8-hydroxy-2--deoxyguanosine and Nasopharyngeal-Neoplasms

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.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Chronic Disease; Deoxyguanosine; DNA Damage; DNA, Neoplasm; Enzyme-Linked Immunosorbent Assay; Female; Guanine; Humans; Immunoenzyme Techniques; Male; Middle Aged; Nasopharyngeal Neoplasms; Nasopharyngitis; Nasopharynx; Nitric Oxide Synthase Type II; Oxidation-Reduction; Oxidative Stress; Prognosis

Nitric oxide (NO), produced by inducible NO synthase (iNOS), has been suggested to cause oxidative stress, leading to 8-hydroxydeoxyguanosine (8-OHdG) accumulation and subsequent transversion mutation of DNA. The aim was to evaluate iNOS expression and the status of oxidative stress in nasopharyngeal carcinoma (NPC).. Seventy-three cases of NPC were investigated to examine the immunohistochemical expression of iNOS, 8-OHdG and latent membrane protein-1 (LMP-1) and Epstein-Barr virus-encoded small RNA (EBER) expression using in situ hybridization. iNOS mRNA expression and p53 gene mutations were also assessed. Overexpression of iNOS, LMP-1 and EBER was observed in 62 (84.9%), 28 (38.4%) and 53 (72.6%) cases respectively. p53 gene mutation was found in 10 of 73 (13.7%) cases. Immunohistochemical iNOS expression was associated with the 8-OHdG labelling index, iNOS mRNA expression and p53 gene alteration (P < 0.0001, P = 0.016 and 0.0082 respectively).. Our present findings suggest that the expression of iNOS induces oxidative stress in NPC. Although the presence of p53 mutation was associated with iNOS overexpression, the type of acid-base change of p53 was transition, but not transversion, which suggests that the p53 gene is not the direct target of DNA damage by 8-OHdG accumulation.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adaptor Proteins, Signal Transducing; Adult; Aged; Aged, 80 and over; Cytoskeletal Proteins; Deoxyguanosine; DNA Damage; DNA, Neoplasm; Female; Gene Expression Regulation, Neoplastic; Humans; Intracellular Signaling Peptides and Proteins; Kaplan-Meier Estimate; LIM Domain Proteins; Male; Middle Aged; Mutation; Nasopharyngeal Neoplasms; Neoplasms, Squamous Cell; Nitric Oxide Synthase Type II; Oxidative Stress; RNA, Messenger; RNA, Viral; Tumor Suppressor Protein p53