Overexpression of inducible nitric oxide synthase and accumulation of 8-OHdG in nasopharyngeal carcinoma.
OBJECTIVE
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).


RESULTS
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).


CONCLUSIONS
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.
Segawa
Y
Y
Department of Anatomic Pathology, and Department of Otolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Oda
Y
Y
Yamamoto
H
H
Uryu
H
H
Shiratsuchi
H
H
Hirakawa
N
N
Tomita
K
K
Yamamoto
T
T
Oda
S
S
Yamada
T
T
Komune
S
S
Tsuneyoshi
M
M
D000080242:8-Hydroxy-2'-Deoxyguanosine; D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003598:Cytoskeletal Proteins; D004249:DNA Damage / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D060588:LIM Domain Proteins; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D018307:Neoplasms, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C484380:PDLIM7 protein, human; D012333:RNA, Messenger; D012367:RNA, Viral; D016159:Tumor Suppressor Protein p53; D000080242:8-Hydroxy-2'-Deoxyguanosine; D052247:Nitric Oxide Synthase Type II; D003849:Deoxyguanosine