Comparison of 8-Hydroxy-Deoxyguanosine Levels in Cervical Cancer Advanced Stages Before and After Chemotherapy
DOI:
https://doi.org/10.61841/r2wdfq43Keywords:
8-hydroxy-deoxyguanosine, cervical cancer, advanced stagesAbstract
Cervical cancer is the most commonly diagnosed cancer and the third leading cause of death of women in poor and developing countries. 8-hydroxy-deoxyguanosine (8-OHdG) levels have been widely used as a biomarker of oxidative DNA damage, including cervical cancer. This study aims to compare levels of 8-hydroxy-deoxyguanosine (8-OHdG) as a marker of oxidative stress in advanced cervical cancer (FIGO stages) before and after chemotherapy. This prospective study involved 18 patients stage IIB, 8 patients stage IIIA, 9 patients stage IIIB, and 2 patients stage IIIC of cervical cancer. 8-OHdG levels were measured with the ELISA method. The mean level of 8-OHdG before chemotherapy in stage II was 8.14±9.14 ng/ml and in stage III 8.07±8.79 ng/ml, whereas the mean level of 8-OHdG after chemotherapy in stage II was 24.24±12.46 ng/ml and at stage III 24.67±13.85 ng/ml. 8-OHdG levels increased significantly (p<.05) in stages IIA, IIIA, and IIIB after chemotherapy. In contrast, 8-OHdG levels in stage IIIC were not significantly increased after chemotherapy. In addition, 8-OHdG levels were significantly different between SCC and adenocarcinoma. Likewise, the type of differentiation is good, moderate, and non-classification. 8-OHdG levels increase significantly in advanced stages of cervical cancer after chemotherapy.
Downloads
References
1. Torre LA, Bray F, Siegel L, et al. Global Cancer Statistics 2012. Ca Cancer J Clin 2015;65:87–108.
2. Forman D, de Martel C, Lacey CJ, et al. Global burden of human papillomavirus and related diseases.
Vaccine 2012;30:F12-F23.
3. Woodman CBJ, Collins SI, Young LS: The natural history of cervical HPV infection: unresolved issues.
Nat Rev Cancer 2007;7:11-22.
4. zur Hausen H. Papillomaviruses in the causation of human cancers—a brief historical account. Virology
2009;384:260-5.
5. Klaunig JE, Kamendulis LM. The role of oxidative stress in carcinogenesis. Annu Rev Pharmacol
Toxocol 2004;44:29–67.
6. Kolanjiappan K, Manoharan S, Kayalvizhi M. Measurement of erythrocyte lipids, lipid peroxidation,
antioxidants and osmotic fragility in cervical cancer patients. Clin Chim Acta. 2002;326(1-2):143-9.
7. Looi ML, Mohd Dali AZ, Md Ali SA, et al. Oxidative damage and antioxidant status in patients with
cervical intraepithelial neoplasia and carcinoma of the cervix. Eur J Cancer Prev. 2008;17(6):555-560.
8. 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.
9. Gao CM, Takezaki T, Wu JZ, et al. Polymorphisms in thymidylate synthase and
methylenetetrahydrofolate reductase genes and the susceptibility to esophageal and stomach cancer with
smoking. Asian Pac J Cancer Prev. 2004;5(2):133-8.
10. Hwang ES, Bowen PE. DNA damage, a biomarker of carcinogenesis: Its measurement and modulation
by diet and environment. Crit Rev Food Sci Nutr 2007;47:27–50.
11. Ock CY, Kim EH, Choi DJ, et al. 8-Hydroxydeoxyguanosine: not mere biomarker for oxidative stres,
but remedy for oxidative stress-implicated gastrointestinal diseases. World J Gastroenterol.
2012;18(4):302-308.
12. Miyake H, Hara I, Kamidono S, Eto H. Oxidative DNA damage in patients with prostate cancer and its
response to treatment. J Urol. 2004;171:1533–36.
13. Weiss JM, Goode EL, Ladiges WC, Ulrich CM. Polymorphic variation in hOGG1 and risk of cancer: A review of the functional and epidemiologic literature. Mol Carcinog 2005;42:127–141.
14. Diakowska D, Lewandowski A, Kopec W, et al. Oxidative DNA damage and total antioxidant status in serum of patients with esophageal squamous cell carcinoma. Hepatogastroenterology 2007;54:1701–4.
15. Tanaka H, Fujita N, Sugimoto R, et al. Hepatic oxidative DNA damage is associated with increased risk
for hepatocellular carcinoma in chronic hepatitis C. Br J Cancer 2008;98:580–586.
16. Romano R, A Sgambato A, Mancini R, et al., 8-hydroxy-2'-deoxyguanosine in Cervical Cells:
Correlation With Grade of Dysplasia and Human Papillomavirus Infection. Carcinogenesis
2000;21(6):1143-1147.
17. Sgambato A, Zannoni GF, Faraglia B, et al. Decreased expression of the CDK in hibitor p27Kip1 and
increased oxidative DNA damage in the multistep process of cervical carcinogenesis. Gynecol Oncol
2004;92(3):776–83.
18. Jelić M, Mandić A, Kladar N, et al. Lipid peroxidation, antioxidative defense and level of 8-hydroxy-2-
deoxyguanosine in cervical cancer patients. J Med Biochem. 2018;37(3):336-345.
19. Cooke MS, Loft S, Olinski R. Measurement and meaning of oxidatively modified DNA lesions in urine.
CEBP 2008;17:3–14.
20. Pylväs-Eerola M, Karihtala P, Puistola U. Preoperative serum 8-hydroxydeoxyguanosine is associated
with chemoresistance and is a powerful prognostic factor in endometrioid-type epithelial ovarian cancer.
BMC Cancer. 2015;15:493.
21. Filippova M, Filippov V, Williams VM, et al. Cellular levels of oxidative stress affect the response of
cervical cancer cells to chemotherapeutic agents. Biomed Res Int. 2014;2014:574659.
22. Liu J, Wang Z. Increased oxidative stress as a selective anticancer therapy. Oxidative Med Cell Longev.
2015;2015:294303.
23. Leone A, Roca MS, Ciardiello C, et al. Oxidative stress gene expression profile correlates with cancer
patient poor prognosis: identification of crucial pathways might select novel therapeutic approaches.
Oxidative Med Cell Longev. 2017;2017:2597581.
24. Postovit L, Widmann C, Huang P, Gibson SB. Harnessing oxidative stress as an innovative target for
cancer therapy. Oxidative Med Cell Longev. 2018;2018:6135739.
25. Conklin KA. Chemotherapy-associated oxidative stress: impact on chemotherapeutic effectiveness.
Integr Cancer Ther 2004; 3: 294-300.
26. Wang J, Lin D, Peng H, et al. Cancer-derived immunoglobulin G promotes LPS-induced
proinflammatory cytokine production via binding to TLR4 in cervical cancer cells. Oncotarget
2014;5(20):9727–43.
27. Lovell MA, Gabbita P, Markesbery WR. Increased DNA oxidation and decreased levels of repair
products in Alzheimer’s disease ventricular CSF. J Neurochem 1999;72:771–776.
28. Hata I, Kaji M, Hirano S, et al. Urinary oxidative stres markers in young patients with type 1 diabetes.
Pediatr Int 2006;48:58–61.
29. Wong RH, Kuo CY, Hsu ML, et al. Increased levels of 8-hydroxy-20-deoxyguanosine attributable to
carcinogenic metal exposure among school children. Environ Health Perspect 2005;113:1386–1390.
30. Irie M, Tamae K, Iwamoto-Tanaka N, Kasai H. Occupational and lifestyle factors and urinary 8-
hydroxydeoxyguanosine. Cancer Sci. 2005;96:600–606.
31. Rodic S, Vincent DM, Reactive oxygen species (ROS) are key determinant of cancer’s metabolic phenotype. IJC. 2018 :440-448.
32. Mizutani H, Tada-Oikawa S, Hiraku Y, Kojima M, Kawanishi S. Mechanism of apoptosis induced by doxorubicin through the generation of hydrogen peroxide. Life Sci. 2005;76:1439–53.
33. Shi H, Shi X, Liu KJ. Oxidative mechanism of arsenic toxicity and carcinogenesis. Mol Cell Biochem.
2004;255:67–78.
34. Brozovic A, Ambriović-Ristov A, Osmak M. The relationship between cisplatin-induced reactive
oxygen species, glutathione, and BCL-2 and resistance to cisplatin. Crit Rev Toxicol. 2010;40(4):347–
359.
35. Raudenska M, Balvan J, Fojtu M, et al. Unexpected therapeutic effects of cisplatin. Metallomics.
2019;11(7):1182–1199.
36. Apel K, Hirt H. Reactive oxygen species: metabolism, oxidative stress, and signal transduction. Annu
Rev Plant Biol. 2004;55:373–99.
37. Yang H, Villani RM, Wang H, et al. The role of cellular reactive oxygen species in cancer
chemotherapy. J Exp Clin Cancer Res. 2018;37(1):266.
38. Maiti AK. Gene network analysis of oxidative stress-mediated drug sensitivity in resistant ovarian
carcinoma cells. Pharmacogenomics J. 2010;10:94–104.
39. Chou WC, Jie C, Kenedy AA, et al. Role of NADPH oxidase in arsenic-induced reactive oxygen species formation and cytotoxicity in myeloid leukemia cells. Proc Natl Acad Sci U S A. 2004;101:4578–83.
40. Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an irondependent form of nonapoptotic cell death. Cell. 2012;149:1060–72.
41. Sallmyr A, Fan J, Datta K, et al. Internal tandem duplication of FLT3 (FLT3/ITD) induces increased ROS production, DNA damage, and misrepair: implications for poor prognosis in AML. Blood. 2008;111:3173–82.
Downloads
Published
Issue
Section
License
Copyright (c) 2020 AUTHOR

This work is licensed under a Creative Commons Attribution 4.0 International License.
You are free to:
- Share — copy and redistribute the material in any medium or format for any purpose, even commercially.
- Adapt — remix, transform, and build upon the material for any purpose, even commercially.
- The licensor cannot revoke these freedoms as long as you follow the license terms.
Under the following terms:
- Attribution — You must give appropriate credit , provide a link to the license, and indicate if changes were made . You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
Notices:
You do not have to comply with the license for elements of the material in the public domain or where your use is permitted by an applicable exception or limitation .
No warranties are given. The license may not give you all of the permissions necessary for your intended use. For example, other rights such as publicity, privacy, or moral rights may limit how you use the material.