Nitrative and oxidative DNA damage in oral lichen planus in relation to human oral carcinogenesis.

Abstract

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.

• Authors: Ponlatham Chaiyarit, Ning Ma, Yusuke Hiraku, Somchai Pinlaor, Puangrat Yongvanit, Darunee Jintakanon, Mariko Murata, Shinji Oikawa, Shosuke Kawanishi
• Journal: Cancer science (Cancer Sci) Vol. 96 Issue 9 Pg. 553-9 (Sep 2005) ISSN: 1347-9032 [Print] England
• PMID: 16128740 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (Cancer Sci 2005; 96: 553 -559).

Chemical References

• 8-nitroguanine
• Deoxyadenosines
• Mutagens
• Tumor Suppressor Protein p53
• Guanine
• 2'-deoxy-7,8-dihydro-8-oxoadenosine
• Nitric Oxide Synthase

Topics

• Adult
• Aged
• Aged, 80 and over
• Biopsy
• Carcinoma, Squamous Cell (physiopathology)
• DNA Damage
• Deoxyadenosines (pharmacokinetics, toxicity)
• Female
• Fluorescent Antibody Technique
• Guanine (analogs & derivatives, pharmacokinetics, toxicity)
• Humans
• Immunohistochemistry
• Lichen Planus, Oral (complications, etiology, physiopathology)
• Male
• Middle Aged
• Mouth Mucosa (pathology)
• Mouth Neoplasms (physiopathology)
• Mutagens (toxicity)
• Nitric Oxide Synthase (biosynthesis, physiology)
• Tumor Suppressor Protein p53 (metabolism, pharmacokinetics)