Nitrative DNA damage in human lung tissues in association with asbestos exposure

Abstract

Background Asbestos causes lung cancer and malignant mesothelioma. Chronic inflammation is considered to play a role in asbestos-induced carcinogenesis. Reactive oxygen/nitrogen species generated under inflammatory conditions may contribute to carcinogenesis by causing DNA damage. 8-Nitroguanine is a mutagenic DNA lesion formed during inflammation. In this study, we examined 8-nitroguanine formation in human lung tissues and the association with asbestos exposure. Methods We obtained autopsy and surgical specimens of non-tumor lung tissues of patients with malignant mesothelioma ( n = 15) and subjects without asbestos-associated diseases ( n = 21). Fiber contents (chrysotile, amphiboles and non-asbestos fibers) in tissues were analyzed by transmission electron microscopy. We performed immunohistochemistry to examine 8-nitroguanine formation in lung tissues, and analyzed the correlation of the staining intensity with fiber contents. This study was approved by the Ethics Committee of Mie University School of Medicine, Japan. Results The fiber contents of chrysotile and amphiboles in lung tissues were significantly larger in mesothelioma patients than in subjects without asbestos-associated diseases ( p p Conclusion These results suggest that the generation of reactive oxygen/nitrogen species and resulting DNA damage are largely accounted for by amphibole fibers. 8-Nitroguanine can be a potential biomarker to evaluate the asbestos exposure and predict carcinogenic risk.