Formation of the nitrative DNA lesion 8-nitroguanine is associated with asbestos contents in human lung tissues: a pilot study

Our plain-English summary of Formation of the nitrative DNA lesion 8-nitroguanine is associated with asbestos contents in human lung tissues: a pilot study, by Y. Hiraku, K. Sakai, E. Shibata, et al (Journal of Occupational Health, 2014).

The study

• Authors: Y. Hiraku, K. Sakai, E. Shibata, M. Kamijima, N. Hisanaga, N. Ma, S. Kawanishi, M. Murata
• Journal: Journal of Occupational Health
• Published: 2014;56(3):186-96
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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.

In plain English

This pilot study asked whether a kind of DNA damage called 8-nitroguanine (8-nitroG), which forms during inflammation, is linked to the amount of asbestos in human lungs. The authors examined non-tumor lung tissue collected at 16 hospitals from 1980 to 2008 from 15 patients with malignant mesothelioma and 20 people (21 specimens) without it. They counted asbestos fibers (chrysotile and amphiboles) by electron microscopy and scored DNA damage by tissue staining. Mesothelioma patients had more asbestos in their lungs. Among people without mesothelioma, 8-nitroG staining was correlated with total asbestos (R=0.560) and amphibole content (R=0.534), but not with chrysotile. Among mesothelioma patients, staining was not correlated with asbestos content. In people without mesothelioma, another DNA lesion, 8-oxodG, was correlated with age and with duration of occupational asbestos exposure, but not with asbestos content. The authors noted that the comparison group included people with lung diseases such as pneumonia and fibrosis, which may have affected staining. They concluded that 8-nitroG may possibly serve as a biomarker of asbestos exposure and cancer risk.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective pilot study of archived human lung tissue, using tissue staining (immunohistochemistry) to score DNA damage and analytical transmission electron microscopy to count fibers
• Who was studied: 36 non-tumor lung tissue specimens from autopsy and surgical material, taken at 16 hospitals from 1980 to 2008. The specimens came from 15 patients with malignant mesothelioma (9 males and 6 females, mean age 60.7) and from 20 subjects (21 specimens) without mesothelioma (11 males and 9 females, mean age 66.3). The study was approved by an ethics committee in Japan.
• Exposure: Lung content of asbestos (chrysotile and amphiboles) and non-asbestos fibers per gram of dry lung, measured for all fibers and for fibers 1 µm or longer. Duration of occupational asbestos exposure was also examined.
• Main results:
  • Total asbestos content was significantly larger in mesothelioma patients than in subjects without mesothelioma. The geometric means were 13.45 ± 5.27 versus 1.94 ± 2.76, in units of ×10^6 fibers per gram of dry lung, with p less than 0.001.
  • There was no significant difference in staining intensities between the two groups, although 8-nitroG staining tended to be slightly higher in mesothelioma patients.
  • When all cases were analyzed together, staining intensity was not correlated with any type of inorganic fiber.
  • In subjects without mesothelioma, 8-nitroG staining was significantly correlated with total asbestos content (R=0.560, p=0.008) and with amphibole content (R=0.534, p=0.013).
  • In subjects without mesothelioma, staining of the repair enzyme APE1 was significantly correlated with total asbestos content (R=0.582, p=0.006).
  • In subjects without mesothelioma, counting only fibers 1 µm or longer gave a stronger correlation between 8-nitroG staining and total asbestos content (R=0.652, p=0.001).
  • In subjects without mesothelioma, staining of these molecules was not significantly correlated with chrysotile or non-asbestos fiber content.
  • In mesothelioma patients, staining of DNA lesions and repair enzymes was not correlated with asbestos content in the lung.
  • In subjects without mesothelioma, stepwise regression found that amphibole content was the only independent variable influencing 8-nitroG staining (R2=0.247, p=0.013).
  • 8-oxodG staining was correlated with duration of occupational asbestos exposure, both in all cases (R=0.487, p=0.003) and in subjects without mesothelioma (R=0.675, p=0.001).
  • In subjects without mesothelioma, 8-oxodG staining was correlated with age (R=0.535, p=0.012).
  • 8-oxodG staining was not significantly correlated with asbestos content.
• The authors' conclusion: The authors concluded that their findings raise a possibility that 8-nitroG could serve as a potential biomarker to evaluate asbestos exposure and carcinogenic risk.
• Limitations the authors state:
  • DNA damage was mainly evaluated in bronchial and alveolar epithelial cells. Some specimens did not contain enough mesothelial cells for evaluation.
  • The group without mesothelioma included cases of lung diseases such as pneumonia and fibrosis. The authors could not exclude that tissue changes such as inflammation influenced the staining results.

Topics

Medical terms in this study, explained in our Lexicon: 8-Nitroguanine, Lung Cancer, Malignant Mesothelioma, Chronic Inflammation, Carcinogenesis, Biomarker, Carcinogenic, Inflammation.

Related studies

• Crosstalk between DNA Damage and Inflammation in the Multiple Steps of Carcinogenesis — S. Kawanishi, S. Ohnishi, et al. (2017)
• Role of nitrative and oxidative DNA damage in inflammation-related carcinogenesis — M. Murata, R. Thanan, et al. (2012)
• Detection of 8-oxo-2'-deoxyguanosine, a marker of oxidative DNA damage, in culture medium from human mesothelial cells exposed to crocidolite asbestos — Q. Chen, J. Marsh, et al. (1996)
• Phosphorylation of p53 protein in A549 human pulmonary epithelial cells exposed to asbestos fibers — M. Matsuoka, H. Igisu, et al. (2003)
• The role of iNOS-mediated DNA damage in infection- and asbestos-induced carcinogenesis — Y. Hiraku, S. Kawanishi, et al. (2010)
• Iron associated with asbestos bodies is responsible for the formation of single strand breaks in phi X174 RFI DNA — L.G. Lund, M.G. Williams, et al. (1994)

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