Oxidative damage and antioxidant status in patients with cervical intraepithelial neoplasia and carcinoma of the cervix

Free radicals that induced lipid peroxidation and DNA damage have been implicated in many diseases including cancer. Cellular antioxidant defense plays an important role in neoplastic disease to counteract oxidative damage. This study aims to investigate the status of oxidative damage by measuring plasma malondialdehyde (MDA) level and urinary 8-hydroxydeoxyguanosine (8-OHdG), and the level of antioxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase in patients with cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC) of the cervix. Urinary 8-OHdG was measured by an enzyme-linked immunosorbent assay kit. MDA and antioxidant enzyme activities were determined by high-performance liquid chromatography and spectrophotometry, respectively. Eighty patients with CIN and SCC of the cervix were recruited and compared with normal controls. Urinary 8-OHdG/creatinine ratio did not show any significant changes in any disease status studied as compared with controls (P=0.803). Plasma MDA was found to be increased in CIN and SCC patients when compared with controls (P=0.002). Glutathione peroxidase activity was increased (P=0.0001) whereas superoxide dismutase and catalase activity was decreased (P=0.019 and 0.0001, respectively) in both CIN and SCC patients when compared with controls. Urinary 8-OHdG may not be a good marker for enhanced oxidative stress in cervical cancer. Oxidative damage as demonstrated by the level of MDA is markedly increased in CIN and SCC patients with changes of enzymatic antioxidants observed.

[1]  S. Toyokuni,et al.  Comparison between high-performance liquid chromatography and enzyme-linked immunosorbent assay for the determination of 8-hydroxy-2'-deoxyguanosine in human urine. , 2002, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[2]  J. Tainer,et al.  Active and inhibited human catalase structures: ligand and NADPH binding and catalytic mechanism. , 2000, Journal of molecular biology.

[3]  T. Takayama,et al.  Normalization of elevated hepatic 8-hydroxy-2'-deoxyguanosine levels in chronic hepatitis C patients by phlebotomy and low iron diet. , 2001, Cancer research.

[4]  C. Kuo,et al.  Increased Levels of 8-Hydroxy-2′-Deoxyguanosine Attributable to Carcinogenic Metal Exposure among Schoolchildren , 2005, Environmental health perspectives.

[5]  A. Junod,et al.  Role of oxygen free radicals in cancer development. , 1996, European journal of cancer.

[6]  S. Nam,et al.  Manganese Superoxide Dismutase Expression Correlates with a Poor Prognosis in Gastric Cancer , 2002, Pathobiology.

[7]  S. Batra,et al.  Lipid peroxidation, free radical production and antioxidant status in breast cancer , 2004, Breast Cancer Research and Treatment.

[8]  K. G. Akbulut,et al.  Daily variations of plasma malondialdehyde levels in patients with early breast cancer. , 2003, Cancer detection and prevention.

[9]  I. Sayek,et al.  Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients. , 2000, Clinical biochemistry.

[10]  J. Kalaivani Sailaja,et al.  Circulating lipid peroxidation and antioxidant status in cervical cancer patients: a case-control study. , 2002, Clinical biochemistry.

[11]  S. Hirohashi,et al.  Lung Cancer Patients Have Increased 8‐Hydroxydeoxyguanosine Levels in Peripheral Lung Tissue DNA , 1998, Japanese journal of cancer research : Gann.

[12]  J. Klaunig,et al.  The role of oxidative stress in carcinogenesis. , 2004, Annual review of pharmacology and toxicology.

[13]  S. Manoharan,et al.  Measurement of erythrocyte lipids, lipid peroxidation, antioxidants and osmotic fragility in cervical cancer patients. , 2002, Clinica chimica acta; international journal of clinical chemistry.

[14]  W. Dröge Free radicals in the physiological control of cell function. , 2002, Physiological reviews.

[15]  I. Fridovich,et al.  Assaying for superoxide dismutase activity: some large consequences of minor changes in conditions. , 1987, Analytical biochemistry.

[16]  İynem Alkan Hacer,et al.  The effect of prostate cancer and antianrogenic therapy on lipid peroxidation and antioxidant systems , 2004, International Urology and Nephrology.

[17]  Y. Mizushima,et al.  Changes in urinary levels of 8‐hydroxy‐2′‐deoxyguanosine due to aging and smoking , 2001 .

[18]  M. Mikhail,et al.  Plasma concentrations of coenzyme Q10 and tocopherols in cervical intraepithelial neoplasia and cervical cancer , 2003, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[19]  M. Nakayama,et al.  High iron storage levels are associated with increased DNA oxidative injury in patients on regular hemodialysis , 2005, Clinical and Experimental Nephrology.

[20]  L. Marnett,et al.  Oxyradicals and DNA damage. , 2000, Carcinogenesis.

[21]  M. Samir,et al.  Thiobarbituric acid reactive substances in patients with laryngeal cancer. , 1999, Clinical otolaryngology and allied sciences.

[22]  N. Kiviat,et al.  Dietary risk factors for invasive and in-situ cervical carcinomas in Bangkok, Thailand , 2002, Cancer Causes & Control.

[23]  W. Markesbery,et al.  Increased DNA Oxidation and Decreased Levels of Repair Products in Alzheimer's Disease Ventricular CSF , 1999, Journal of neurochemistry.

[24]  K. Tamae,et al.  Occupational and lifestyle factors and urinary 8‐hydroxydeoxyguanosine , 2005, Cancer science.

[25]  Gun-Hee Kim,et al.  Biomarkers for oxidative stress status of DNA, lipids, and proteins in vitro and in vivo cancer research. , 2007, Toxicology.

[26]  H. Tsukahara,et al.  Urinary oxidative stress markers in young patients with type 1 diabetes , 2006, Pediatrics international : official journal of the Japan Pediatric Society.

[27]  Tamotsu Inoue,et al.  Effect of Physical Exercise on the Content of 8‐Hydroxydeoxyguanosine in Nuclear DNA Prepared from Human Lymphocytes , 1993, Japanese journal of cancer research : Gann.

[28]  H. Bartsch,et al.  Oxidative stress and lipid peroxidation-derived DNA-lesions in inflammation driven carcinogenesis. , 2004, Cancer detection and prevention.

[29]  B. Halliwell Reactive oxygen species in living systems: source, biochemistry, and role in human disease. , 1991, The American journal of medicine.

[30]  A. Kural,et al.  The effect of prostate cancer and antiandrogenic therapy on lipid peroxidation and antioxidant systems. , 2004, International urology and nephrology.

[31]  L. Goya,et al.  Determination of malondialdehyde by liquid chromatography as the 2,4-dinitrophenylhydrazone derivative: a marker for oxidative stress in cell cultures of human hepatoma HepG2. , 2004, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[32]  S. Manoharan,et al.  Enhanced lipid peroxidation and impaired enzymic antioxidant activities in the erythrocytes of patients with cervical carcinoma. , 2004, Cellular & molecular biology letters.

[33]  W. Valentine,et al.  Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. , 1967, The Journal of laboratory and clinical medicine.

[34]  H. Aebi,et al.  Catalase in vitro. , 1984, Methods in enzymology.

[35]  N. Nalini,et al.  Evidence of oxidative stress in the circulation of ovarian cancer patients. , 2004, Clinica chimica acta; international journal of clinical chemistry.

[36]  P. Chang,et al.  Urinary 8-OHdG: a marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetics. , 2004, Clinica chimica acta; international journal of clinical chemistry.

[37]  S. Erzurum,et al.  Differential expression of manganese superoxide dismutase and catalase in lung cancer. , 2001, Cancer research.