Nitrative and oxidative DNA damage as potential survival biomarkers for nasopharyngeal carcinoma

Abstract

Currently, there are no satisfactory biomarkers available to screen for nasopharyngeal carcinoma (NPC). Nitric oxide (NO), produced by inducible nitric oxide synthase (iNOS), has been suggested to cause nitrative and oxidative stress, leading to the accumulation of 8-nitroguanine (8-NitroG) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the subsequent transversion mutation of DNA. The aim of this study was to evaluate iNOS expression and the status of nitrative and oxidative stress in NPC. Fifty-nine cases of NPC and 39 cases of chronic nasopharyngitis were investigated to examine the expression of iNOS and the formation of 8-NitroG and 8-OHdG, using double-immunofluorescent staining. The statistical differences in immunoreactivities were analyzed using the Mann-Whitney test. Thirty-six patients from the 57 cases of NPC and 36 healthy controls were investigated to examine the level of serum 8-OHdG, using enzyme-linked immunosorbent assay (ELISA). The statistical differences were analyzed using a t test. Strong DNA lesions were observed in the cancer cells of NPC patients. All cases of NPC were positive for 8-NitroG and 8-OHdG, and 54 (94.7%) were positive for iNOS. NPC samples exhibited significantly more intense staining for 8-NitroG, 8-OHdG and iNOS than those of chronic nasopharyngitis (P < 0.05, respectively). The mean value of serum 8-OHdG in the 36 NPC patients was 0.538 ± 0.336 ng/ml compared to 0.069 ± 0.059 ng/ml for the healthy controls. The difference in the serum levels of 8-OHdG between the NPC patients and controls was statistically significant (P < 0.05). Our present findings suggest that pathological stimulation of nasopharyngeal tissue, caused by bacterial, viral or parasitic inflammation, may lead to nitrative and oxidative DNA lesions, caused by NO. This may contribute to the cause and development of NPC. Thus, 8-NitroG and 8-OHdG could be potential biomarkers for evaluating the risk of NPC. Better understanding of the molecular mechanisms underlying nitrative and oxidative DNA damage may provide clues to molecular targets for new approaches of NPC prevention.

8-Nitroguanine, a Potential Biomarker to Evaluate the Risk of Inflammation-Related Carcinogenesis

“…IL-6 was expressed mainly in inflammatory cells of nasopharyngeal tissues of EBV-infected patients. We also found that serum levels of 8-oxodG were significantly higher in NPC patients than control subjects (Huang et al, 2011). Collectively, these findings indicate that the nuclear accumulation of EGFR and activation of STAT3 by IL-6 play a key role in iNOS expression and resultant DNA damage, leading to EBV-related NPC.…”

“…Using biopsy and surgical specimens of nasopharyngeal tissues from NPC patients in southern China, we performed double immunofluorescent staining to examine the formation of 8-nitroguanine and 8-oxodG Huang et al, 2011). Intensive immunoreactivity of iNOS was detected in the cytoplasm of 8-nitroguanine-positive cancer cells.…”

Loss of SPARC in bladder cancer enhances carcinogenesis and progression

“…There is a causal link between oxidative stress and cancer, where ROS produced by transformed epithelial cells and activated stromal and inflammatory cells account for DNA damage and genomic instability (3,6,31,32) and further contribute to carcinogenesis. Hence, we assessed accumulation of superoxide anions by staining freshly frozen bladder sections with dihydroethidine (DHE), whose oxidation gives rise to the fluorescent derivative ethidene (31,33).…”

Nitrative and oxidative DNA damage in infection-related carcinogenesis in relation to cancer stem cells

“…8-Nitroguanine and 8-oxodG were formed in epithelial cells of EBV-positive patients with chronic nasopharyngitis, and their intensities were significantly stronger in cancer cells of NPC patients [57]. The serum level of 8-oxodG in NPC patients was significantly higher than control patients, suggesting the involvement of oxidative stress [58]. We confirmed EBV infection at the nasopharyngeal tissues by using in situ hybridization for EBV-encoded RNAs (EBERs).…”