Springer, Encyclopedic Reference Of Cancer (2001) Ocr 7.0 Lotb.pdf

864 SV40
the overall incidence of cancer in cohorts injected
with contaminated poliovaccines was similar
to that of cohorts who had not been exposed
to SV40 contaminated poliovaccines.
In more recent investigations done by Carbone
(reviewed in 2) dealing with the association
of SV40 and mesotheliomas, the majority
of hamsters injected intracardially with SV40
developed pleural mesotheliomas. When hamsters
were injected with SV40 in the pleural
space, all of the animals developed mesotheliomas
within 3-6 months. Other investigations
demonstrated that only the SV40 wild type,
not small t-ag by itself, injected intracardially
or intrapleurally, caused the transformation
and subsequent formation of mesotheliomas.
Since asbestos is a known carcinogen that induces
mesotheliomas, animals that had asbestos
inhaled or injected into them also developed
mesotheliomas, but to a lesser extent
then the injection of just SV40.
These results prompted investigations into
the possibility that mesotheliomas in humans
could be attributed to SV40 infection directly
or with SV40 acting as a co-carcinogen with asbestos.
Mesothelioma samples studies in 1994
showed that 60% of the samples expressed
SV40-like DNA sequences in human pleural
mesotheliomas. Additional studies conducted
by Testa (reviewed in 2) showed that 83% of
mesothelioma samples tested positive for
SV40. The results of both investigations were
confirmed by a total of thirty independent laboratories.
The presence of SV40 in mesotheliomas
and SV40-like DNA sequences does not necessarily
confirm SV40 as the sole direct cause
of mesotheliomas. The large T-ag protein was
investigated to determine what effect it had specifically
on the tumor suppressing gene p53.
Polymerase chain reaction (PCR), immunohistochemistry,
RNA in situ hybridization and
Western blot experiments demonstrated that
the large T-ag protein was able to bind successfully
to the p53 and inactivate it in the mesothelioma
samples. In addition, later tests showed
that large T-ag was able to bind to other tumor
suppressor genes and cause a similar result to
the p53 inactivation. This was a key finding
since it demonstrated that the large T-ag interactions
with tumor suppressor genes could
have an effect in promoting the development
of mesothelioma tumors by allowing mesothelial
cells to become more susceptible to other
carcinogens, specifically asbestos. If taking
into consideration whether or not exposure
to asbestos is correlated with higher rates of
SV40 aided mesotheliomas, 60% of patients
that had been exposed to asbestos had SV40like
DNA sequences present in their tumors.
As of yet, no definitive and final conclusion
can be extrapolated from the results that would
suggest or refute a direct correlation between
SV40 contaminated poliovaccines and its direct
causal role in the development and manifestation
in human mesothelioma and other tumors.
Mesothelioma studies that tested Finnish samples
for presence of SV40-like DNA sequences
failed for SV40 detection. This raises the question
of whether or not the Finnish poliovaccines
were contaminated with SV40. Using epidemiologic
data in connection with laboratory investigational
results, a strong connection between
SV40 and mesotheliomas exists. Prior to 1970,
the occurrences of mesotheliomas was uncommon,
but since then the incidence rate has increased
significantly. The degree of contamination
with SV40 of the poliovaccine that a person
received is also a factor to consider in forming a
correlation between SV40 and mesothelioma; it
has been shown that SV40 carcinogenesis is
proportional to the dosage amount given to
the animal. More recently, a modified large
T-ag was used as a vaccine to protect animals
when a SV40 active large T-ag was injected into
the same animal, causing a potential for development
of therapeutic drugs to combat human
cancers associated with SV40.
References
1. Carbone M (1999) Simian Virus 40 and human
tumors: it is time to study mechanisms. Journal
of Cellular Biochemistry 76:189-193
2. Carbone M, Fisher S, Powers A, Pass HI, Rizzo P
(1999) New molecular and epidemiological issues
in mesothelioma: role of SV40. Journal of Cellular
Physiology 180:167-172
3. Fisher G, Weber L, Carbone M (1999) Cancer risk
associated with Simian Virus 40 contaminated
polio vaccine. Anticancer Research 19:2173-2180