Crocidolite asbestos and SV40 are cocarcinogens in human mesothelial cells and in causing mesothelioma in hamsters

Barbara Kroczynska, Rochelle Cutrone, Maurizio Bocchetta, Haining Yang, Amira G. Elmishad, Pamela Vacek, Maria Ramos-Nino, Brooke T. Mossman, Harvey I. Pass, Michele Carbone*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

Abstract

Only a fraction of subjects exposed to asbestos develop malignant mesothelioma (MM), suggesting that additional factors may render some individuals more susceptible. We tested the hypothesis that asbestos and Simian virus (SV40) are cocarcinogens. Asbestos and SV40 in combination had a costimulatory effect in inducing ERK1/2 phosphorylation and activator protein-1 (AP-1) activity in both primary Syrian hamster mesothelial cells (SHM) and primary human mesothelial cells (HM). Ap-1 activity caused the expression and activation of matrix metalloprotease (MMP)-1 and MMP-9, which in turn led to cell invasion. Experiments using siRNA and chemical inhibitors confirmed the specificity of these results. The same effects were observed in HM and SHM. Experiments in hamsters showed strong cocarcinogenesis between asbestos and SV40: SV40 did not cause MM, asbestos caused MM in 20% of hamsters, and asbestos and SV40 together caused MM in 90% of hamsters. Significantly lower amounts of asbestos were sufficient to cause MM in animals infected with SV40. Our results indicate that mineral fibers and viruses can be cocarcinogens and suggest that lower amounts of asbestos may be sufficient to cause MM in individuals infected with SV40.

Original languageEnglish (US)
Pages (from-to)14128-14133
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number38
DOIs
StatePublished - Sep 19 2006

Keywords

  • Activator protein-1
  • ERK1/2
  • Environmental carcinogenesis
  • Matrix metalloprotease
  • Viral oncology

ASJC Scopus subject areas

  • General

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