Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1974 May;71(5):1705–1709. doi: 10.1073/pnas.71.5.1705

The Presence of Unique DNA Sequences after Viral Induction of Leukemia in Mice

R W Sweet 1,2, N C Goodman 1,2, J-R Cho 1,2, R M Ruprecht 1,2, R R Redfield 1,2, S Spiegelman 1,2
PMCID: PMC388307  PMID: 4525459

Abstract

From previous studies, lymphocyte DNA from human leukemias and DNA from involved tissues of patients with Hodgkin's disease or Burkitt's lymphoma contain sequences that are absent from their normal counterparts. These sequences are related to those found in particulate elements associated with these neoplasias and possessing biochemical properties characteristic of RNA tumor viruses. Similar observations have been made of unique sequences related to those of the feline virus RD-114 and found in spontaneous mastocytomas in cats. Here we extend these results to the classical murine model of virus-induced leukemias.

Splenic DNA from BALB/c mice with leukemia induced by Rauscher leukemia virus (RLV) possess some RLV-related sequences that do not exist in normal BALB/c DNA. Furthermore, these leukemia-specific sequences were absent in all other mouse strains examined, including AKR, a strain with a high incidence of spontaneous leukemia.

The DNA of all noninfected mouse strains possesses considerable homology with the RLV genome. Temperature denaturation studies indicate, however, that although the RLV-related sequences found in all normal mice are similar to each other, they are not exactly homologous with RLV sequences.

We conclude that RLV-induced leukemia in BALB/c results in the insertion of RLV sequences into cellular DNA that itself possesses only partial homology with the RLV genome.

Keywords: RNA tumor virus, nucleic acid hybridization, insertion of viral DNA

Full text

PDF
1709

Selected References

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

  1. Baluda M. A. Widespread presence, in chickens, of DNA complementary to the RNA genome of avian leukosis viruses. Proc Natl Acad Sci U S A. 1972 Mar;69(3):576–580. doi: 10.1073/pnas.69.3.576. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baxt W. G., Spiegelman S. Nuclear DNA sequences present in human leukemic cells and absent in normal leukocytes. Proc Natl Acad Sci U S A. 1972 Dec;69(12):3737–3741. doi: 10.1073/pnas.69.12.3737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baxt W., Hehlmann R., Spiegelman S. Human leukaemic cells contain reverse transcriptase associated with a high molecular weight virus-related RNA. Nat New Biol. 1972 Nov 15;240(98):72–75. doi: 10.1038/newbio240072a0. [DOI] [PubMed] [Google Scholar]
  4. Baxt W., Yates J. W., Wallace H. J., Jr, Holland J. F., Spiegelman S. Leukemia-specific DNA sequences in leukocytes of the leukemic member of identical twins. Proc Natl Acad Sci U S A. 1973 Sep;70(9):2629–2632. doi: 10.1073/pnas.70.9.2629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. FINK M. A., RAUSCHER F. J. IMMUNE REACTIONS TO A MURINE LEUKEMIA VIRUS. I. INDUCTION OF IMMUNITY TO INFECTION WITH VIRUS IN THE NATURAL HOST. J Natl Cancer Inst. 1964 May;32:1075–1082. [PubMed] [Google Scholar]
  6. Gelb L. D., Milstien J. B., Martin M. A., Aaronson S. A. Characterization of murine leukaemia virus-specific DNA present in normal mouse cells. Nat New Biol. 1973 Jul 18;244(133):76–79. doi: 10.1038/newbio244076a0. [DOI] [PubMed] [Google Scholar]
  7. Goldfeder A. Urethan and x-ray effects on mice of a tumor-resistant strain, X-Gf. Cancer Res. 1972 Dec;32(12):2771–2777. [PubMed] [Google Scholar]
  8. Goodman N. C., Ruprecht R. M., Sweet R. W., Massey R., Deinhardt F., Spiegelman S. Viral-related DNA sequences before and after transformation by RNA tumor viruses. Int J Cancer. 1973 Nov 15;12(3):752–760. doi: 10.1002/ijc.2910120323. [DOI] [PubMed] [Google Scholar]
  9. Hehlmann R., Baxt W., Kufe D., Spiegelman S. Molecular evidence for a viral etiology of human leukemias, lymphomas, and sarcomas. Am J Clin Pathol. 1973 Jul;60(1):65–79. doi: 10.1093/ajcp/60.1.65. [DOI] [PubMed] [Google Scholar]
  10. Hehlmann R., Kufe D., Spiegelman S. RNA in human leukemic cells related to the RNA of a mouse leukemia virus (leukocytes-RNA-DNA hybridization-rauscher virus-polysomal RNA). Proc Natl Acad Sci U S A. 1972 Feb;69(2):435–439. doi: 10.1073/pnas.69.2.435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Kufe D. W., Peters W. P., Spiegelman S. Unique nuclear DNA sequences in the involved tissues of Hodgkin's and Burkitt's lymphomas. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3810–3814. doi: 10.1073/pnas.70.12.3810. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Laird C. D., McConaughy B. L., McCarthy B. J. Rate of fixation of nucleotide substitutions in evolution. Nature. 1969 Oct 11;224(5215):149–154. doi: 10.1038/224149a0. [DOI] [PubMed] [Google Scholar]
  14. Neiman P. E. Measurement of endogenous leukosis virus nucleotide sequences in the DNA of normal avian embryos by RNA-DNA hybridization. Virology. 1973 May;53(1):196–203. doi: 10.1016/0042-6822(73)90478-9. [DOI] [PubMed] [Google Scholar]
  15. Neiman P. E. Rous sarcoma virus nucleotide sequences in cellular DNA: measurement by RNA-DNA hybridization. Science. 1972 Nov 17;178(4062):750–753. doi: 10.1126/science.178.4062.750. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Ruprecht R. M., Goodman N. C., Spiegelman S. Conditions for the selective synthesis of DNA complementary to template RNA. Biochim Biophys Acta. 1973 Jan 19;294(2):192–203. [PubMed] [Google Scholar]
  18. Ruprecht R. M., Goodman N. C., Spiegelman S. Determination of natural host taxonomy of RNA tumor viruses by molecular hybridization: application to RD-114, a candidate human virus. Proc Natl Acad Sci U S A. 1973 May;70(5):1437–1441. doi: 10.1073/pnas.70.5.1437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Spiegelman S., Burny A., Das M. R., Keydar J., Schlom J., Travnicek M., Watson K. Characterization of the products of DNA-directed DNA polymerases in oncogenic RNA viruses. Nature. 1970 Aug 8;227(5258):563–567. doi: 10.1038/227563a0. [DOI] [PubMed] [Google Scholar]
  20. Todaro G. J., Huebner R. J. N.A.S. symposium: new evidence as the basis for increased efforts in cancer research. Proc Natl Acad Sci U S A. 1972 Apr;69(4):1009–1015. doi: 10.1073/pnas.69.4.1009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Varmus H. E., Bishop J. M., Nowinski R. C., Sarker N. H. Mammary tumour virus specific nucleotide sequences in mouse DNA. Nat New Biol. 1972 Aug 9;238(84):189–191. doi: 10.1038/newbio238189a0. [DOI] [PubMed] [Google Scholar]
  22. Varmus H. E., Bishop J. M., Vogt P. K. Appearance of virus-specific DNA in mammalian cells following transformation by Rous sarcoma virus. J Mol Biol. 1973 Mar 15;74(4):613–626. doi: 10.1016/0022-2836(73)90052-1. [DOI] [PubMed] [Google Scholar]
  23. Varmus H. E., Vogt P. K., Bishop J. M. Integration of deoxyribonucleic acid specific for Rous sarcoma virus after infection of permissive and nonpermissive hosts. Proc Natl Acad Sci U S A. 1973 Nov;70(11):3067–3071. doi: 10.1073/pnas.70.11.3067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Viola M. V., White L. R. Differences in murine leukaemia virus-specific DNA sequences in normal and malignant cells. Nature. 1973 Dec 21;246(5434):485–487. doi: 10.1038/246485a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES