Long-term instillation to four natural representative chrysotile of China induce the inactivation of P53 and P16 and the activation of C-JUN and C-FOS in the lung tissues of Wistar rats

Our plain-English summary of Long-term instillation to four natural representative chrysotile of China induce the inactivation of P53 and P16 and the activation of C-JUN and C-FOS in the lung tissues of Wistar rats, by Y. Luo, J. Deng, Y. Cui, et al (Toxicology Letters, 2020).

The study

• Authors: Y. Luo, J. Deng, Y. Cui, T. Li, J. Bai, L. Huang, Y. Sun, F. Dong, Q. Zhang
• Journal: Toxicology Letters
• Published: 2020;333:140-149
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Chrysotile is the only type of asbestos still widely exploited, and all kinds of asbestos including chrysotile was classified as a group I carcinogen by the IARC. There is a wealth of evidence that chrysotile can cause a range of cancers, including cancer of the lung, larynx, ovary, and mesothelioma. As the second largest chrysotile producer, China is at great risk of occupational exposure. Moreover, our previous experiment and some other studies have shown that the toxicity of mineral fibre from various mining areas may be different. To explore the oncogenic potential of chrysotile from different mining areas of China, Wistar rats were administered 0.5 mL chrysotile asbestos suspension of 2.0 mg/mL (from Akesai, Gansu; Mangnai, Qinghai; XinKang, Sichuan; and Shannan, Shaanxi) dissolved in saline by intratracheal instillation once-monthly and were sacrificed at 1 mo, 6 mo, and 12 mo. Our results found that chrysotile caused lung inflammation and lung tissue damage. Moreover, prolonged exposure of chrysotile can induce inactivation of the tumor suppressor gene P53 and P16 and activation of the protooncogene C-JUN and C-FOS both in the messenger RNA and protein level. In addition, chrysotile from Shannan and XinKang has a stronger effect which may link to cancer than that from Akesai and Mangnai.

Copyright © 2020 Elsevier B.V. All rights reserved.

In plain English

In this animal experiment, 90 male Wistar rats were divided into five groups of 18. Four groups had ground chrysotile asbestos from one of four Chinese mining areas (Akesai, Gansu; Mangnai, Qinghai; XinKang, Sichuan; Shannan, Shaanxi) placed directly into the windpipe once a month, as 0.5 mL of a 2.0 mg/mL suspension. A control group received saline. Rats were examined after 1, 6 and 12 months. At every time point, all chrysotile groups had more white blood cells than controls in fluid washed from the lungs, and higher lung levels of the inflammation markers IL-6, TNF-α and NF-κB. Messenger RNA for the tumor suppressor genes p53 and p16 rose at 1 month. It then fell below control levels at 6 and 12 months in the Mangnai, XinKang and Shannan groups. P53 protein was lower than in controls in all four chrysotile groups at 12 months. Messenger RNA for c-jun and c-fos rose in all chrysotile groups at 6 and 12 months. In these gene and protein measures, XinKang and Shannan chrysotile generally showed larger changes. The authors concluded that the effects may be related to inactivation of p53 and p16 and activation of c-jun and c-fos. They also noted that the overall results were "not relatively obvious."

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: Animal experiment: rats given repeated intratracheal instillation of chrysotile and compared with saline controls at 1, 6 and 12 months
• Who was studied: 90 ten-week-old specific pathogen-free male Wistar rats (180 to 200 g) from the Laboratory Animal Center of Southwest Medical University, China. They were randomly divided into five groups of 18: a negative control group and four chrysotile groups. Figure legends give n = 6 per measurement.
• Exposure: Natural chrysotile from four Chinese mining areas (Akesai, Gansu; Mangnai, Qinghai; XinKang, Sichuan; Shannan, Shaanxi), wet ball-milled to average particle sizes of 4.26, 4.76, 1.84 and 3.76 micrometres respectively. It was given as 0.5 mL of a 2.0 mg/mL saline suspension by intratracheal instillation once a month. Controls received 0.5 mL saline.
• Main results:
  • At all three exposure times, the number of white blood cells in lung lavage fluid was significantly higher in all chrysotile groups than in the negative control group (P < 0.05).
  • After 6 and 12 months, the inflammation markers IL-6, TNF-α and NF-κB in lung tissue were higher in all chrysotile groups than in controls (P < 0.05). The XinKang and Shannan groups were significantly higher than the Akesai and Mangnai groups.
  • After 6 and 12 months, the cell-damage markers LDH and AKP and total protein in lung lavage fluid were increased in all chrysotile groups compared with controls. The Mangnai and XinKang groups were significantly higher than the Akesai and Shannan groups.
  • At 1 month, p53 and p16 messenger RNA increased significantly in every chrysotile group compared with controls.
  • After 6 and 12 months, p53 and p16 messenger RNA in the Mangnai, XinKang and Shannan groups decreased significantly compared with controls. Levels in the XinKang and Shannan groups were lower than in the Akesai group (P < 0.05).
  • At 12 months, P53 protein was lower in all four chrysotile groups than in controls. It was significantly lower in the XinKang and Shannan groups than in the Akesai and Mangnai groups (P < 0.05).
  • P16 protein was higher than in controls in all four chrysotile groups at 1 month. After 6 and 12 months, it decreased significantly in the XinKang and Shannan groups compared with the control and Akesai groups (P < 0.05).
  • After 6 and 12 months, c-jun and c-fos messenger RNA increased significantly in all chrysotile groups. Levels in the Shannan and XinKang groups were significantly higher than in the Akesai and Mangnai groups (P < 0.05).
  • C-JUN and C-FOS proteins showed no difference between groups at 1 month. After 6 and 12 months, they were significantly higher in all chrysotile groups than in controls, except C-JUN protein in the Akesai group at 12 months.
• The authors' conclusion: The authors concluded that long-term instillation of natural chrysotile from the four mining areas could induce general lung injury and inflammatory responses in rat lung tissue. They concluded that the toxic effects may be related to inactivation of the tumor suppressor genes p53 and p16 and activation of the proto-oncogenes c-jun and c-fos. They also concluded that XinKang and Shannan chrysotile had more obvious effects on these cancer-related genes and proteins than Akesai and Mangnai chrysotile.
• Limitations the authors state:
  • Repeated intratracheal instillation was used, so the results cannot be directly compared with chronic inhalation and biopersistence experiments.
  • The authors stated that the overall results were not very pronounced, which they said suggests the toxicity of the four natural chrysotiles is not so strong. They suggested checking other cancer indicators in future work.
  • The authors stated that further experimental and multicenter epidemiological studies are needed.

Topics

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

Medical terms in this study, explained in our Lexicon: Chrysotile, IARC, Mesothelioma, Occupational Exposure, Inflammation, Tumor Suppressor Gene.

Related studies

• Oxidative effects of lungs in Wistar rats caused by long-term exposure to four kinds of China representative chrysotile — Y. Cui, Y. Zha, et al. (2019)
• Chrysotile effects on the expression of anti-oncogene P53 and P16 and oncogene C-jun and C-fos in Wistar rats' lung tissues — Y. Cui, Y. Wang, et al. (2018)
• Lung injury and expression of p53 and p16 in Wistar rats induced by respirable chrysotile fiber dust from four primary areas of China — Y. Zeng, Y. Cui, et al. (2018)
• Man-made mineral fiber effects on the expression of anti-oncogenes P53 and P16 and oncogenes C-JUN and C-FOS in the lung tissue of Wistar rats — Y. Cui, L. Huang, et al. (2019)
• Chrysotile and rock wool fibers induce chromosome aberrations and DNA damage in V79 lung fibroblast cells — Y. Cui, J. Ma, et al. (2018)
• A single intratracheal instillation of single-walled carbon nanotubes induced early lung fibrosis and subchronic tissue damage in mice — E.J. Park, J. Roh, et al. (2011)

Browse more research in Toxicology Letters, or return to medical research.