Skip to main content
Log in

Increased Hepatic Oxidative DNA Damage in Patients with Hepatocellular Carcinoma

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Since oxidative DNA damage plays a role in experimental carcinogen-induced cancers, the purpose of the present study was to determine if hepatic oxidative DNA damage was increased in patients with HCC compared to patients with benign hepatic tumors or hepatic metastases (non-HCC) or to patients with end-stage alcoholic liver disease undergoing liver transplantation. Oxidative DNA damage was assessed by 8-hydroxy-2`-deoxyguanosine (8-OH-dG). Results showed that peritumoral 8-OH-dG was markedly increased in HCC (N= 51) (180 ± 74 vs 32 ± 58-OH-dG/106dG for tumor, P < 0.005) in contrast to patients with non-HCC (N = 17), in whom the peritumoral 8-OH-dG did not differ from that in tumor (39 ± 7 vs. 31 ± 108-OH-dG/106dG). Oxidative DNA damage can be both mutagenic and carcinogenic; our data suggested it will be important in future studies to determine the chronology of this type of liver injury relative to hepatocarcinogenesis.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Parkin DM, Whelan SL, Ferlay J, Raymond I, Young J (eds): Cancer Incidence in Five Continents, Vol. VII. IARC Scientific Publication No. 143, Lyon, IARC, 1997

    Google Scholar 

  2. El-Serag HB, Mason AC: Rising incidence of heptocellular carcinoma in the United States. N Engl J Med 340(10):745–749, 1999

    Google Scholar 

  3. Ishak KG: Hepatocellular carcinoma associated with the inherited metabolic diseases. Etiology, Pathology, and Treatment of Hepatocellular Carcinoma in North America. In E Tabor, AM Di Bisceglie, RH Purcell (eds). Advances in Applied Biotechnology Series 13. Portfolio Publishing, Co. 1990, PP 91–103

  4. Ross RK, Yuan JM, Yu MC, Wogan GN, Qian GS, Tu JT, Groopman JD, Gao YT, Henderson BE: Urinary aflatoxin biomarkers and risk of hepato-cellular carcinoma. Lancet 339:943, 1992

    Google Scholar 

  5. Shimoda R, Nagashima M, Sakamoto M, Yamaguchi N, Hirohashi S, Yokot I, Kasai H: Increased formation of oxidative DNA damage, 8-hydroxydeoxyguanosine, in human livers with chronic hepatitis. Cancer Res 54:3171–3172, 1994

    Google Scholar 

  6. Britton RS: Hepatic injury in chronic iron overload. Role of lipid peroxidation. Chem Biol Interact 70(3- 4):183–226, 1989

    Google Scholar 

  7. Albano E, Poli G, Tomasi A, Dianzini MV: Free radical mechanisms in alcohol-mediated liver injury, Chronic Liver Damage. In MV Dianzini, B Gentilini (eds). New York, Excerpta Medica 1990, PP 27–38

    Google Scholar 

  8. Shen HM, Shi CY, Shen Y, Ong CN: Detection of elevated reactive oxygen species level in cultured rat hepatocytes treated with aflatoxin B1. Free Radic Biol Med 21(2):139–146, 1996

    Google Scholar 

  9. Trush MA, Kensler TW: An overview of the relationship between oxidative stress and chemical carcinogenesis. Free Radic Biol Med 10:201–209, 1991

    Google Scholar 

  10. Shigenaga MK, Ames BN: Assays for 8-hydroxy-2-deoxyguanosine: A biomarker of in vivo oxidative DNA damage. Free Radic Biol Med 10:211–216, 1991

    Google Scholar 

  11. Marmur J: A procedure for the isolation of deoxyribonucleic acid from microorganisms. J Mol Biol 3:208–218, 1961

    Google Scholar 

  12. Conway CC, Guonie G, Hussain NS, Fiala ES: Comparison of oxidative damage to rat liver DNA and RNA by primary nitroalkanes, secondary nitroalkanes, cyclopentanone oxime, and related compounds. Cancer Res 51:3143–3152, 1991

    Google Scholar 

  13. Torrance JD, Bothwell TH: Tissue iron stores. Methods in Hematol 1:90–115, 1980

    Google Scholar 

  14. Baker BL, Di Bisceglie AM, Kaneko S, Miller R, Feinstone SM, Waggoner JG, Hoofnagle JH: Determination of hepatitis B virus DNA in serum using the polymerase chain reaction: Clinical significance and correlation with serological and biochemical markers. Hepatology 13:632–636, 1991

    Google Scholar 

  15. Abdel-Hamid H, Edelman DC, Highsmith WE, Constantine NT: Optimization, assessment and proposed use of a direct nested reverse transcription-polymerase chain reaction protocol for the detection of hepatitis C virus. J Hum Virol 1(1):58–65, 1997

    Google Scholar 

  16. Shindo M, Di Bisceglie Am, Biswas R, Mihalik K, Feinstone S: Hepatitis C virus replication during acute infection in the chimpanzee. JID 166:424–427, 1992

    Google Scholar 

  17. Dean RB, Dixon WJ: Simplified statistics for small number of observations. Anal Chem 23:636–638, 1951

    Google Scholar 

  18. Masotti L, Casali E, Galeotti T: Lipid peroxidation in tumour cells. Free Radic Biol Med 4:377–386, 1988

    Google Scholar 

  19. Vierucci A, Demartino M, Graziani E, Rossi ME, London WT, Blumberg BS: A mechanism for liver cell injury in viral hepatitis: Effects of hepatitis B virus on neutrophil function in vitro and in children with chronic active hepatitis. Pediatr Res 17(10):814–819, 1983

    Google Scholar 

  20. Hagen TM, Huang S, Curnutte J, Fowler P, Martinez V, When CM, Ames BN, Chisari FV: Extensive oxidative DNA damage in hepatocytes of transgenic mice with chronic active hepatitis destined to develop hepatocellular carcinoma. Proc Natl Acad Sci USA 91(26):12808–12812, 1994

    Google Scholar 

  21. Wood M, Dizdaroglu M, Gajewski E, Essigmann JM: Mechanistic studies of ionizing radiation of oxidative mutgenesis: genetic effects of a single 9-hydroxyguanine (7-hydro-8-oxoguanine) reside inserted at a unique site in a viral genome. Biochem 29:7024–7032, 1990

    Google Scholar 

  22. Kuchino Y, Mori F, Kasai H, Inoue H, Iwai S, Mitura K, Ohtsuka E, Nishimura S: Misreading of DNA templates containing 8-hydroxydeoxyguanosine at the modified base and at adjacent residues. Nature 327:77–79, 1987

    Google Scholar 

  23. DeMaria N, Colantoni A, Fagiuoli S, Liu GJ, Rogers BK, Farinati F, Van Thiel DH, Floyd RA: Association between reactive oxygen species and disease activity in chronic hepatitis C. Free Radic Biol Med 21(3):291–295, 1996

    Google Scholar 

  24. Houglum K, Venkataramini A, Lyche K, Chojkier M: A pilot study of the effects of d-α-tocopherol on hepatic stellate cell activation in chronic hepatitis C. Gastroenterology 113:1069–1073, 1997

    Google Scholar 

  25. Kew MC: Hepatic tumors and cysts. In Sleisenger & Fordtran' Gastrointestinal and Liver Disease: Pathology/Diagnosis/ Management. Volume 1, 6th ed. M Feldman, MH Sleisenger, BF Scharschmidt, (eds). Philadelphia, Saunders, 1998, PP 1364–1387

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schwarz, K.B., Kew, M., Klein, A. et al. Increased Hepatic Oxidative DNA Damage in Patients with Hepatocellular Carcinoma. Dig Dis Sci 46, 2173–2178 (2001). https://doi.org/10.1023/A:1011958814371

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1011958814371

Navigation