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Anti-HMdU Autoantibodies in Human Sera as a Biomarker of Cancer Risk

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Tumor Marker Protocols

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 14))

Abstract

Our laboratory has discovered that blood sera of healthy men and women contain low levels of anti-HMdU (Shydroxymethyl-2′-deoxyuridine, an oxidized thymidine) autoantibodies (aAbs) (1,2) However, patients with chronic inflammatory diseases exhibit elevated anti-HMdU aAb titers. Interestingly, people at high risk for cancer, those with cancer and, most importantly, those who were diagnosed with breast, colon, and rectal cancer 0.5–6 yr after donation of the blood samples we analyzed (but not those diagnosed with nonmelanoma skin cancer) had significantly elevated anti-HMdU aAb titers (4). The high aAbs in apparently healthy women at the time of blood donation persisted for several years before diagnosis (3). We recently also showed that these anti-HMdU aAb titers depend on subject’s age and menopausal status (5) Our findings pomt to anti-HMdU aAb titers as being a biomarker of a potential to develop cancer even in the absence of family risk factors, which constitute the majority of cases

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References

  1. Frenkel K., Karkoszka J., Kim E, and Taioli E. (1993) Recognition of oxidized DNA bases by sera of patients with inflammatory disease. Free Rad. Biol Med 14, 483–494

    Article  PubMed  CAS  Google Scholar 

  2. Frenkel K., Karkoszka J, Glassman T, Dubin N, Toniolo P, Taioli E, Mooney L, and Kato I (1997) Serum autoantibodies recognizing 5-hydroxy-methyl-2′-deoxyuridine, an oxidized DNA base, as biomarkers of cancer risk in women Cancer Epidemiology Blomarkers and Prevention, in press.

    Google Scholar 

  3. Frenkel K, Glassman T, Karkoszka J, and Taroh E (1994) Anti-oxidized DNA base autoantibodies as a potential biomarker of high risk for the development of human breast cancer Proc. Am Assoc. Cancer Res 35, 97

    Google Scholar 

  4. Frenkel K., Karkoszka J., Glassman T, Powell J, Pero R, Tomolo P, and Tatoli E (1995) Autoantibodies that recognize oxidized DNA bases as biomarkers of cancer risk Proc Am Assoc. Cancer Res 36, 284

    Google Scholar 

  5. Djuric Z, Heilbrun L K, Simon M. S, Luongo D A, LoRusso P M, and Martino S (1996) Levels of.5-hydroxymethyl-2′-deoxyuridine in blood DNA as a marker of breast cancer risk Cancer 77, 69l–696

    Article  Google Scholar 

  6. Djuric Z., Heilbrun L K, Reading B. A, Boomer A, Valeriote F. A, and Martino S. (1991) Effects of a low fat diet on levels of oxidative damage to DNA in human peripheral nucleated blood cells J Natl Cancer Inst 83, 766–769

    Article  PubMed  CAS  Google Scholar 

  7. Malins D C and Haimanot R (1991) Major alterations in the nucleotide structure IN DNA in cancer of the female breast Cancer Res 51, 5430–5432.

    PubMed  CAS  Google Scholar 

  8. Dunham L. J (1972) Cancer in man at a site of prior benign lesion of skin or mucous membrane: a review. Cancer Res 32, 1359–1374

    PubMed  CAS  Google Scholar 

  9. Weitzman S. A. and Gordon L. I. (1990) Inflammation and cancer: role of phagocyte-generated oxidants In carcinogenesis. Blood 76, 655–663

    PubMed  CAS  Google Scholar 

  10. Frenkel K (1992) Carcinogen-mediated oxidant formation and oxidative DNA damage. Pharmac Ther 53, 127–166.

    Article  CAS  Google Scholar 

  11. Breimer L H (1990) Molecular mechanisms of oxygen radical carcinogenesis and mutagenesis: the role of DNA base damage. Mol Carcinogenesis 3, 188–197.

    Article  CAS  Google Scholar 

  12. Teebor G W, Boorstein R J, and Cadet J. (1988) The repairability of oxidative free radical mediated damage to DNA: a review. Int J Radiat. Biol 54, 13l–150

    Article  Google Scholar 

  13. Trush M. A. and Kensler T W. (1991) An overview of the relationship between oxidative stress and chemical carcinogenesis. Free Rad Biol Med 10, 201–209

    Article  PubMed  CAS  Google Scholar 

  14. Frenkel K., Wei L., and Wei H. (1995) 7,12-Dimethylbenz[a]anthracene Induces oxidative DNA modification In vivo. Free Rad. Biol Med 19, 373–380.

    Article  CAS  Google Scholar 

  15. Liehr J. G and Roy D. (1990) Free radical generation by redox cycling of estrogens Free Rad Biol Med 8, 415–423.

    Article  PubMed  CAS  Google Scholar 

  16. Dipple A, Pigott M. A, Bigger A. H., and Blake D M. (1984) 7,12-Dimethyl-benz[a]anthracene-DNA binding in mouse skin: response of different mouse strains and effects of vartous modifiers of carcinogenesis. Carcinogenesis 5, 1087–1090.

    Article  PubMed  CAS  Google Scholar 

  17. McCormick D L, Major N, and Moon R C (1984) Inhibition of 7,12-dim-ethyl-benz[a]anthracene-induced rat mammary carcinogenesis by concomitant or postcarcinogen antioxidant exposure Cancer Res 44, 2858–2863

    PubMed  CAS  Google Scholar 

  18. Wattenberg L W (1980) Inhibition of chemical carcinogenesis by antioxidants, in tiCarcinogenesis, Vol 5, Modifiers of Chemical Carcinogenesis (Slaga T J, ed), Raven Press, New York, pp 85–98

    Google Scholar 

  19. Perchellet J.-P and Perchellet E M (1989) Antioxidants and multistage carcinogenesis in mouse skin. Free Rad Biol Med 7, 377–408

    Article  PubMed  CAS  Google Scholar 

  20. Wet H. and Frenkel K. (1993) Relationship of oxidative events and DNA oxidation in SENCAR mice to in vivo promoting activity of phorbol ester-type tumor promoters. Carcinogenesis 14, 1195–1201.

    Article  Google Scholar 

  21. Bhimani R. S, Troll W, Grunberger D, and Frenkel K (1993) Inhibition of oxidative stress in HeLa cells by chemopreventive agents Cancer Res 53, 4528–4533

    PubMed  CAS  Google Scholar 

  22. Frenkel K, Wet H, Bhimani R, Ye J., Zadunaisky J A, Huang M-T, Ferraro T., Conney A. H, and Grunberger D. (1993) Inhibition of tumor promoter-mediated processes in mouse skin and bovine lens by caffeic acid phenethyl ester Cancer Res 53, 1255–1261.

    PubMed  CAS  Google Scholar 

  23. Huang M-T, Ma W, Yen P, Xie J-Q., Han J, Frenkel K, Grunberger D, and Conney A H (1996) Inhibitory effects of caffeic acid phenethyl ester (CAPE) on 12-O-tetradecanoyl-phorbol-13-acetate-induced tumor promotion in mouse skin and the synthesis of DNA, RNA and protein in HeLa cells Carcinogenesis 17, 761–765

    Article  PubMed  CAS  Google Scholar 

  24. Wet H and Frenkel K (1992) Suppression of tumor promoter-induced oxidative events and DNA damage in vivo by sarcophytol A a possible mechanism of anti-promotion. Cancer Res 52, 2298–2303

    Google Scholar 

  25. Bhimani R. S, Zhong Z., Schleifer E, Troll W, and Frenkel K (1995) Human promyelocytic leukemia cells (HL-60), a new model to study the effects of chemopreventive agents on H2O2 production Cancer Detect Prev 9, 292–298

    Google Scholar 

  26. Lim J. S, Frenkel K, and Troll W (1992) Tamoxifen suppresses tumor promoter-induced hydrogen peroxide formation by human neutrophils Cancer Res 52, 4969–4972

    PubMed  CAS  Google Scholar 

  27. Frenkel K, Chrzan K, Ryan C A, Wiesner R, and Troll W (1987) Chymot-rypsin-specific protease inhibitors decrease H2O2 formation by activated human polymorphonuclear leucocytes. Carcinogenesis 8, 1207–1212

    Article  PubMed  CAS  Google Scholar 

  28. Frenkel K., Karkoszka J, Cohen B, Baranski B., Jakubowski M., Cosma G, Taioli E., and Toniolo P. (1994) Occupational exposures to Cd, N1 and Cr modulate titers of anti-oxidized DNA base autoantibodies. Environ Health Perspect 102(Suppl. 3), 221–225

    PubMed  CAS  Google Scholar 

  29. Frenkel K. (1996) U S. Patent No 5,552,285 Immunoassays methods, compositions and kits for antibodies to oxidized DNA bases

    Google Scholar 

  30. Tatoli E, Kinney P, Zhitkovich A., Fulton H, Voitkun V, Cosma G, Frenkel K, Tomolo P, Garte S, and Costa M. (1994) Application of rehabtlity models to studies of biomarker validation Environ Health Perspect 102, 306–309

    Article  Google Scholar 

  31. Erlanger B F. and Beiser S M. (1964) Antibodies specific for ribonucleosides and ribonucleotides and their reaction with DNA Proc Natl Acad Sci USA 52, 68–74

    Article  PubMed  CAS  Google Scholar 

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© 1998 Humana Press Inc, Totowa, NJ

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Frenkel, K., Karkoszka, J. (1998). Anti-HMdU Autoantibodies in Human Sera as a Biomarker of Cancer Risk. In: Hanausek, M., Walaszek, Z. (eds) Tumor Marker Protocols. Methods in Molecular Medicine™, vol 14. Springer, Totowa, NJ. https://doi.org/10.1385/0-89603-380-5:431

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  • DOI: https://doi.org/10.1385/0-89603-380-5:431

  • Publisher Name: Springer, Totowa, NJ

  • Print ISBN: 978-0-89603-380-1

  • Online ISBN: 978-1-59259-598-3

  • eBook Packages: Springer Protocols

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