Mineral fibre toxicity: expression of retinoblastoma (Rb) and phospho-retinoblastoma (pRb) protein in alveolar epithelial and mesothelial cell lines exposed to fluoro-edenite fibres

Our plain-English summary of Mineral fibre toxicity: expression of retinoblastoma (Rb) and phospho-retinoblastoma (pRb) protein in alveolar epithelial and mesothelial cell lines exposed to fluoro-edenite fibres, by G. Musumeci, V. Cardile, C. Fenga, et al (Cell Biology and Toxicology, 2011).

The study

• Authors: G. Musumeci, V. Cardile, C. Fenga, S. Caggia, C. Loreto
• Journal: Cell Biology and Toxicology
• Published: 2011;27(3):217-25
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Several asbestos-like mineral fibres, including fluoro-edenite, may cause lung cancer and/or other lung diseases. However, biological and molecular mechanisms linked to cancer development after mineral fibre exposure have not been fully investigated. In the present study, human non-malignant mesothelial (MeT-5A) and human bronchoalveolar alveolar epithelial (A549) cell lines were incubated with rising concentrations of fluoro-edenite to evaluate the expression of retinoblastoma (Rb) protein, which has been demonstrated to play an important role in cell cycle control and tumour progression. Intriguingly, these results show that Rb expression was unchanged, while the level of the phosphorylated protein increased significantly in a dose-dependent manner, suggesting an involvement of this regulator protein in the pathogenesis of the lung diseases induced by mineral fibres. In conclusion, fluoro-edenite regulates the expression of phospho-retinoblastoma to trigger a network of signals strictly connected with cell proliferation and neoplastic cell transformation.

In plain English

This laboratory study exposed two kinds of human cells grown in culture to fluoro-edenite, an amphibole mineral fibre collected around Biancavilla, Sicily. One cell line (A549) came from a human bronchoalveolar carcinoma. The other (MeT-5A) was made of non-malignant transformed human pleural mesothelial cells. The cells were incubated for 48 hours with 10, 50 or 100 μg/ml of fibres. The authors then measured the retinoblastoma protein (Rb) and its phosphorylated form (pRb). At the lowest concentration, pRb was not significantly different from untreated cells. At 50 and 100 μg/ml, pRb rose significantly (p less than 0.05) in both cell lines, most strongly at 100 μg/ml. Total Rb did not change significantly. Cyclin D1 also rose at the two higher concentrations, and the authors reported a significant positive relationship between cyclin D1 and pRb. A protein called p27 fell in both cell lines. Cell viability decreased at all three concentrations. The authors concluded that the fibres had profound effects on the cells and activated several pathways related to carcinogenesis. They noted that Rb levels in these cell lines may not be representative.

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: in vitro laboratory experiment on human cell lines (Western blot, immunocytochemistry and MTT cell viability assay)
• Who was studied: Two human cell lines: A549, human bronchoalveolar carcinoma-derived cells (obtained from the American Type Culture Collection), and MeT-5A, non-malignant transformed human pleural mesothelial cells; no people or animals were studied
• Exposure: Fluoro-edenite fibres (the fraction labelled 'fluoro-edenite 19') collected around Biancavilla, Sicily. Average length 12 to 40 μm, average diameter 0.5 μm. Given at 10, 50 or 100 μg/ml for 48 hours (2,236, 11,180 and 22,360 × 10³ fibres/ml respectively).
• Main results:
  • At 10 μg/ml, pRb expression in exposed cells was not significantly different from control cultures
  • At 50 and 100 μg/ml, pRb was strongly (grade 3) and significantly (p less than 0.05) overexpressed in both A549 and MeT-5A cells, with the strongest expression at 100 μg/ml
  • Total Rb expression did not change significantly with fibre exposure (grade 1)
  • In samples with significantly different pRb expression, the ratio of pRb to total Rb always exceeded 50%
  • Cyclin D1 increased significantly in both A549 and MeT-5A cells after 48 hours at 50 and 100 μg/ml, but not at 10 μg/ml
  • A correlation plot showed a significant positive relationship between cyclin D1 and pRb expression
  • Fluoro-edenite reduced p27 expression in both cell lines
  • Viability of MeT-5A and A549 cells decreased at all fibre concentrations, most strongly at 100 μg/ml
• The authors' conclusion: The authors concluded that the fibres had profound effects on the cells and activated several pathways related to carcinogenesis
• Limitations the authors state:
  • The authors noted that Rb expression levels in A549 and MeT-5A cells may not be representative

Topics

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, fluoro-edenite, Lung Cancer.

Related studies

• Immunohistochemical expression of retinoblastoma and phospho-retinoblastoma protein in sheep lung exposed to fluoro-edenite fibers — G. Musumeci, C. Loreto, et al. (2010)
• Effects of the new-identified amphibole fluoro-edenite in lung epithelial cells — S. Travaglione, B. Bruni, et al. (2003)
• Multinucleation and pro-inflammatory cytokine release promoted by fibrous fluoro-edenite in lung epithelial A549 cells — S. Travaglione, B.M. Bruni, et al. (2006)
• Fluoro-edenite fibers induce expression of Hsp70 and inflammatory response — V. Cardile, L. Lombardo, et al. (2007)
• N-acetylcysteine prevents cytotoxic effects induced by man-made mineral fibers in a human bronchial epithelial cell line — M. Zhang, H. Xia, et al. (2018)
• 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 — H.N. Kim, Y. Morimoto, et al. (2001)

Browse return to medical research.