The role of iNOS-mediated DNA damage in infection- and asbestos-induced carcinogenesis
The role of iNOS-mediated DNA damage in infection- and asbestos-induced carcinogenesis
复制标题
DOI：
10.1111/j.1749-6632.2010.05602.x
复制
发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Murata, Mariko
中科院分区：
文献类型：
--
作者：
Hiraku, Yusuke;Kawanishi, Shosuke;Murata, Mariko
慢性炎症是环境致癌的重要组成部分。各种传染病和物理、化学、免疫因素参与炎症相关癌变。在炎症条件下，炎症细胞和上皮细胞产生活性氧和活性氮，导致DNA损伤可能参与癌变。8-硝基鸟嘌呤是在慢性炎症中形成的一种致突变的DNA损伤。我们进行了免疫组织化学分析，证明在动物模型和由寄生虫、病毒和石棉暴露引起的各种易发癌症的感染性和炎症性疾病的患者中，8-硝基鸟嘌呤在癌变部位形成。在石棉暴露小鼠中，8-硝基鸟嘌呤在支气管上皮细胞中形成，值得注意的是，石棉比温石棉诱导的8-硝基鸟嘌呤形成明显更强烈，这与它们的致癌潜力不一致。基于这些发现，我们提出8-硝基鸟嘌呤可能是评估炎症相关癌变风险的潜在生物标志物。
Chronic inflammation contributes to a substantial part of environmental carcinogenesis. Various infectious diseases and physical, chemical, and immunological factors participate in inflammation-related carcinogenesis. Under inflammatory conditions, reactive oxygen and nitrogen species are generated from inflammatory and epithelial cells, and resulting DNA damage may participate in carcinogenesis. 8-Nitroguanine is a mutagenic DNA lesion formed during chronic inflammation. We performed immunohistochemical analysis, and demonstrated that 8-nitroguanine was formed at the sites of carcinogenesis in animal models and patients with various cancer-prone infectious and inflammatory diseases, caused by parasites, viruses, and asbestos exposure. In asbestos-exposed mice, 8-nitroguanine was formed in bronchial epithelial cells, and it is noteworthy that crocidolite induced significantly more intense 8-nitroguanine formation than chrysotile, inconsistent with their carcinogenic potentials. On the basis of these findings, we have proposed that 8-nitroguanine could be a potential biomarker to evaluate the risk of inflammation-related carcinogenesis.