  Google Scholar 

  5. Oyagbemi AA, Azeez OL, Saba AB. Interaction between reactive oxygen species and cancer: the roles of natural dietary antioxidants and their molecular mechanisms of action. Asian Pac J Cancer Prev. 2009;10:535–44.

    PubMed  Google Scholar 

  6. Ahsan H, Ali A, Ali R. Oxygen free radicals and systemic autoimmunity. Clin Exp Immunol. 2003;131:398–404.

    Article  CAS  PubMed  Google Scholar 

  7. Dreher D, Junod AF. Role of oxygen free radicals in cancer development. Eur J Cancer. 1996;32:30–8.

    Article  Google Scholar 

  8. Athar M. Oxidative stress and experimental carcinogenesis. Indian J Exp Biol. 2002;40:656–67.

    CAS  PubMed  Google Scholar 

  9. Pagoria D, Lee A, Geurtsen W. The effect of camphorquinone (CQ) and CQ-related photosensitizers on the generation of reactive oxygen species and the production of oxidative DNA damage. Biomaterials. 2005;26:4091–9.

    Article  CAS  PubMed  Google Scholar 

  10. Box HC, Freund HG, Budzinski E, Waliace JC, Maccabin AE. Free radical induced base lesions. Radiat Res. 1995;141:91–4.

    Article  CAS  PubMed  Google Scholar 

  11. Epe In B, Halliwell B, Arouma OI, editors. DNA and free radicals. Chichester, UK: Ellis Horwood; 1993. p. 41–65.

    Google Scholar 

  12. Halliwell B, Arouma OP. DNA damage by oxygen derived species: its mechanism and measurement in mammalian systems. FEBS Lett. 1991;281:9–19.

    Article  CAS  PubMed  Google Scholar 

  13. Cadet J, Decarroz C, Wang SY, Midden WR. Mechanisms and products of photosensitizer degradation of nucleic acids and related model compounds. Israel J Chem. 1983;23:420–9.

    CAS  Google Scholar 

  14. Piette J, Calberg-Bacq CM, Lopez M, Van de Vorst A. Termination of DNA synthesis on proflavine and light treated OX174 single-stranded DNA. Biochim Biophys Acta. 1984;781:257–64.

    CAS  PubMed  Google Scholar 

  15. Kuchino Y, Mori F, Kasai H, Ohtsuka E, Nishimura S. Misreading of DNA templates containing 8-hydroxydeoxy guanosine at the modified base and at adjacent residues. Nature. 1987;327:77–9.

    Article  CAS  PubMed  Google Scholar 

  16. Wood ML, Dizdaroglu M, Gajewski A, Essingmann JM. Mechanistic studies of ionizing radiation and oxidative mutagenesis: genetic effects of a single 8-hydroxyguanine (7-hydro-8-oxoguanine) residue inserted at a unique site in a viral genome. Biochemistry. 1990;29:7024–32.

    Article  CAS  PubMed  Google Scholar 

  17. Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact. 2006;160:1–4.

    Article  CAS  PubMed  Google Scholar 

  18. Waris G, Ahsan H, Alam K. Evidence for the possible involvement of O ·−2 modified DNA in the etiopathogenesis of systemic lupus erythematosus. J Biochem Mol Biol Biophys. 1999;4:9–16.

    Google Scholar 

  19. Ali R, Alam K. Evaluation of antibodies against free radical modified DNA by ELISA. In: Armstrong D, editor. Oxidative stress biomarkers and antioxidants protocols. Totowa, NJ: Humana Press; 2002. p. 171–81.

    Chapter  Google Scholar 

  20. Dixit K, Ali R. Antigen binding characteristics of antibodies induced against nitric oxide modified plasmid DNA. Biochimica Biophysica Acta. 2001;1528:1–8.

    CAS  Google Scholar 

  21. Tasneem S, Ali R. Binding of SLE autoantibodies to native poly (I), ROS-poly (I) and native DNA: a comparative study. J Autoimmun. 2001;17:199–205.

    Article  CAS  PubMed  Google Scholar 

  22. Seifried HE, McDonald SS, Anderson DE, Greenwald P, Milner JA. The antioxidant conundrum in cancer. Cancer Res. 2003;63:4295–8.

    CAS  PubMed  Google Scholar 

  23. Ames BN. Endogenous oxidative DNA damage, aging and cancer. Free Radic Res Commun. 1989;7:121–8.

    Article  CAS  PubMed  Google Scholar 

  24. Jansson G. Formation of antibodies to native DNA in rats after administration of native DNA treated with xanthine-xanthine oxidase system. Free Radic Res Commun. 1985;1:119–22.

    Article  CAS  PubMed  Google Scholar 

  25. Ames BN, Shigenaga MK, Gold LS. DNA lesions, inducible DNA repair, and cell division: three key factors in mutagenesis and carcinogenesis. Environ Health Perspect. 1993;101:35–44.

    Article  CAS  PubMed  Google Scholar 

  26. Ames BN, Gold LS, Willett WC. The causes and prevention of cancer. Proc Natl Acad Sci USA. 1995;92:5258–65.

    Article  CAS  PubMed  Google Scholar 

  27. Leanderson P, Agesson CT. Cigarette smoke-induced DNA-damage: role of hydroquinone and catechol in the formation of the oxidative DNA adduct 8-hydroxydeoxyguanosine. Chem Biol Interact. 1990;75:71–81.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Financial assistance in the form of research grant (61/2/99-BMS-II) to Dr. Moinuddin from the Indian Council of Medical Research, New Delhi is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Medicine, J.N. Medical College, Aligarh Muslim University, Aligarh, 202002, Uttar Pradesh, India

    Saba Khan,  Moinuddin, Roshan Alam & Asif Ali

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  1. Saba Khan
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  2. Moinuddin
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  3. Roshan Alam
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  4. Asif Ali
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Correspondence to Asif Ali.

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Khan, S., Moinuddin, Alam, R. et al. Oxidatively Damaged DNA: A Possible Antigenic Stimulus for Cancer Autoantibodies. Indian J Clin Biochem 25, 244–249 (2010). https://doi.org/10.1007/s12291-010-0061-7

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  • DOI: https://doi.org/10.1007/s12291-010-0061-7

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