Simian virus 40 infection down-regulates the expression of nitric oxide synthase in human mesothelial cells

Our plain-English summary of Simian virus 40 infection down-regulates the expression of nitric oxide synthase in human mesothelial cells, by E. Aldieri, S. Orecchia, D. Ghigo, et al (Cancer Research, 2004).

The study

• Authors: E. Aldieri, S. Orecchia, D. Ghigo, L. Bergandi, C. Riganti, B. Fubini, P.G. Betta, A. Bosia
• Journal: Cancer Research
• Published: 2004;64(12):4082-4
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The cytotoxic effects of asbestos are partly mediated by the production of free radicals, including nitric oxide (NO). SV40 has been suggested to synergize with asbestos in the pathogenesis of malignant mesothelioma. Crocidolite asbestos fibers induced in human mesothelial and malignant mesothelioma cells a significant increase of NO synthase activity and expression, which was absent in SV40-infected cells. Furthermore, SV40 infection prevented the NF kappa B activation elicited by crocidolite in both mesothelial and mesothelioma cells. These data suggest that SV40, by inhibiting the synthesis of NO, could favor the survival of transformed, potentially neoplastic cells.

In plain English

This was a laboratory study of human cells grown in culture. The authors used normal mesothelial cells (cells lining the chest cavity) from the pleural fluid of three patients with congestive heart failure and no history of cancer. They also used malignant mesothelioma cells from the pleural fluid of three mesothelioma patients, one of them positive for simian virus 40 (SV40). Some normal cells were given SV40 DNA, or DNA for one SV40 protein called large tumor antigen. Cells were exposed to crocidolite asbestos fibers for 24 hours. In cells without SV40, crocidolite was followed by a significant rise in the activity of nitric oxide synthase, the enzyme that makes the free radical nitric oxide. Nitrite, a stable product of nitric oxide, also rose, as did messenger RNA for the inducible form of the enzyme. These rises did not occur in cells containing SV40. SV40 also prevented crocidolite's activation of NF-kappa B, a protein involved in switching on genes. The authors concluded that SV40, by inhibiting nitric oxide synthesis, could favor the survival of transformed, potentially cancerous cells.

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) experiment on cultured human mesothelial and malignant mesothelioma cells
• Who was studied: Primary cell cultures. Malignant mesothelioma cells came from the pleural effusions of three patients with histologically confirmed malignant mesothelioma, one of them SV40 positive. Normal human mesothelial cells came from three patients with transudative pleural fluid due to congestive heart failure and no history of malignant disease. Dates and patient locations are not stated.
• Exposure: Union International Contre le Cancer (UICC) crocidolite fibers, at the highest of three tested doses (printed as "25 g/cm2"), for 24 hours. About 45% of cells died under this condition. Some normal mesothelial cells were also transfected with full-length SV40 DNA or with a vector expressing the SV40 large tumor antigen (Tag).
• Main results:
  • After 24 hours with crocidolite, normal mesothelial cells and mesothelioma cells showed a significant increase in nitric oxide synthase activity inside the cells and in nitrite levels in the culture medium.
  • This increase was absent in normal mesothelial cells transfected with full-length SV40 or with large tumor antigen, and in the SV40-containing mesothelioma cells.
  • Crocidolite increased messenger RNA for inducible nitric oxide synthase (iNOS) in normal and mesothelioma cells. This effect was completely abolished in the presence of SV40.
  • SV40 infection prevented crocidolite-induced activation of NF-kappa B in both mesothelial and mesothelioma cells.
  • The level of the inhibitor protein I-kappa B in the cell cytoplasm was significantly reduced in crocidolite-treated cells, but not in cells containing SV40.
• The authors' conclusion: The authors concluded that SV40, by inhibiting the synthesis of nitric oxide, could favor the survival of transformed, potentially neoplastic cells.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, SV40, Malignant Mesothelioma, Crocidolite, Mesothelioma.

Related studies

• Regulation of nitric oxide synthase induction by iron and glutathione in asbestos-treated human lung epithelial cells — S.H. Park, A.E. Aust (1998)
• Expression of inducible nitric oxide synthase in healthy pleura and in malignant mesothelioma — Y. Soini, K. Kahlos, et al. (2000)
• Human mesothelial cells are unusually susceptible to simian virus 40-mediated transformation and asbestos cocarcinogenicity — M. Bocchetta, I. Di Resta, et al. (2000)
• Early inflammatory response to asbestos exposure in rat and hamster lungs: role of inducible nitric oxide synthase — M. Dörger, A.M. Allmeling, et al. (2002)
• Iron inhibits the nitric oxide synthesis elicited by asbestos in murine macrophages — E. Aldieri, D. Ghigo, et al. (2001)
• Endothelial nitric oxide synthase is strongly expressed in malignant mesothelioma but does not associate with vascular density or the expression of VEGF, FLK1 or FLT1 — Y. Soini, A. Puhakka, et al. (2001)

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