Changes in DNA 8-hydroxyguanine levels, 8-hydroxyguanine repair activity, and hOGG1 and hMTH1 mRNA expression in human lung alveolar epithelial cells induced by crocidolite asbestos

Our plain-English summary of Changes in DNA 8-hydroxyguanine levels, 8-hydroxyguanine repair activity, and hOGG1 and hMTH1 mRNA expression in human lung alveolar epithelial cells induced by crocidolite asbestos, by H.N. Kim, Y. Morimoto, T. Tsuda, et al (Carcinogenesis, 2001).

The study

• Authors: H.N. Kim, Y. Morimoto, T. Tsuda, Y. Ootsuyama, M. Hirohashi, T. Hirano, I. Tanaka, Y. Lim, I.G. Yun, H. Kasai
• Journal: Carcinogenesis
• Published: 2001;22(2):265-9
• Cited by: 81 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

We examined 8-hydroxyguanine (8-OH-Gua) formation and 8-OH-Gua repair enzyme activity in pulmonary type-II-like epithelial cells to determine whether oxidative stress induced by asbestos plays a role in its carcinogenic mechanism. A549 cells were incubated with crocidolite asbestos at concentrations of 0, 10, 50 and 100 microg/ml over 27 h. We then evaluated 8-OH-Gua formation, 8-OH-Gua repair enzyme activity and gene expression of 8-oxoguanine-DNA glycosylase 1 (hOGG1) and human MUtT homologue (hMTH1). This was done using a high-performance liquid chromatography system equipped with an electrochemical detector, endonuclease nicking assay and reverse transcription polymerase chain reaction, respectively. Crocidolite induced the formation of 8-OH-Gua in DNA at concentrations of 50 and 100 microg/ml. 8-OH-Gua levels increased at 9 h and had declined to near baseline at 27 h, whereas 8-OH-Gua repair enzyme activity peaked at 18 h post-crocidolite exposure. hOGG1 and hMTH1 mRNA levels were also increased by crocidolite exposure. These data suggest that crocidolite asbestos is associated with epithelial cell injury in the process of carcinogenesis through oxidative stress.

In plain English

This was a laboratory experiment on human lung cells, not a study of people. The authors exposed A549 cells, a human alveolar epithelial cell line originally derived from a person with alveolar cell carcinoma, to crocidolite asbestos. They measured three things: 8-hydroxyguanine (8-OH-Gua), a form of oxidative DNA damage; the activity of enzymes that repair it; and mRNA levels of the repair genes hOGG1 and hMTH1 and of the antioxidant enzyme Mn-SOD. After 18 hours, 8-OH-Gua was significantly higher than in unexposed cells at 50 and 100 µg/ml of crocidolite. At 100 µg/ml, 8-OH-Gua peaked at 9 hours, then fell back to control levels. Repair activity was 2-fold higher at 9 hours and 2.6-fold higher at its 18-hour peak. hOGG1 mRNA rose to 7.5-fold above control at 27 hours. hMTH1 mRNA rose up to 18 hours, then returned to control levels. Mn-SOD showed no significant change. The authors concluded that oxidative stress induced by crocidolite may play an essential role in lung cancer. They noted that repair activity measured in crude cell extracts could partly reflect other enzymes.

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: laboratory (in vitro) cell culture experiment
• Who was studied: A549 human alveolar epithelial cells, a cell line originally derived from an individual with alveolar cell carcinoma, purchased from American Type Cell Culture
• Exposure: UICC reference crocidolite asbestos at 0, 10, 50 and 100 µg/ml for 18 hours (dose-response), and at 100 µg/ml measured at 0, 9, 18 and 27 hours (time course)
• Main results:
  • After 18 hours, DNA 8-OH-Gua in crocidolite-treated cells was significantly higher than in control cells at 50 and 100 µg/ml
  • In cells exposed to 100 µg/ml, 8-OH-Gua peaked at 9 hours and then gradually decreased to control levels
  • 8-OH-Gua repair activity in exposed cells was 2-fold higher at 9 hours and 2.6-fold higher at 18 hours (its peak), and was still above control at 27 hours
  • hOGG1 mRNA in exposed cells rose in a time-dependent manner to 7.5-fold above control at 27 hours
  • hMTH1 mRNA in exposed cells increased up to 18 hours and then decreased to control levels at 27 hours
  • Mn-SOD mRNA in exposed cells showed no significant difference from control cells at any time point
• The authors' conclusion: The authors concluded that oxidative stress induced by crocidolite may play an essential role in lung cancer
• Limitations the authors state:
  • Repair enzyme activity measured in crude cell extracts could be due to other glycosylase/lyase enzymes that also recognize 8-OH-Gua

Topics

The National Library of Medicine indexes this study under subjects our site covers: Crocidolite.

Medical terms in this study, explained in our Lexicon: Crocidolite, Oxidative Stress, Carcinogenic, A549 Cells, Carcinogenesis.

Related studies

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• Crocidolite activates NF-kappa B and MIP-2 gene expression in rat alveolar epithelial cells. Role of mitochondrial-derived oxidants — K.E. Driscoll, J.M. Carter, et al. (1998)
• Crocidolite asbestos inhibits pentose phosphate oxidative pathway and glucose 6-phosphate dehydrogenase activity in human lung epithelial cells — C. Riganti, E. Aldieri, et al. (2002)
• Analysis of asbestos-induced gene expression changes in bronchiolar epithelial cells using laser capture microdissection and quantitative reverse transcriptase-polymerase chain reaction — C.B. Manning, B.T. Mossman, et al. (2006)
• mRNA expression patterns in different stages of asbestos-induced carcinogenesis in rats — H. Sandhu, W. Dehnen, et al. (2000)

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