Sarcoma viruses

In contrast to the effects obtained with viruses mentioned earlier, rous sarcoma virus (RSV) is inactivated by direct contact with 2 [81]. Evidence for the drug action by a chelate compound was obtained by using concentrations of 3a and copper(II) sulfate, neither of which individually affected enzyme activity or transforming abilities [82]. In a later study these workers showed that several metal complexes inhibit the RNA dependent DNA polymerases and the transforming ability of RSV, the most active compound being a 1 1 copper(II)... 

ROP Retinopathy of prematurity ROS Reactive oxygen species R-PIA R-(l-methyl-I-phenyltheyl)-adenosine RPMI 1640 Roswell Park Memorial Institute 1640 medium RS Reiter s syndrome RSV Rous sarcoma virus RTE Rabbit tubular epithelium RTE-a-5 Rat tubular epithelium ant n a-5... 

PMEA and its congeners are more effective in vivo than could be predicted from their in vitro potency. While less potent as an antiretrovirus agent than AZT in vitro, PMEA proved clearly superior to AZT when the two drugs were compared for their effectiveness in vivo, in mice infected with murine Moloney sarcoma virus [51,52]. PMEA was also shown to be effective against various other retrovirus infections, including Friend leukemia virus (FLV), Rauscher leukemia virus (RLV), and LP-BM5 (murine AIDS) virus infection in mice, feline leukemia virus (FeLV) or feline immunodeficiency virus (FIV) infection in cats, and SIV infection in macaque (rhesus) monkeys (for review, see Ref. 53). In the latter model [54], again PMEA proved far superior to AZT in suppressing several parameters of the disease. 

Balzarini J, Sobis H, Naesens L, Vandeputte M, De Clercq E. Inhibitory effects of 9-(2-phosphonylmethoxyethyl)adenine and 3 -azido-2, 3 -dideoxy-thymidinc on tumor development in mice inoculated intracerebrally with Moloney murine sarcoma virus. Int J Cancer 1990 45 486-489. 

Papkoff, J., Verma, I. M., and Hunter, T. (1982). Detection of a transforming gene product in cells transformed by Moloney murine sarcoma virus. Cell 29 417-426. 

Adenovirus transcription factor (ATF) is a protein activated by the adenovirus protein E2a and has turned out to be CREB (cAMP-responsive, element-binding protein) Jun is named for avian sarcoma virus 17 (I am told that junana is 17 in Japanese). 

FIGURE 8.13 Nonreceptor PTKs. These protein kinases form a large family, and most of them contain SH2 and SH3 domains. Several were originally discovered as transforming genes of a viral genome, hence names such as src or abl, derived from Rous sarcoma virus or Abelson murine leukemia virus, respectively. (Adapted from Hunter, T., Biochem. Soc. Trans., 24(2), 307-327, 1996.)... 

This enzyme is associated with the virions of RNA tumor viruses such as the Rous sarcoma virus (RSV). The enzyme has remarkable enzymatic activity in that it can catalyze several seemingly diverse steps in the synthesis of double-stranded DNA from the single-stranded RNA viral genome. The enzyme uses a tRNA for tryp-tophan as a primer to make a copy of DNA that is complementary to the viral RNA. The resulting RNA-DNA hybrid is converted to a double-stranded DNA molecule by ribon-uclease (RNase)H and DNA-dependent DNA polymerase activities that are intrinsic to reverse transcriptase. 

Simian sarcoma virus sis Growth factor, subunit of PDGF... 

Harvey murine sarcoma virus Ha-ras Guanine nucleotidebinding protein... 

Certain RNA viruses, particularly retroviruses, have also proven capable of inducing cancer. Retroviruses known to induce cancer in animals include Rous sarcoma virus, Kirsten murine... 

Fed diets containing 50 mg pure (99%) PCP/kg ortechnical grade (86%) for 10-12 weeks Mice exposed to technical-grade PCP had enhanced tumor susceptibility (1.9 times) from transplanted tumors mortality increased 2.4 times over controls after sarcoma virus inoculation. Mice exposed to pure PCP showed no enhanced growth of reduced tumors, but developed splenic tumors 22% vs. none in controls (Kerkvliet etal. 1982)... 

J. R. Glenney Jr. and D. Soppet. Sequence and expression of caveolin, a protein component of caveolae plasma membrane domains phosphorylated on tyrosine in Rous sarcoma virus-transformed fibroblasts. Proc. Natl. Acad. Sci. USA 89 10517— 10521 (1992). 

J. R. Glenney Jr. Tyrosine phosphorylation of a 22-kDa protein is correlated with transformation by Rous sarcoma virus. J. Biol. Chem. 264 20163-20166 (1989). 

Rein, A., J. Keller, A. M. Schultz, K. L. Holmes, R. Medicus, and J. N. Ihle. 1985. Infection of immune mast cells by Harvey sarcoma virus Immortalization without loss of requirement for interleukin-3. Mol Cell Biol 5(9) 2257-64. 

Sefton BM, Hunter T, Beemon K. 1980. Temperature-sensitive transformation by Rous sarcoma virus and temperature-sensitive protein kinase activity. J Virol 33 220-229. 

It is important to highlight that c-Src or cellular Src behaves as described above however there is a second form of Src termed v-Src or viral Src. v-Src was originally discovered as a component of the Rous Sarcoma virus, which causes cancer in chickens. The sequences of c-Src and v-Src are nearly identical. The major difference in the two proteins occurs in the C-terminal tail. While c-Src is regulated through phosphorylation of the C-terminus, v-Src has no C-terminal phosphorylation site and therefore is constitutively active and unregulated. 

Following identihcation of the Rous sarcoma virus, a substantial number of additional tumor-causing (oncogenic) viruses have been identified. We are left with the key question of how to reconcile two observations on the one hand, chemicals or chemical substances cause cancer, on the other hand, viruses cause cancer. These observations split the oncology community into two camps. As frequently happens in science, neither camp had the full story and the two opposing viewpoints proved to be entirely compatible. 

Each cell of the human body carries the potential to become cancerous in the form of its proto-oncogenes. The case of the src gene is far from unique. A great many proto-oncogenes have been discovered some of the best known are myc, myb, ras, fes, fins, fos, and jun (these names derive from the retrovirus in which they were discovered e.g., ras comes from a rat sarcoma virus and fes from a feline sarcoma virus). It follows that each of our cells harbors a number of protooncogenes, each of which may become activated and contribute to the formation of a tumor. 

The results from a study employing a human cell line showed that neither 5 nor 50 ppm petroleum-derived JP-5 (PD-JP5) interfered with Snyder-Theilen feline sarcoma virus (ST-FeSV)-directed transformation of human foreskin fibroblastic cells (Blakeslee et al. 1983). Higher concentrations ( 100 ppm) were cytotoxic. It was reported that marine diesel fuel failed to inhibit transformation in this assay, but data were not shown. The study authors consider this in vitro assay to be a useful predictor of carcinogenesis since several known carcinogens have been shown to suppress transformation in cells infected with the ST-FeSV virus by blocking a specific virus gene function (i.e., transformation) noncarcinogens do not inhibit virus-induced cell transformation in this test system. 

The concentration of toxin which causes a 50% reduction in cell bound dye after five days in culture. Cell lines used were H4TG, thioguanine-resistant rat hepatoma cells MDCK, Madin-Darb and canine kidney cells NIH3T3,NIH Swiss mouse embryo fibroblasts and KA31T, Kirsten strain of Moloney sarcoma virus-transformed 3T3 cells. 

Vedel, M., Lawrence, F., Robert-Gero, M. and Lederer, E. (1978) The antifungal antibiotic sinefungin as a very active inhibitor of mefhyltransferases and of the transformation of chick embryo fibroblasts by Rous sarcoma virus. Biochemical and Biophysical Research Communications, 85, 371-376. 

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