Lipid Peroxidation, Antioxidative Defense and Level of 8-Hydroxy-2-Deoxyguanosine in Cervical Cancer Patients

Open access


Oxidative stress has been associated with cervical cancer. Our aim was to examine lipid peroxidation and the extent of oxidative stress in women diagnosed with different stages of cervical cancer in order to evaluate its potential role in the evolution of cancer. We measured the concentration of thiobarbituric acid reactive substances, activities of antioxidative enzymes and 8-hydroxy-2-deoxyguanosine in 153 subjects. Enzymatic activity as well as TBARS concentration were measured spectrophotometrically, while 8-OHdG was determined by gas chromatography-mass spectrometry. PPatients were categorized: group II H-SIL; group III FIGO Ia-Ib and group IV FIGO IIa-IV. Our results showed highly significant increase in the level of lipid peroxidation in group IV when com pared to the control group, group II and group III (p<0.001). Activity of superoxide dismutase was also significantly higher in group IV when compared to control group (p<0.01), group II (p<0.01) and group III (p<0.05). Activity of catalase was also significantly higher in group IV when compared to control group (p<0.005), group II (p<0.005) and group III (p<0.05). Activity of glutathione-S-transferase was also significantly higher in group IV when compared to control group (p<0.05), group II (p<0.05) and group III (p<0.05). Activities of glutathione peroxidase and glutathione reductase showed no significant differences among the groups. Level of 8-OHdG was significantly higher in group IV than in the other groups (p<0.01). It can be concluded that oxidative stress is possibly involved in the pathogenesis of cervical cancer, demonstrated by increased lipid peroxidation and an altered antioxidant defense system and higher levels of 8-OHdG.

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61(2): 69-90.

2. Jiang B, Xiao S, Khan MA, Xue M. Defective antioxidant systems in cervical cancer. Tumour Biol 2013; 34(4): 2003-9.

3. Notani PN. Global variation in cancer incidence and mortality. Curr Sci 2001; 81(5): 465-74.

4. Sgambato A, Zannoni GF, Faraglia B, Camerini A, Tar - quini E, Spada D, et al. Decreased expression of the CDK in hibitor p27Kip1 and increased oxidative DNA damage in the multistep process of cervical carcinogenesis. Gy - necol Oncol 2004; 92(3): 776-83.

5. Rice-Evans C, Burdon R. Free radical-lipid interactions and their pathological consequences. Prog Lipid Res 1993; 32(1): 71-110.

6. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007; 39(1): 44-84.

7. Gutteridge JM, Halliwell B. Antioxidants: Molecules, me - dicines, and myths. Biochem Biophys Res Commun 2010; 393(4): 561-4.

8. Ozderin OY, Akpinar MY, Topcuoglu C, Kayaçetin E. The role of oxidative stress in the etiopathogenesis of gluten-sensitive enteropathy disease. J Med Biochem 2017; 36: 243-50.

9. Kolanjiappan K, Manoharan S, Kayalvizhi M. Measure - ment of erythrocyte lipids, lipid peroxidation, antioxidants and osmotic fragility in cervical cancer patients. Clin Chim Acta 2002; 326(1): 143-9.

10. Chiou JF, Hu ML. Elevated lipid peroxidation and disturbed antioxidant enzyme activities in plasma and eryth - rocytes of patients with uterine cervicitis and myoma. Clin Biochem 1999; 32(3): 189-92.

11. Nakabeppu Y, Sakumi K, Sakamoto K, Tsuchimoto D, Tsuzuki T, Nakatsu Y. Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids. Biol Chem 2006. p. 373.

12. McCord JM, Fridovich I. Superoxide dismutase. An en - zymic function for erythrocuprein (hemocuprein). J Biol Chem 1969; 244(22): 6049-55.

13. Aebi H. Catalase in vitro. Methods Enzymol 1984; 105: 121-6.

14. Weissman SM. Red Cell Metabolism. A Manual of Bio - chemical Methods. 2nd Edition. Yale J Biol Med 1976; 49(3): 310-1.

15. Draper HH, Hadley M. Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 1990; 186: 421-31.

16. Grace Nirmala J, Narendhirakannan RT. Detection and genotyping of high-risk HPV and evaluation of anti-oxidant status in cervical carcinoma patients in Tamil Nadu State, India--a case control study. Asian Pac J Cancer Prev 2011; 12(10): 2689-95.

17. Manju V, Kalaivani Sailaja J, Nalini N. Circulating lipid peroxidation and antioxidant status in cervical cancer patients: a case-control study. Clin Biochem 2002; 35(8): 621-5.

18. Kim SY, Kim JW, Ko YS, Koo JE, Chung HY, Lee-Kim YC. Changes in Lipid Peroxidation and Antioxidant Trace Ele - ments in Serum of Women With Cervical Intra epithelial Neoplasia and Invasive Cancer. Nutr Cancer 2003; 47(2): 126-30.

19. Bhuvarahamurthy V, Balasubramanian N, Govindasamy S. Effect of radiotherapy and chemoradiotherapy on circulating antioxidant system of human uterine cervical carcinoma. Mol Cell Biochem 1996; 158(1): 17-23.

20. Balasubramaniyan N, Subramanian S, Govindasamy S. Status of antioxidant systems in human carcinoma of uterine cervix. Cancer Lett 1994; 87(2): 187-92.

21. Beevi SS, Rasheed MH, Geetha A. Evidence of oxidative and nitrosative stress in patients with cervical squamous cell carcinoma. Clin Chim Acta 2007; 375(1-2): 119-23.

22. Lee GJ, Chung HW, Lee KH, Ahn HS. Antioxidant Vita - mins and Lipid Peroxidation in Patients with Cervical Intraepithelial Neoplasia. J Korean Med Sci 2005; 20(2): 267-72.

23. Sharma A, Rajappa M, Satyam A, Sharma M. Oxidant/ anti-oxidant dynamics in patients with advanced cervical cancer: correlation with treatment response. Mol Cell Biochem 2010; 341(1): 65-72.

24. Hristozov D, Gadjeva V, Vlaykova T, Dimitrov G. Evaluation of oxidative stress in patients with cancer. Arch Physiol Biochem 2001; 109(4): 331-6.

25. Demirci S, Ozsaran Z, Celik HA, Aras AB, Aydin HH. The interaction between antioxidant status and cervical cancer: a case control study. Tumori 2011; 97(3): 290-5.

26. Srivastava S, Natu SM, Gupta A, Pal KA, Singh U, Agarwal GG, et al. Lipid peroxidation and antioxidants in different stages of cervical cancer: Prognostic significance. Indian J Cancer 2009; 46(4): 297-302.

27. Manoharan S, Kolanjiappan K, Kayalvizhi M. Enhanced lipid peroxidation and impaired enzymic antioxidant activities in the erythrocytes of patients with cervical carcinoma. Cell Mol Biol Lett 2004; 9(4a): 699-707.

28. Kumaraguruparan R, Subapriya R, Viswanathan P, Nagini S. Tissue lipid peroxidation and antioxidant status in patients with adenocarcinoma of the breast. Clin Chim Acta 2002; 325(1-2): 165-70.

29. Chung-man Ho J, Zheng S, Comhair SA, Farver C, Erzu - rum SC. Differential expression of manganese superoxide dismutase and catalase in lung cancer. Cancer Res 2001; 61(23): 8578-85.

30. Wozniak B, Mila-Kierzenkowska C, Kedziora-Korna towska K, Drewa T, Drewa G, Wozniak A, et al. Influence of the management of cervical carcinoma on the activity of cata lase and glutathione peroxidase in erythrocytes. Eur J Gynaecol Oncol 2007; 28(6): 461-3.

31. Mila-Kierzenkowska C, Kedziora-Kornatowska K, Woz - niak A, Drewa T, Wozniak B, Drewa S, et al. The effect of brachytherapy on antioxidant status and lipid peroxidation in patients with cancer of the uterine cervix. Cell Mol Biol Lett 2004; 9(3): 511-8.

32. Sharma A, Rajappa M, Saxena A, Sharma M. Antioxidant status in advanced cervical cancer patients undergoing neoadjuvant chemoradiation. Br J Biomed Sci 2007; 64(1): 23-7.

33. Bhabak KP, Mugesh G. Functional mimics of glutathione peroxidase: bioinspired synthetic antioxidants. Acc Chem Res 2010; 43(11): 1408-19.

34. Sharma R, Yang Y, Sharma A, Awasthi S, Awasthi YC. Antioxidant role of glutathione S-transferases: protection against oxidant toxicity and regulation of stress-mediated apoptosis. Antioxid Redox Signal 2004; 6(2): 289-300.

35. Niitsu Y, Takahashi Y, Saito T, Hirata Y, Arisato N, Maru - yama H, et al. Serum glutathione-S-transferase-pi as a tumor marker for gastrointestinal malignancies. Cancer 1989; 63(2): 317-23.

36. di Ilio C, Sacchetta P, del Boccio G, la Rovere G, Federici G. Glutathione peroxidase, glutathione S-transferase and glutathione reductase activities in normal and neoplastic human breast tissue. Cancer Lett 1985; 29(1): 37-42.

37. Polidoro G, Di Ilio C, Sacchetta P, Del Boccio G, Federici G. Isoelectric focusing of brain cortex GSH S-transferase activity in mammals: evidence that polymorphism is absent in man. Int J Biochem 1984; 16(7): 741-6.

38. Terzi S, Dursun E, Yılmaz A, Cos¸kun ZÖ, Ozgur A, Celiker M, Demirci M. Oxidative stress and antioxidant status in patients with bell’s palsy. J Med Biochem 2017; 36; 18-22.

39. Romano G, Sgambato A, Mancini R, Capelli G, Giovag - noli MR, Flamini G, et al. 8-hydroxy-2 -deoxyguanosine in cervical cells: correlation with grade of dysplasia and human papillomavirus infection. Carcinogenesis 2000; 21(6): 1143-7.

40. Looi ML, Mohd Dali AZ, Md Ali SA, Wan Ngah WZ, Mohd Yusof YA. Oxidative damage and antioxidant status in patients with cervical intraepithelial neoplasia and carcinoma of the cervix. Eur J Cancer Prev 2008; 17(6): 555-60.

Journal of Medical Biochemistry

The Journal of Society of Medical Biochemists of Serbia

Journal Information

IMPACT FACTOR 2017: 1.378
5-year IMPACT FACTOR: 0.704

CiteScore 2017: 1.05

SCImago Journal Rank (SJR) 2017: 0.307
Source Normalized Impact per Paper (SNIP) 2017: 0.532


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 308 308 77
PDF Downloads 171 171 19