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. 1973 Apr;70(4):1250–1253. doi: 10.1073/pnas.70.4.1250

Continuous Propagation of Radiation Leukemia Virus on a C57BL Mouse-Embryo Fibroblast Line, with Attenuation of Leukemogenic Activity

Miriam Lieberman 1, Ohtsura Niwa 1, Alain Declève 1, Henry S Kaplan 1
PMCID: PMC433469  PMID: 4352226

Abstract

The radiation leukemia virus (RadLV), a murine leukemia virus derived from thymic lymphomas induced by x-irradiation in strain C57BL/Ka mice, has been successfully propagated in sustained high titer in vitro in a newly established line, BL-5, of C57BL/Ka mouse-embryo fibroblasts. In addition, the production of endogenous virus, presumed to be RadLV, has been induced and sustained through multiple serial passages after treatment of BL-5 cell cultures with 5-bromodeoxyuridine. The chronically RadLV-infected subline, designated BL-5 (RadLV), sheds virus into the supernatant culture fluids that is biologically active in vitro in the XC cell plaque assay, in interference assays for focus-formation by murine sarcoma virus, and in the intracellular induction of group-specific antigens detectable by immunofluorescence, but is apparently devoid of leukemogenic activity after intrathymic inoculation into neonatal or immunosuppressed C57BL/Ka mice. Although BL-5 cells exhibited morphological alterations suggestive of transformation in vitro and gave rise to fibrosarcomatous ascites tumors after intraperitoneal inoculation with C57BL/Ka mice, the chronically infected BL-5(RadLV) cells remained normal in morphology and failed to yield fibrosarcomas in vivo.

Keywords: murine leukemia virus, thymic lymphomas, 5-bromodeoxyuridine

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Declève A., Lieberman M., Hahn G. M., Kaplan H. S. Focus formation by a murine sarcoma leukemia virus complex. II. Quantitative aspects of the interaction between radiation leukemia virus and its murine sarcoma virus pseudotype in strain C57BL mouse embryo cells. J Virol. 1970 Apr;5(4):437–445. doi: 10.1128/jvi.5.4.437-445.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. FRIEND C. Cell-free transmission in adult Swiss mice of a disease having the character of a leukemia. J Exp Med. 1957 Apr 1;105(4):307–318. doi: 10.1084/jem.105.4.307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Fischinger P. J., O'Connor T. E. Radiation leukemia virus: quantitative tissue culture assay. Science. 1969 Jul 18;165(3890):306–309. doi: 10.1126/science.165.3890.306. [DOI] [PubMed] [Google Scholar]
  4. GINSBURG H., SACHS L. In vitro culture of a mammalian leukemia virus. Virology. 1961 Mar;13:380–382. doi: 10.1016/0042-6822(61)90165-9. [DOI] [PubMed] [Google Scholar]
  5. GROSS L. "Spontaneous" leukemia developing in C3H mice following inoculation in infancy, with AK-leukemic extracts, or AK-embrvos. Proc Soc Exp Biol Med. 1951 Jan;76(1):27–32. [PubMed] [Google Scholar]
  6. GROSS L. Attempt to recover filterable agent from x-ray induced leukemia. Acta Haematol. 1958 Jun;19(6):353–361. doi: 10.1159/000205455. [DOI] [PubMed] [Google Scholar]
  7. Gross L., Feldman D. G. Electron microscopic studies of radiation-induced leukemia in mice: virus release following total-body x-ray irradiation. Cancer Res. 1968 Sep;28(9):1677–1685. [PubMed] [Google Scholar]
  8. Hall W. T., Andresen W. F., Sanford K. K., Evans V. J., Hartley J. W. Virus particles and murine leukemia virus complement-fixing antigen in neoplastic and nonneoplastic cell lines. Science. 1967 Apr 7;156(3771):85–88. doi: 10.1126/science.156.3771.85. [DOI] [PubMed] [Google Scholar]
  9. Haran-Ghera N. Leukemogenic activity of centrifugates from irradiated mouse thymus and bone marrow. Int J Cancer. 1966 Jan;1(1):81–87. doi: 10.1002/ijc.2910010111. [DOI] [PubMed] [Google Scholar]
  10. Huebner R. J., Hartley J. W., Rowe W. P., Lane W. T., Capps W. I. Rescue of the defective genome of Moloney sarcoma virus from a noninfectious hamster tumor and the production of pseudotype sarcoma viruses with various murine leukemia viruses. Proc Natl Acad Sci U S A. 1966 Oct;56(4):1164–1169. doi: 10.1073/pnas.56.4.1164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Igel H., Huebner R. J., Deppa B., Bumgarner S. Rescue of the defective murine sarcoma virus genome by radiation-induced leukemia virus from C57BL mice. Proc Natl Acad Sci U S A. 1967 Nov;58(5):1870–1877. doi: 10.1073/pnas.58.5.1870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ioachim H. L., Berwich L., Furth J. Replication of gross leukemia virus in long-term cultures of rat thymomas: bioassays and electron microscopy. Cancer Res. 1966 May;26(5):803–811. [PubMed] [Google Scholar]
  13. Ioachim H. L., Berwick L. Continuous viral replication and cellular neoplastic transformation in cultures of normal rat thymus infected with gross leukemia virus. Int J Cancer. 1968 Jan 15;3(1):61–73. doi: 10.1002/ijc.2910030109. [DOI] [PubMed] [Google Scholar]
  14. Jasmin C., Chermann J. C., Mathé G., Raynaud M. Evidence of an inhibitor of Friend leukaemia. Rev Eur Etud Clin Biol. 1970 Jan;15(1):56–60. [PubMed] [Google Scholar]
  15. Kaplan H. S. On the natural history of the murine leukemias: presidential address. Cancer Res. 1967 Aug;27(8):1325–1340. [PubMed] [Google Scholar]
  16. LIEBERMAN M., HARAN-GHERA N., KAPLAN H. S. POTENTIATION OF VIRUS LEUKAEMOGENESIS IN C57BL MICE BY X-IRRADIATION OR URETHANE. Nature. 1964 Jul 25;203:420–422. doi: 10.1038/203420b0. [DOI] [PubMed] [Google Scholar]
  17. LIEBERMAN M., KAPLAN H. S. Leukemogenic activity of filtrates from radiation-induced lymphoid tumors of mice. Science. 1959 Aug 14;130(3372):387–388. doi: 10.1126/science.130.3372.387. [DOI] [PubMed] [Google Scholar]
  18. Lasfargues E. Y., Pillsbury N., Lasfargues J. C., Moore D. H. Release of leukemia C particles from murine cell lines infected with Bittner virus-containing inocula. Cancer Res. 1970 Jan;30(1):167–178. [PubMed] [Google Scholar]
  19. Lowy D. R., Rowe W. P., Teich N., Hartley J. W. Murine leukemia virus: high-frequency activation in vitro by 5-iododeoxyuridine and 5-bromodeoxyuridine. Science. 1971 Oct 8;174(4005):155–156. doi: 10.1126/science.174.4005.155. [DOI] [PubMed] [Google Scholar]
  20. MANAKER R. A., JENSEN E. M., KOROL W. LONG-TERM PROPAGATION OF A MURINE LEUKEMIA VIRUS IN AN ESTABLISHED CELL LINE. J Natl Cancer Inst. 1964 Aug;33:363–371. [PubMed] [Google Scholar]
  21. MOLONEY J. B. Biological studies on a lymphoid-leukemia virus extracted from sarcoma 37. I. Origin and introductory investigations. J Natl Cancer Inst. 1960 Apr;24:933–951. [PubMed] [Google Scholar]
  22. Nomura S., Bassin R. H., Fischinger P. J. Replication of radiation-induced murine leukemia virus in normal and transformed mouse cells. J Virol. 1972 Mar;9(3):494–502. doi: 10.1128/jvi.9.3.494-502.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. PERIES J., LEVY J. P., BOIRON M., BERNARD J. MULTIPLICATION OF RAUSCHER VIRUS IN CULTURES OF MOUSE KIDNEY CELLS. Nature. 1964 Aug 8;203:672–673. doi: 10.1038/203672a0. [DOI] [PubMed] [Google Scholar]
  24. RAUSCHER F. J. A virus-induced disease of mice characterized by erythrocytopoiesis and lymphoid leukemia. J Natl Cancer Inst. 1962 Sep;29:515–543. [PubMed] [Google Scholar]
  25. Ribacchi R., Giraldo G. Leukemia virus release in chemically or physically induced lymphomas in BALB-c mice. Natl Cancer Inst Monogr. 1966 Sep;22:701–711. [PubMed] [Google Scholar]
  26. Rowe W. P., Pugh W. E., Hartley J. W. Plaque assay techniques for murine leukemia viruses. Virology. 1970 Dec;42(4):1136–1139. doi: 10.1016/0042-6822(70)90362-4. [DOI] [PubMed] [Google Scholar]
  27. SINKOVICS J. G., HOWE C. D. GROWTH CHARACTERISTICS, VIRUS YIELD, AND INTERFERON ASSAY OF LEUKEMIC MOUSE SPLEEN TISSUE CULTURES. J Infect Dis. 1964 Oct;114:359–372. doi: 10.1093/infdis/114.4.359. [DOI] [PubMed] [Google Scholar]
  28. Sarma P. S., Cheong M. P., Hartley J. W., Huebner R. J. A viral interference test for mouse leukemia viruses. Virology. 1967 Sep;33(1):180–184. doi: 10.1016/0042-6822(67)90111-0. [DOI] [PubMed] [Google Scholar]
  29. TENNANT J. R. Derivation of a murine lymphoid leukemia virus. J Natl Cancer Inst. 1962 Jun;28:1291–1303. [PubMed] [Google Scholar]
  30. Tennant J. R. Characterization of two BALB-c infant thymus cell lines infected with lympholeukemogenic virus. J Natl Cancer Inst. 1969 May;42(5):739–748. [PubMed] [Google Scholar]
  31. Witte O. N., Weissman I. L., Kaplan H. S. Structural characteristics of some murine RNA tumor viruses studied by lactoperoxidase iodination. Proc Natl Acad Sci U S A. 1973 Jan;70(1):36–40. doi: 10.1073/pnas.70.1.36. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Woods W. A., Wivel N. A., Massicot J. G., Chirigos M. A. Characterization of a rapidly growing AKR lymphoblastic cell line maintaining Gross antigens and viral replication. Cancer Res. 1970 Aug;30(8):2147–2155. [PubMed] [Google Scholar]
  33. Wright B. S., Lasfargues J. C. Attenuation of the Rauscher murine leukemia virus through serial passages in tissue culture. Natl Cancer Inst Monogr. 1966 Sep;22:685–700. [PubMed] [Google Scholar]
  34. Wright B. S., Lasfargues J. C. Long-term propagation of the Rauscher murine leukemia virus in tissue culture. J Natl Cancer Inst. 1965 Aug;35(2):319–327. [PubMed] [Google Scholar]
  35. Yoshikura H., Hirokawa Y., Ikawa Y., Sugano H. Infectious but non-leukemogenic Friend leukemia virus obtained after prolonged cultivation in vitro. Int J Cancer. 1969 Sep 15;4(5):636–640. doi: 10.1002/ijc.2910040508. [DOI] [PubMed] [Google Scholar]

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