Nitrative and oxidative DNA damage in oral lichen planus in relation to human oral carcinogenesis
Ponlatham Chaiyarit, Ning Ma, Yusuke Hiraku, Somchai Pinlaor, Puangrat Yongvanit, Darunee Jintakanon, Mariko Murata, Shinji Oikawa, Shosuke Kawanishi, Ponlatham Chaiyarit, Ning Ma, Yusuke Hiraku, Somchai Pinlaor, Puangrat Yongvanit, Darunee Jintakanon, Mariko Murata, Shinji Oikawa, Shosuke Kawanishi
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.
(Cancer Sci 2005; 96: 553 -559).
Source: PubMed