SV40 and the pathogenesis of mesothelioma

Our plain-English summary of SV40 and the pathogenesis of mesothelioma, by P. Rizzo, M. Bocchetta, A. Powers, et al (Seminars in Cancer Biology, 2001).

The study

• Authors: P. Rizzo, M. Bocchetta, A. Powers, R. Foddis, E. Stekala, H.I. Pass, M. Carbone
• Journal: Seminars in Cancer Biology
• Published: 2001;11(1):63-71
• Type of article: Review
• Cited by: 57 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma, a tumor of the pleura, pericardium, and peritoneum, is presently a worldwide problem. Current therapy is ineffective in slowing the course of the disease, and median survival from the time of diagnosis is rarely greater than 1 year. While the tumor was almost unknown prior to the second half of the twentieth century, it is presently responsible for more than 2000 deaths per year in the US alone. Mesothelioma is frequently associated with exposure to asbestos, but the incidence of cases involving individuals with low levels of asbestos exposure is increasing. For this reason, there has been much interest in studying whether there are alternative factors that act alone or in conjunction with asbestos in producing this malignancy. In the last decade, simian virus 40 (SV40) has become the most notable suspected agent.

Copyright 2001 Academic Press.

In plain English

This article was a review of evidence on whether simian virus 40 (SV40), a monkey virus that potentially contaminated polio vaccines given in the US from 1955 to 1963, plays a part in mesothelioma, alone or together with asbestos. The authors used the word asbestos to mean amphibole asbestos. They summarized hamster studies in which SV40 injected into the chest lining caused mesotheliomas in 100% of animals within 3 to 6 months. They also summarized human studies, including an initial one that found SV40 DNA in 29 of 48 mesotheliomas. SV40 was not found in Finnish mesotheliomas. They described their own laboratory work. In it, SV40 transformed human mesothelial cells at a rate more than 1000 times higher than fibroblasts. Crocidolite alone did not transform human cells in culture, but showed some co-carcinogenicity with SV40. The authors concluded that substantial evidence supports a role for SV40, while whether it causes human mesothelioma remains controversial. They noted that no epidemiological studies had compared mesothelioma rates in SV40-infected and uninfected people, and that many mesotheliomas are SV40-negative.

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: Narrative review, with a proposed working hypothesis about how SV40 and asbestos might interact
• Who was studied: Published animal studies (mainly hamsters), studies of human mesothelioma tissue samples, and the authors' own laboratory experiments on human mesothelial cells and fibroblasts
• Exposure: SV40 virus, including exposure through potentially contaminated poliovaccines (1955 to 1963), and asbestos, which the authors used to mean amphibole asbestos; crocidolite was used in the laboratory experiments
• Main results:
  • In cited hamster studies, injecting SV40 into the pleural space produced mesotheliomas in 100% of hamsters within 3 to 6 months
  • In an initial cited study of human tumors, SV40 sequences were found in 29 of 48 human mesotheliomas (60%)
  • SV40 was not detected in Finnish mesotheliomas; Finland has a very low incidence of mesothelioma and did not use SV40-contaminated poliovaccines
  • In the authors' earlier work on mesotheliomas, p53 was wild-type in 23 of 25 samples, and the SV40 large T antigen bound and stabilized p53
  • In the authors' laboratory experiments, the rate of transformation was more than 1000 times higher in human mesothelial cells infected with SV40 than in fibroblasts; all 16 of 16 transformed mesothelial clones could be established in tissue culture
  • In the authors' experiments, crocidolite alone failed to induce foci formation in human mesothelial cells and fibroblasts at all concentrations tested
  • In the same experiments, asbestos and SV40 showed some co-carcinogenicity: human fibroblasts given SV40 constructs plus crocidolite produced more foci than with SV40 alone
• The authors' conclusion: The authors concluded that there is substantial evidence supporting a role for SV40 in mesothelioma pathogenesis, but that several arguments against such a role remain and whether SV40 causes human mesothelioma is still controversial
• Limitations the authors state:
  • No epidemiological studies had compared mesothelioma incidence in SV40-infected and non-infected groups
  • Finding SV40 in human tumors does not by itself show that it caused them
  • Most mesotheliomas occur in asbestos-exposed people, and many mesotheliomas are SV40-negative
  • The amount of SV40 in mesothelioma is low, so detecting it requires very sensitive techniques
  • The rise in mesotheliomas after the contaminated vaccines were given also coincided with much more widespread asbestos use

Topics

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

Medical terms in this study, explained in our Lexicon: SV40, Mesothelioma, Malignant Mesothelioma, Pleura, Pericardium, Peritoneum, Median Survival, Asbestos Exposure.

Related studies

• New molecular and epidemiological issues in mesothelioma: role of SV40 — M. Carbone, S. Fisher, et al. (1999)
• Simian virus 40 is present in most United States human mesotheliomas, but it is rarely present in non-Hodgkin's lymphoma — P. Rizzo, M. Carbone, et al. (1999)
• Human mesotheliomas contain the simian virus-40 regulatory region and large tumor antigen DNA sequences — H.I. Pass, J.S. Donington, et al. (1998)
• Prospects for an SV40 vaccine — M.J. Imperiale, H.I. Pass, et al. (2001)
• Association of SV40 with human tumours — B. Jasani, A. Cristaudo, et al. (2001)
• Asbestos, Simian virus 40 and malignant mesothelioma — S.C. Stenton (1997)

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