Nitrative and oxidative DNA damage in oral lichen planus in relation to human oral carcinogenesis
Nitrative and oxidative DNA damage in oral lichen planus in relation to human oral carcinogenesis
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DOI：
10.1111/j.1349-7006.2005.00096.x
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发表时间：
2005-09-01
期刊：
影响因子：
5.7
通讯作者：
Kawanishi, S
中科院分区：
文献类型：
--
作者：
Chaiyarit, P;Ma, N;Kawanishi, S
口腔扁平苔藓（OLP）是一种慢性炎症性疾病，临床上与口腔癌的发展有关。一项双免疫荧光标记研究发现，8-硝基鸟嘌呤和8-氧代-7，8-二氢-2-脱氧鸟苷（8-oxodG）积累在口腔上皮中的OLP和口腔鳞状细胞癌（OSCC）活检标本，而很少或没有免疫反应性观察到在正常口腔粘膜。8-硝基鸟嘌呤和诱导型一氧化氮合酶（iNOS）在OLP和OSCC的口腔上皮中共定位。在口腔上皮细胞中也观察到了3-硝基酪氨酸的免疫反应性，并与8-硝基鸟嘌呤共定位，3-硝基酪氨酸由蛋白酪氨酸硝化形成，被认为是炎症的生化标志物。p53蛋白在口腔鳞状细胞癌中的表达明显高于口腔扁平苔藓，而在正常口腔粘膜中无p53蛋白表达。我们的研究结果表明，iNOS依赖的DNA损伤在OLP可能会导致p53的积累，不仅在OLP，但也OSCC。我们的结论是，形成潜在的致突变DNA损伤，包括8-硝基鸟嘌呤和8-oxodG可能有助于口腔癌的发展从OLP。
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.