Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1973 May 1;137(5):1163–1179. doi: 10.1084/jem.137.5.1163

TUMOR INDUCTION BY IMMUNOLOGICALLY ACTIVATED MURINE LEUKEMIA VIRUS

Martine Y K Armstrong 1, Nancy H Ruddle 1, Muriel B Lipman 1, Frank F Richards 1
PMCID: PMC2139244  PMID: 4144984

Abstract

A graft-vs.-host reaction (GVHR) was induced in young male CAFI and CB6F1 mice by the administration of BALB/cJ spleen cells. A proportion of such mice subsequently developed lymphoreticular rumors. Cell-free extracts (CFEs) prepared from the reticular tissues of CAF1 mice killed at intervals after the induction of the GVHR were tested for their capacity to produce the same tumors in a litter of syngeneic mice inoculated at birth. 12 of 29 (41.4%) such extracts were positive, causing lymphoreticular tumors in one or more littermate recipients. The positive CFEs came from donors killed at all stages of the GVHR, from tumor-bearing mice as well as from non-tumor-bearing mice. However, whereas less than 30% of CFEs from mice killed within 12 mo of GVHR induction were oncogenic, the incidence of oncogenic extracts from mice killed 12–15 mo after GVHR induction rose to 75%. None of the CFEs prepared from nine normal uninjected male CAF1 mice killed between the ages of 8 and 18 mo transmitted tumors to recipients. CFEs prepared from CAF1 mice with the GVHR were tested for infectious murine leukemia virus (MuLV) using the XC assay and also for complement-fixing (CF) group-specific MuLV antigen. Substantial titers of B-tropic MuLV and CF antigen were detected in at least half the extracts from mice killed 11–14 mo after GVHR induction. During the first few months of GVHR induction, MuLV titers were low and CF antigen was absent. Neither infectious MuLV nor CF antigen were detected in CFEs prepared from normal control mice. Serially passed CFEs originating from a CB6F1 GVHR-induced RCN caused similar tumors in successive generations of syngeneic recipient mice. These lymphoreticular tumors were shown to contain infectious MuLV, CF MuLV antigen, and C-type particles. These data together provide evidence that MuLV is activated during the GVHR and that it is responsible for the eventual development of lymphoreticular tumors.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

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

  1. AISENBERG A. C. Studies on delayed hypersensitivity in Hodgkin's disease. J Clin Invest. 1962 Nov;41:1964–1970. doi: 10.1172/JCI104654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aaronson S. A., Todaro G. J., Scolnick E. M. Induction of murine C-type viruses from clonal lines of virus-free BALB-3T3 cells. Science. 1971 Oct 8;174(4005):157–159. doi: 10.1126/science.174.4005.157. [DOI] [PubMed] [Google Scholar]
  3. Armstrong M. Y., Black F. L., Richards F. F. Tumour induction by cell-free extracts derived from mice with graft versus host disease. Nat New Biol. 1972 Feb 2;235(57):153–154. doi: 10.1038/newbio235153a0. [DOI] [PubMed] [Google Scholar]
  4. Armstrong M. Y., Gleichmann E., Gleichmann H., Beldotti L., Andre-Schwartz J., Schwartz R. S. Chronic allogeneic disease. II. Development of lymphomas. J Exp Med. 1970 Sep 1;132(3):417–439. doi: 10.1084/jem.132.3.417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bloom B. R., Jimenez L., Marcus P. I. A plaque assay for enumerating antigen-sensitive cells in delayed-type hypersensitivity. J Exp Med. 1970 Jul 1;132(1):16–30. doi: 10.1084/jem.132.1.16. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. CONE L., UHR J. W. IMMUNOLOGICAL DEFICIENCY DISORDERS ASSOCIATED WITH CHRONIC LYMPHOCYTIC LEUKEMIA AND MULTIPLE MYELOMA. J Clin Invest. 1964 Dec;43:2241–2248. doi: 10.1172/JCI105098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dalton A. J. Further analysis of the detailed structure of type B and C particles. J Natl Cancer Inst. 1972 Apr;48(4):1095–1099. [PubMed] [Google Scholar]
  8. Dalton A. J. RNA tumor viruses. Terminology and ultrastructural aspects of virion morphology and replication. J Natl Cancer Inst. 1972 Aug;49(2):323–327. [PubMed] [Google Scholar]
  9. Gerper P., Whang-Peng J., Monroe J. H. Transformation and chromosome changes induced by Epstein-Barr virus in normal human leukocyte cultures. Proc Natl Acad Sci U S A. 1969 Jul;63(3):740–747. doi: 10.1073/pnas.63.3.740. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gleichmann E., Gleichmann H., Schwartz R. S. Immunologic induction of malignant lymphoma: genetic factors in the graft-versus-host model. J Natl Cancer Inst. 1972 Sep;49(3):793–804. [PubMed] [Google Scholar]
  11. Hartley J. W., Rowe W. P., Capps W. I., Huebner R. J. Complement fixation and tissue culture assays for mouse leukemia viruses. Proc Natl Acad Sci U S A. 1965 May;53(5):931–938. doi: 10.1073/pnas.53.5.931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hartley J. W., Rowe W. P., Capps W. I., Huebner R. J. Isolation of naturally occurring viruses of the murine leukemia virus group in tissue culture. J Virol. 1969 Feb;3(2):126–132. doi: 10.1128/jvi.3.2.126-132.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hirsch M. S., Black P. H., Tracy G. S., Leibowitz S., Schwartz R. S. Leukemia virus activation in chronic allogeneic disease. Proc Natl Acad Sci U S A. 1970 Dec;67(4):1914–1917. doi: 10.1073/pnas.67.4.1914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hirsch M. S., Phillips S. M., Solnik C., Black P. H., Schwartz R. S., Carpenter C. B. Activation of leukemia viruses by graft-versus-host and mixed lymphocyte reactions in vitro. Proc Natl Acad Sci U S A. 1972 May;69(5):1069–1072. doi: 10.1073/pnas.69.5.1069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Huebner R. J., Todaro G. J. Oncogenes of RNA tumor viruses as determinants of cancer. Proc Natl Acad Sci U S A. 1969 Nov;64(3):1087–1094. doi: 10.1073/pnas.64.3.1087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kaplan H. S. On the natural history of the murine leukemias: presidential address. Cancer Res. 1967 Aug;27(8):1325–1340. [PubMed] [Google Scholar]
  17. Lewis R. M., Armstrong M. Y., André-Schwartz J., Muftuoglu A., Beldotti L., Schwartz R. S. Chronic allogeneic disease. I. Development of glomerulonephritis. J Exp Med. 1968 Oct 1;128(4):653–679. doi: 10.1084/jem.128.4.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. MOLLENHAUER H. H. PLASTIC EMBEDDING MIXTURES FOR USE IN ELECTRON MICROSCOPY. Stain Technol. 1964 Mar;39:111–114. [PubMed] [Google Scholar]
  20. 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]
  21. O'Connor G. T. Persistent immunologic stimulation as a factor in oncogenesis, with special reference to Burkitt's tumor. Am J Med. 1970 Mar;48(3):279–285. doi: 10.1016/0002-9343(70)90057-4. [DOI] [PubMed] [Google Scholar]
  22. Pincus T., Hartley J. W., Rowe W. P. A major genetic locus affecting resistance to infection with murine leukemia viruses. I. Tissue culture studies of naturally occurring viruses. J Exp Med. 1971 Jun 1;133(6):1219–1233. doi: 10.1084/jem.133.6.1219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Probert M., Epstein M. A. Morphological transformation in vitro of human fibroblasts by Epstein-Barr virus: preliminary observations. Science. 1972 Jan 14;175(4018):202–203. doi: 10.1126/science.175.4018.202. [DOI] [PubMed] [Google Scholar]
  24. REYNOLDS E. S. The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol. 1963 Apr;17:208–212. doi: 10.1083/jcb.17.1.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rowe W. P., Hartley J. W. Studies of genetic transmission of murine leukemia virus by AKR mice. II. Crosses with Fv-1 b strains of mice. J Exp Med. 1972 Nov 1;136(5):1286–1301. doi: 10.1084/jem.136.5.1286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rowe W. P., Pincus T. Quantitative studies of naturally occurring murine leukemia virus infection of AKR mice. J Exp Med. 1972 Feb 1;135(2):429–436. doi: 10.1084/jem.135.2.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Schwartz R. S., Beldotti L. Malignant lymphomas following allogenic disease: transition from an immunological to a neoplastic disorder. Science. 1965 Sep 24;149(3691):1511–1514. doi: 10.1126/science.149.3691.1511. [DOI] [PubMed] [Google Scholar]
  28. Schwartz R. S., Costea N. Autoimmune hemolytic anemia: clinical correlations and biological implications. Semin Hematol. 1966 Jan;3(1):2–26. [PubMed] [Google Scholar]
  29. Stephenson J. R., Aaronson S. A. Genetic factors influencing C-type RNA virus induction. J Exp Med. 1972 Jul 1;136(1):175–184. doi: 10.1084/jem.136.1.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Talal N., Sokoloff L., Barth W. F. Extrasalivary lymphoid abnormalities in Sjögren's syndrome (reticulum cell sarcoma, "pseudolymphoma," macroglobulinemia). Am J Med. 1967 Jul;43(1):50–65. doi: 10.1016/0002-9343(67)90148-9. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES