Journal of occupational health · 2014
Formation of the nitrative DNA lesion 8-nitroguanine is associated with asbestos contents in human lung tissues: a pilot study.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Hiraku Yusuke, Sakai Kiyoshi, Shibata Eiji, Kamijima Michihiro, Hisanaga Naomi, Ma Ning, Kawanishi Shosuke, Murata Mariko
Аннотация
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.
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.