Experimental Studies on Non-Asbestos Causes of Mesothelioma

The animal model experiments were carried out repeatedly in mice and also hamster to find out the potential of SV40 virus as the carcinogen as well as cocarcinogen, when evaluated in combination with asbestos, to trigger Malignant Mesothelioma. In short, the cocarcinogen studies, both in hamsters and mice, indicated that malignant mesothelioma did not develop in animals which are exposed to subcarcinogenic doses of the very virus, though a few hamsters developed lymphomas and sarcomas subsequent to a prolonged latency period.

Coexposure to SV40 as well as asbestos is believed to cause a dramatically higher incidence of malignant mesothelioma with significantly shorter tumor dormancy. The low amount of asbestos tried out were insufficient to trigger malignant mesothelioma. No cancerous tumors developed in the control group. In macroscopical context, most malignant mesothelioma tumors surrounded the lungs and/or pericardium or spread along peritoneum, and malignant mesothelioma nodules triggered both the peritoneal and pleural cavities. The histologic appearance of the malignant mesotheliomas were identical to that of human malignant mesothelioma. Most cases of mesothelioma in the coexposed groups indicated a sarcomatoid morphology or biphasic morphology.

Malignant mesothleiomas occurring in hamsters which are exposed to carcinogenic dose of crocidolite were mostly of epithelial trait, and the tumors displayed a more bland, well-differed, tubular papillary morphology. All tumors and the derived cell lines from SV40 alone as well as coexposed group, possessed SV40-specific DNA and tumor antigens.


The basis of cocarcinogenic interaction of the SV40 with asbestos has been studied further in in vitro cell culture system which uses primary human mesothelial cell lines.

In these studies, SV4 was found out to have a distinctive ability to emulate in a semi permissive mode in the human mesothelial cells, therefore leading to subcytolytic generation of this virus in a rather high proportion, reaching 80%, of the virally infected cells. By contrast, human fibroblasts all were found to undergo cell lysis and also death because of limited SV40 virion generation. Moreover, SV40, was found to protect the mesothelial cells against cytotoxic effects of asbestos added to cell culture system.

Eventually, SV40 and asbestos altogether caused higher frequency of cell transformation with some sort of substransforming units of the very virus. To attain these effects, SV40 relies on2 traits of oncogenic proteins: the massive T and small t antigens. The large one is capable of inducing numerical and structural chromosomal alter actions. Tag, in addition, induces insulin-growth development factor expression, inhibits p53 and pRb group of proteins, and generates c-met activity so as to trigger cell proliferation. The small t antigen (tag) inhibits cellular phosphatase 2A, causes MAP kinase and AP-1 activity to occur, and also works with Tag to bind as well as inhibit p53 and pRb.

From the experiments it is believed that the combined activity of tag and Tag antigens induce Notch-1 and telomerase activity, when acting in tandem with the potential mutagenic impacts of asbestos fibers which are closely apposed to or affected into the mesothelial cells, which results in the malignant transformation of the mesothelial cells, as examined in the in vitro and in vivo models of SV40-asbestos cocarcinogenic.


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