8-Nitroguanine formation in oral leukoplakia, a premalignant lesion
8-Nitroguanine formation in oral leukoplakia, a premalignant lesion
复制标题
DOI：
10.1016/j.niox.2005.09.012
复制
发表时间：
2006-03-01
影响因子：
3.9
通讯作者：
Kawanishi, S
中科院分区：
文献类型：
--
作者：
Ma, N;Tagawa, T;Kawanishi, S
口腔白斑是一种与口腔癌发展相关的癌前病变。为阐明口腔白斑癌变的机制，我们用免疫组织化学方法检测了口腔白斑活检标本口腔上皮细胞的DNA损伤。组织学变化。白斑患者口腔组织中可见上皮异型增生、炎性细胞浸润等。免疫荧光双标记法显示，在口腔白斑患者口腔粘膜上皮细胞中，亚硝化DNA损伤指标8-硝基鸟苷和DNA氧化损伤指标8-氧-7，8-二氢-2‘-脱氧鸟苷明显积聚，而正常口腔黏膜中几乎没有免疫反应。白斑患者口腔黏膜上皮中也有诱导型一氧化氮合酶(INOS)的表达。在口腔上皮细胞中观察到硝化应激指标3-硝基酪氨酸的免疫反应，并与8-硝基-鸟嘌呤共定位。基底层8-硝基鸟嘌呤阳性的上皮细胞表达增殖细胞核抗原和P53蛋白。这些结果表明，iNOS介导的硝化应激通过DNA损伤和氧化应激在口腔白斑癌变过程中起重要作用。(C)2005 Elsevier Inc.保留所有权利。
Oral leukoplakia is a premalignant lesion associated with development of oral cancer. To clarify the mechanism of development of oral carcinogenesis from leukoplakia, we examined DNA damage in oral epithelium of biopsy specimens of patients with leukoplakia by immunohistochemical methods. Histological changes,. such as epithelial dysplasia and infiltration of inflammatory cells were observed in oral tissues of leukoplakia patients. A double immunofluorescence labeling study demonstrated that the accumulation of mutagenic 8-nitroguanine, an indicator of nitrative DNA damage, and 8-oxo-7,8-dihydro-2'-deoxyguanosine, an indicator of oxidative DNA damage, was apparently observed in the oral epithelium of patients with leukoplakia, whereas little or no immuno reactivity was observed in normal oral mucosa. Expression of inducible nitric oxide synthase (iNOS) was also observed in oral epithelium of leukoplakia patients. Immunoreactivity of 3-nitrotyrosine, an indicator of nitrative stress, was observed in oral epithelial cells and colocalized with 8-nitroguanine. Moreover, proliferating cell nuclear antigen and p53 were expressed in 8-nitroguanine-positive epithelial cells in the basal layer. These results suggest that iNOS-mediated nitrative stress contributes to development of oral carcinogenesis from leukoplakia through DNA damage as well as oxidative stress. (c) 2005 Elsevier Inc. All rights reserved.