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

Toxicol Lett. 2020 Oct 15;333:140-149. doi: 10.1016/j.toxlet.2020.07.033. Epub 2020 Aug 2.

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.

Keywords: C-FOS; C-JUN; Chrysotile; Oncogenic potential; P16; P53.

MeSH terms

  • Animals
  • Asbestos, Serpentine / chemistry
  • Asbestos, Serpentine / toxicity*
  • Bronchoalveolar Lavage Fluid / cytology
  • China
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • Cytokines / metabolism
  • Environmental Pollutants / chemistry
  • Environmental Pollutants / toxicity*
  • Gene Expression / drug effects
  • Inhalation Exposure / adverse effects
  • JNK Mitogen-Activated Protein Kinases / genetics
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Leukocyte Count
  • Leukocytes / cytology
  • Leukocytes / drug effects
  • Lung / drug effects*
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Mineral Fibers / toxicity
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Rats, Wistar
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Asbestos, Serpentine
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cytokines
  • Environmental Pollutants
  • Mineral Fibers
  • Proto-Oncogene Proteins c-fos
  • Tumor Suppressor Protein p53
  • JNK Mitogen-Activated Protein Kinases