Salivary Nitric Oxide Levels and Buccal Epithelial Cell DNA Damage in Oral Cancer - A Biochemical Study
Background: Cancer is the one of the common cause of mortality in developed and developing countries. Tobacco in any form is found to induce cancer formation. Oral cancer is a multistage process with progressive changes occurring in genetic and cellular morphology as the disease progresses from the normal to premalignant state and then to malignant state. Recent studies have emphasised that nitric oxide is a highly reactive molecule that interacts with DNA resulting in DNA damage.The objective of the present study was to evaluate the nitric oxide levels in the saliva and buccal epithelial cell DNA damage in patients with oral cancer.
Material and methods: In this study nitric oxide levels in saliva and buccal epithelial cell DNA damage were estimated in 20 healthy individuals without oral lesions and 20 patients with oral cancer.
Results: The mean values of salivary nitric oxide levels were significantly greater in oral cancer patients (126.2155+/- 2.7587) when compared to that of controls (76.111+/-μM/L). Similarly the extent of DNA damage was higher in subjects with oral cancer (28.099+/- 1.2696) than in controls (9.15+/- 0.9131). Pearson's correlation between nitric oxide levels in saliva and extent of DNA damage were found to be moderately correlated in controlsr=0.491 (p<0.01) and in oral cancer patientsr=0.428 (p<0.01).
Conclusion: The results of present study illustrate an active involvement of nitric oxide which is derived from tobacco and its related products in the initiation of DNA damage and subsequent formation of oral cancer.
Received: 30 August 2016
Accepted: 08 January 2017
22 April 2020 (online)
Thieme Medical and Scientific Publishers Private Ltd.
A-12, Second Floor, Sector -2, NOIDA -201301, India
- 1 . Markopoulos AK. Current aspects on oral squamous cell carcinoma. Open Dent J 2012; 6:126-30.
- 2 Singh MP, Kumar V, Agarwal A, Kumar R, Bhatt MLB, Misra S. Clinicoepidemiological study of oral squamous cell carcinoma: A tertiary care centre study in North India. J Oral Biol and Craniofac Res. 2016;6:31-4.
- 3 Jain V, Dharkar D, Nandin H et al. Various addiction patterns and duration in head and neck carcinoma: an institutional experience from central India. Int J Health Sci Res. 2015; 5:130-35.
- 4 Bray, F, Ren, J-S, Masuyer, E, and Ferlay, J. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer. 2013; 132: 1133–1145.
- 5 Prasad G, McCullough M. Chemokines and cytokines as salivary biomarkers for the early diagnosis of oral cancer. Int J Dent 2013;2013:813756.
- 6 Palmer RMJ, Ferrige AG, Moncada S: Nitric oxide release accounts for the biological activity of endothelial-derived relaxing factor. Nature 1987;327:524–526.
- 7 Mocellin S, Bronte V, and Nitti D Nitric oxide, a double edged sword in cancer biology: searching for therapeutic opportunities. Medl Res Rev 2007; 27:317–352.
- 8 Bentz, B. G., Simmons, R. L., Haines, G. K., 3rd, &Radosevich, J. A. (). The yin and yang of nitric oxide: reflections on the physiology and pathophysiology of NO. Head Neck 2000;22: 71-83.
- 9 Ying L, Hofseth LJ: An emerging role for endothelial nitric oxide synthase in chronic inflammation and cancer. Cancer Res 2007, 67:1407–1410.
- 10 Jaiswal M., LaRusso, N. F., Burgart, L. J., & Gores, G. J. Inflammatory cytokines induce DNA damage and inhibit DNA repair in cholangiocarcinoma cells by a nitric oxide-dependent mechanism. Cancer Res, 2000;60: 184-190.
- 11 Wink, D. A., Hines, H. B., Cheng, R. Y., Switzer, C. H., Flores-Santana et al. Nitric oxide and redox mechanisms in the immune response. J LeukocBiol 2011; 89:873-91.
- 12 Fiddler RN. Collaborative study of modified AOAC method of analysis for nitrite in meat and meat products. J Assoc Of Anal Chem. 1977;60:594–599
- 13 Olive PL, Banáth JP. The comet assay: a method to measure DNA damage in individual cells. Nature protocols-electronic edition-. 2006 Jan 1;1(1):23.
- 14 Petersen EP et al. Oral cancer prevention &control the approach of the world health organization. Oral Oncology 2009; 45:454-460.
- 15 Korde SD, Basak A, Chaudhary M, Goyal M, Vagga A. Enhanced nitrosative and oxidative stress with decreased total antioxidant capacity in patients with oral precancer and oral squamous cell carcinoma. Oncology 2011;80(5–6):382–9.
- 16 Nair U, Bartsch H, Nair J. Alert for an epidemic of oral cancer due to use of the betel quid substitutes gutkha and pan masala: a review of agents and causative mechanisms. Mutagenesis 2004;19(4):251–62.
- 17 Ray G, Hussain SA. Oxidants ,anti oxidants and carcinogenesis.Indian J ExpBiol 2002;40:1213-32
- 18 Bahar G, Feinmesser R, Shpitzer T, Popovtze AR, Nagler RM. Salivary analysis in oral cancer patients DNA and protein oxidation, reactive nitrogen species, and antioxidant profile. Cancer 2007;109(1):54–9.
- 19 Patel JB, Shah FD, Shukla SN, Shah PM, Patel PS. Role of nitric oxide and antioxidant enzymes in the pathogenesis of oral cancer. JCRT 2009;5:247–53.
- 20 Li RH, Hotchkiss JH. Potential genotoxicity of chronically elevated nitric oxide: a review. Mutat Res 1995;339:73–89.
- 21 Saran R, Tiwari RK ,ReddyP P Risk assessment of oral cancer in patients with pre-cancerous states of the oral cavity using micronucleus test and challenge assay J oral oncol 2008;44;354-360.
- 22 Manikantan P , Balachandar V, Sasikala K Mohanadevi S et al Lymphocyte DNA Damage in Chewing Tobacco Users ofCoimbatore, Tamilnadu, by Using Comet Assay J Hum Ecol 2010; 31; 53-58 .
- 23 Mukherjee S, Ray JG, Chaudhuri K. Evaluation of DNA damage in oral precancerous and squamous cell carcinoma patients by single cell gel electrophoresis Indian J Dent Res. 2011;22(5):735-6.
- 24 Jyoti S et al Assessment of DNA damage by panmasala, gutkha chewing and smoking in buccal epithelial cells using alkaline single cell gel electrophoresis (SCGE). Egypt J Med Hum Genet 2013; 1: 1-4.