Enhancement and Suppression of Murine Sarcoma Virus Induced Tumors by Polyriboinosinic Polyribocytidylic Acid

Gazdar, Adi F.; Weinstein, Allan J.; Sims, Harvie L.; Steinberg, A D

doi:10.3181/00379727-139-36126

Cited by 12 publications

(4 citation statements)

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“…In contrast, the following substances inhibit primary tumorigenesis: BCG in the MSV-mouse (Schwartz et al, 1971;Houchens et al, 1973), polyoma-hamster and -mouse (Lemonde and Clode-Hyde, 1966), and adenovirus-mouse systems; Freund's complete adjuvant in the adenovirus-mouse system ; thymosin in the MSV-mouse system (Zisblatt et al, 1970); polyribonucleotides (Sarma et al, 1969;Gazdar et al, 1972a;De Clercq and Stewart, 1974) and interferon (Berman, 1970) in the MSV-mouse system; clam liver extract in the adenovirus 12-hamster system (Li et ai., 1972); lipid-restim in the RSV-chicken system (Bliznakov, 1968); rifampicin (Toolan and Ledinko, 1972) and methotrexate (Li et ai., 1972) in the adenovirus-hamster system; cyclophosphamide in the MSV-mouse system, and estrone in the SV40-hamster system (Ohtaki, 1978). Endotoxin (Strausser and Bober, 1972) inhibited the growth of MSV mouse tumors; cyclophosphamide and retinoic acid stimulated CRA activity (Glaser, 1979c) and enhanced activity of the Winn test (Glaser, 1979d;Glaser and Lotan, 1979) in the SV40-mouse system.…”

Section: The Primary In Vivo Systemsmentioning

confidence: 99%

Immunopathology

1983

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Section: The Primary In Vivo Systemsmentioning

confidence: 99%

Immunopathology

1983

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“…Previous studies demonstrated that pretreatment with several interferon inducers of widely differing chemical composition and origin enhanced oncogenesis by RNA leukemia and sarcoma viruses (11). Tumor enhancement by rI*rC was not related to its adjuvant-like effects on humoral immunity, and was independent of the induced circulating interferon levels (6,10). Our present studies, demonstrating enhancement of the in vitro effects of MSV by polynucleo- tide pretreatment, provide further evidence that tumor enhancement cannot be mediated solely via in vivo operative mechanisms such as the immune system.…”

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confidence: 98%

“…Suppression of MSV oncogenesis by high doses of or continuous treatment with rI-rC may be mediated by a direct toxic or chemotherapeutic effect of the drug on the host and/or the tumor cell (10).…”

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confidence: 99%

Synthetic RNA and DNA Polynucleotides: in Vivo and in Vitro Enhancement of Oncogenesis by a Murine Sarcoma Virus

Gazdar

Ikawa

1972

Experimental Biology and Medicine

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The Moloney strain of murine sarcoma virus (MSV) rapidly induces tumors at the site of virus inoculation in mice of all ages and, at appropriate dilutions, induces discrete foci of transformed cells in mouse tissue culture cells ( 1, 2 ) . High doses of, or continuous treatment with interferon and interferon inducers can suppress MSV tumor induction and focus formation (3-6). However, recent studies demonstrate the highly complex nature of the role of interferon inducers in viral oncogenesis (7-1 1). Depending on the conditions, several interferon inducers are capable of either enhancing or suppressing MSV tumor induction ( 11 ) . We herein report the in vivo and in vitro enhancement of oncogenesis by MSV by several synthetic polyribo-and polydeoxyribonucleotides.Materials and Methods. Mice. Weanling AL/N mice were obtained from the Rabbit and Rodent Section, Division of Research Services, National Institutes of Health, Bethesda, Md.Virus. MSV concentrate was prepared from virus-induced tumors by differential centrifugation (12) and was a 1 g of tumor11 ml of virus equivalent. A single pool was used for the in vivo studies. The virus stock used for focus assays was prepared by superinfecting S+L-cells (13) with Moloney leukemia virus.Animal inoculati0.n. MSV was injected by the subcutaneous-intramuscular route. A dose that induces small tumors in approximately 60% of weanling mice was used (approximately 1 O3 focus-forming units). Mice were examined 4, 5 , 7,9,12,15, 20, 25, and 30 days after virus inoculation and tumor size was carefully graded 0-4+, using the criteria .

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“…Interferon inducers such as pyran copolymer, statolon, endotoxin, polyriboinosinic polyribocytidylic acid (poly [I] * poly [C ]), and Newcastle disease virus (NDV) have been shown to stimulate host resistance to viral infections (4) and nonviral infections: e.g., bacterial infections with Escherichia coli, Listeria monocytogenes, and Klebsiella pneumoniae (10,23,24,25,30), and protozoal infections with Plasmodium berghei, Toxoplasma gondii, and Leishmania donovani (11,14,22,27). In some conditions, however, the interferon inducer poly(I) poly(C) enhanced the severity of viral (Moloney-sarcoma, radiation leukemia, and Friend leukemia [7,9,16,17]), bacterial (L. monocytogenes [25,26]), protozoal (Leishmania donovani and Trypanosoma cruzi [11,15,19]), and fungal (Candida albicans and C. immitis [32]) infections. The stimulatory effect of poly(I) poly(C) on these infections might reflect an increased toxicity of the double-stranded ribonucleic acid (RNA) in infected animals.…”

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Increased Toxicity of Double-Stranded Ribonucleic Acid in Virus-Infected Animals

1973

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Virus-infected mice were significantly more susceptible to the toxic effects of double-stranded ribonucleic acid (RNA) than uninfected mice. A dramatic increase in mortality was observed after injection of either synthetic (polyriboinosinic polyribocytidylic acid) or natural (mycophage) double-stranded RNA in mice infected with Newcastle disease virus (NDV) or vesicular stomatitis virus (VSV). With the exception of endotoxin, interferon inducers other than double-stranded RNA, such as tilorone-hydrochloride and chlorite-oxidized oxyamylose, did not show this increased toxicity in virus-infected animals. The increased susceptibility of virus-infected animals to the toxic effects of doublestranded RNA appears to be related to the levels of interferon induced by the virus infection, either systemically, in the blood stream (after inoculation of NDV), or locally, in the brain (after infection with VSV).

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Enhancement and Suppression of Murine Sarcoma Virus Induced Tumors by Polyriboinosinic Polyribocytidylic Acid

Cited by 12 publications

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Immunopathology

Immunopathology

Synthetic RNA and DNA Polynucleotides: in Vivo and in Vitro Enhancement of Oncogenesis by a Murine Sarcoma Virus

Increased Toxicity of Double-Stranded Ribonucleic Acid in Virus-Infected Animals

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