Nitrative and oxidative DNA damage in oral lichen planus in relation to human oral carcinogenesis.
Oral lichen planus (OLP) is a chronic inflammatory disease, which has been clinically associated with development to oral cancer. A double immunofluorescence labeling study found that 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) accumulated in oral epithelium in OLP and oral squamous cell carcinoma (OSCC) biopsy specimens, whereas little or no immunoreactivity was observed in normal oral mucosa. Colocalization of 8-nitroguanine and inducible nitric oxide synthase (iNOS) was found in oral epithelium of OLP and OSCC. Immunoreactivity of 3-nitrotyrosine, which is formed by protein tyrosine nitration and is considered to be a biochemical marker for inflammation, was also observed in oral epithelial cells and colocalized with 8-nitroguanine. Accumulation of p53 was more strongly observed in oral epithelium in OSCC than OLP, whereas there was no p53 accumulation in normal oral mucosa. Our findings demonstrate that iNOS-dependent DNA damage in OLP may lead to p53 accumulation in not only OLP but also OSCC. We conclude that the formation of potentially mutagenic DNA lesions including 8-nitroguanine and 8-oxodG may contribute to the development of oral cancer from OLP.
Chaiyarit
Ponlatham
P
Department of Oral Diagnosis, Faculty of Dentistry, Khon Kaen University, Khon Kaen, 40002, Thailand.
Ma
Ning
N
Hiraku
Yusuke
Y
Pinlaor
Somchai
S
Yongvanit
Puangrat
P
Jintakanon
Darunee
D
Murata
Mariko
M
Oikawa
Shinji
S
Kawanishi
Shosuke
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000503:physiopathology*; D004249:DNA Damage; D003839:Deoxyadenosines / Q000493:pharmacokinetics* / Q000633:toxicity; D005260:Female; D005455:Fluorescent Antibody Technique; D006147:Guanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D006801:Humans; D007150:Immunohistochemistry; D017676:Lichen Planus, Oral / Q000150:complications / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000503:physiopathology*; D009153:Mutagens / Q000633:toxicity; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism* / Q000493:pharmacokinetics
C095838:8-nitroguanine; D003839:Deoxyadenosines; D009153:Mutagens; D016159:Tumor Suppressor Protein p53; D006147:Guanine; C078251:2'-deoxy-7,8-dihydro-8-oxoadenosine; D019001:Nitric Oxide Synthase