Formation of the Nitrative DNA Lesion 8‐Nitroguanine is Associated with Asbestos Contents in Human Lung Tissues: A Pilot Study

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  • Hiraku Yusuke
    Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine
  • Sakai Kiyoshi
    Nagoya City Public Health Research Institute
  • Shibata Eiji
    Department of Health and Psychosocial Medicine, Aichi Medical University School of Medicine
  • Kamijima Michihiro
    Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences
  • Hisanaga Naomi
    Center for Campus Health and Environment, Aichi University of Education
  • Ma Ning
    Faculty of Health Science, Suzuka University of Medical Science
  • Kawanishi Shosuke
    Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science
  • Murata Mariko
    Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine

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  • Formation of the Nitrative DNA Lesion 8-Nitroguanine is Associated with Asbestos Contents in Human Lung Tissues: A Pilot Study

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Objectives: Asbestos causes lung cancer and malignant mesothelioma, and chronic inflammation is considered to participate in carcinogenesis. However, biomarkers to evaluate its carcinogenic risk have not been established. Reactive oxygen/nitrogen species are generated in biological systems under inflammatory conditions and may contribute to carcinogenesis by causing DNA damage. In this study, we examined the relationship between the formation of 8-nitroguanine (8-nitroG), a mutagenic DNA lesion formed during inflammation, and asbestos contents in human lung tissues. Methods: We obtained non-tumor lung tissues from patients with (n=15) and without mesothelioma (n=21). The expression of 8-nitroG and related molecules was examined by immunohistochemistry, and their staining intensities were semiquantitatively evaluated. Asbestos contents in lung tissues were analyzed by analytical transmission electron microscopy. Results: In subjects without mesothelioma, staining intensities of 8-nitroG and apurinic/apyrimidinic endonuclease 1 (APE1) were significantly correlated with total asbestos and amphibole contents (p<0.05), but not with chrysotile content. In mesothelioma patients, their staining intensities were not correlated with asbestos contents. The double immunofluorescence technique revealed that APE1 was expressed in 8-nitroG-positive cells, suggesting that abasic sites were formed possibly due to the removal of 8-nitroG. The staining intensities of 8-oxo-7,8-dihydro-2′-deoxyguanosine, an oxidative DNA lesion, and its repair enzyme 8-oxoguanine DNA-glycosylase were correlated with age (p<0.05), but not with asbestos contents in subjects without mesothelioma. Conclusions: This is the first study to demonstrate that 8-nitroG formation is associated with asbestos contents in human lung tissues. This finding raises a possibility that 8-nitroG serves as a biomarker that can be used to evaluate asbestos exposure and carcinogenic risk.(J Occup Health 2014; 56: 186-196)

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