Full text in pdf format

In vivo immunomodulation with poly (A)⁺ RNA against a murine Balb/3T3 fibrosarcoma transfected with a mutant Ha-ras-1 oncogene

Alaíde Gonçalves; Maria Isabel da Silva; Geraldo A.S. Passos Jr.

Laboratório de Genética, Departamento de Morfologia, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo. Via do Café s/n, 14040-904 Ribeirão Preto, SP, Brasil. Fax: 55.16.633-0999, E-mail: gadspjun@usp.br Send correspondence to G.A.S.P. Jr.

ABSTRACT

Balb-c mice injected subcutaneously with a mouse embryo-derived Balb/3T3 cell line transfected with a mutant form of the oncogene c-Ha-ras-1, developed a neoplastic mass, classified as fibrosarcoma, at the site of injection. The cytoplasmic RNA from the spleens of these tumor-bearing mice was prepared and further separated into poly(A)⁺ and poly(A)^- RNA fractions. These RNA preparations were separately injected into normal Balb-c mice. The total cytoplasmic RNA and the poly(A)⁺ RNA fraction were able to induce in vivo reactivity against a challenge with viable neoplastic cells. The Poly(A)^- RNA fraction had no effect, nor did the control RNA extracted from the spleens of normal Balb-c mice.

Keywords: immunomodulation; RNA; murine; fibrosarcoma; oncogene.

REFERENCES

Aviv, H. and Leder, P. (1972). Purification of biologically active globin messenger RNA by chromatography on oligo-thymidilic acid-cellulose. Proc. Natl. Acad. Sci. USA 69: 1408-1412.

Barbacid, M. (1987). ras Genes. Ann. Rev. Biochem. 56: 779-827.

Barbacid, M. (1988). Cellular oncogene activation. In: Immunology Series (Klein, G., ed.). Marcker Dekker, New York, pp. 121.

Bertolini, M.C. and De Lucca, F.L. (1986). In vitro effect of 18S immune RNA on macrophage resistance to Trypanosoma cruzi. Cell. Mol. Biol. 32: 167-171.

Bos, J.L. (1989). ras oncogenes in human cancer: a review. Cancer Res. 49: 4682-4689.

Bos, J.L., Fearon, E.R., Hamilton, S.R., Verlaan-de Vries, M., van Boom, J.H., van der Eb, A.J. and Vogelstein, B. (1987). Prevalence of ras gene mutations in human colorectal cancers. Nature 327: 293-297.

Chien, Y-h. and Davis, M.D. (1993). How a/ß T-cell receptors "see" peptide/MHC complexes. Immunology Today 14: 597-602.

Darnell Jr., J.E., Nevins, J.R. and Zeevi, M. (1982). The role of poly(A) in mammalian gene regulation. In: UCLA Symposia on Molecular and Cellular Biology (Ommaley, B.W., ed.). Academic Press, New York.

De Lucca, F.L., Bertolini, M.C. and Zini, M.N. (1982). In vitro transfer of reactivity to Trypanosoma cruzi antigens from rat cells to human cells with immune RNA. J. Infectious Dis. 145: 148-151.

Gedde-Dahl III, T., Fossum, B., Eriksen, J.A., Thorsby, E. and Gaudernack, G. (1993). T cell clones specific for p21 ras-derived peptides: characterization of their fine specificity and HLA restriction. Eur. J. Immunol. 23: 754-760.

Kovary, K., Armelin, M.C.S. and Armelin, H. (1989). Ha-ras-1 oncogene dosage differentially affects Balb/3T3 cell' growth factor requirement and tumorigenicity. Oncogene Research 4: 55-64.

Mendes, N.F., Peixinho, Z.F., Longo, I.M., Moura, N.C., Beck, C., Passos Jr., G.A.S. and De Lucca, F.L. (1986). Transfer of cell-mediated immunity to HIV antigens in vivo to a Cebus monkey and in vitro to human lymphocytes with xenogeneic immune RNA. Braz. J. Med. Biol. Res. 19: 747-751.

Passos Jr., G.A.S. (1991). Immunological memory for HIV-1 induced in rabbits by immune poly(A)⁺ RNA. Braz. J. Med. Biol. Res. 7: 711-715.

Passos Jr., G.A.S. and De Lucca, F.L. (1988). In vivo induction of immunological memory to human tumor extract with poly(A)-containing immune RNA. Cell. Mol. Biol. 34: 157-164.

Passos Jr., G.A.S. and De Lucca, F.L. (1991). RNA-mediated transfer of cellular immunity to a synthetic env antigen of the ( human immunodeficiency virus (HIV-1). Mol. Cell. Biochem. 108: 1-8.

Raulet, D.H. (1989). The structure, function and molecular genetics of the y/5 T-cell receptor. Ann. Rev. Immunol. 7: 175-207.

_,Ribeiro, R.A., De Lucca, F.L., Flores, C.A., Cunha, F.Q. and Ferreira, S.H. (1993). RNA from LPS-stimulated macrophages induces the release of tumor necrosis factor a and interleukin-1 by resident macrophages. Mediators of Inflamation 2: 435-442.

Richie, J.P., Steele Jr., G.D., Wilson, R.E., Ervin, T., Wang, B.S. and Mannick, J.A. (1984). Current treatment of metastatic renal cell carcinoma with xenogeneic immune ribonucleic acid. J. Urol. 131: 236-238.

Sambrook, J., Fritsch, E.F. and Maniatis, T. (1989). Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, pp. 7.3-7.84.

Shi-Shan, L., Chang Fu, L., Fu-Ying, H. and Chang-Xue, Z. (1982). Preparation and clinical use of HBsAg immune RNA. Lancet 1: 197-198.

Shih, C. and Weinberg, R.A. (1982). Isolation of a transforming sequence from a human bladder carcinoma cell line. Cell 29: 161-169.

Steele Jr., G., Wang, B.S. and Mannick, J.A. (1982). Immune RNA and transfer factor. In: Immunological Approaches to Cancer Therapeutics (Mihich, E., ed.). John Wiley and Sons, Inc., New York, pp. 229-241.

White, B.N. and De Lucca, F.L. (1977). Preparation and analysis of RNA. In: Analytical Biochemistry of Insects (Turner, R.B., ed.). Elsevier-Scientific, Amsterdam, pp. 85-130.

Williams, A.F. and Barclay, A.N. (1988). The immunoglobulin superfamily-domains for cell surface recognition. Ann. Rev. Immunol. 6: 381-405.