[Frontiers in Bioscience 6, e12-22, April 1, 2001]

SIMIAN VIRUS 40 DETECTION IN HUMAN MESOTHELIOMA: RELIABILITY AND SIGNIFICANCE OF THE AVAILABLE MOLECULAR EVIDENCE

Bharat Jasani1, Christopher J Jones1, Corina Radu1, David Wynford-Thomas1, Hossein Navabi 2, Malcolm Mason 2, Malcolm Adams2 and Allen Gibbs 3

Departments of Pathology1, Oncology2 & Histopathology3, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, Wales, UK

TABLE OF CONTENTS

1. Abstract
2. Introduction
2.1. Early description of malignant mesothelioma
2.2. Discovery of link between asbestos exposure and malignant mesothelioma
2.3. Viral infection and malignant mesothelioma
3. Detection of simian virus 40 (SV40) in human tumours
3.1. SV40 and its accidental inoculation into the human population
3.2. Lack of pathogenic effects of inoculated SV40
3.3. Discovery of SV40-like DNA in human mesothelioma and other types of tumors
3.4. Epidemiological evidence
3.5. Reproducibility and reliability of SV40 DNA detection
3.6. Sensitivity of SV40 DNA detection
3.7. Incidence of SV40 DNA detection in human tumors
3.8. Specificity of SV40 DNA detection
4. Biological effects of expression of SV40 gene products in human tumors
4.1. Biological activity and physical state of SV40 DNA detected in human mesothelioma
4.2. Characteristics of SV40 DNA associated with human and animal tumors
4.3. Cellular evidence of SV40 activity in tumor cells
5. Perspective
6. References

1. ABSTRACT

Simian virus 40 was discovered as a contaminant of early poliovirus vaccines that were inadvertently administered to millions of people in Europe and the United States between 1955 and 1963. Although SV40 was proven to be oncogenic in rodents and capable of transforming human and animal cells in vitro, its role in human cancer could not be proven epidemiologically. The matter was forgotten until 1993 when SV40 was accidentally found to cause mesotheliomas in hamsters injected intra-cardially. Subsequently, DNA sequences associated with its powerful oncogenic principal, the large T antigen, were found with high frequency in human pleural mesothelioma using the polymerase chain reaction (PCR). Since then many laboratories have confirmed the human findings. However, a few laboratories have failed to reproduce these data and the authors of the studies have claimed that the detection of SV40 DNA may simply represent PCR contamination artefacts. The controversy raised by this viewpoint is reviewed in this article together with a critical appraisal of the reliability of the molecular techniques used to detect SV40 DNA, in order to evaluate the potential aetiopathogenic role of SV40 in human mesothelioma.