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. 1974 Dec;71(12):4980–4985. doi: 10.1073/pnas.71.12.4980

Induction of Endogenous Virus and of Thymidine Kinase by Bromodeoxyuridine in Cell Cultures Transformed by Friend Virus

W Ostertag *, G Roesler *, C J Krieg *, J Kind *, T Cole *, T Crozier *, G Gaedicke , G Steinheider *, N Kluge *, S Dube *
PMCID: PMC434023  PMID: 4531031

Abstract

Thymidine kinase positive (TK+) N type cell lines that had been transformed by spleen focus-forming virus were established by transformation with NB tropic Friend virus complex. Thymidine kinase deficient (TK-) cell clones were isolated. Some of these cell clones release 1000- to 100,000-fold reduced amounts of Friend virus complex as compared to the TK+ parental cell clone. TK- clones were grown in medium without BrdUrd. Some of these TK- clones can be induced to release endogenous helper virus and transforming spleen focus-forming virus on reexposure to 10-6-10-4 M BrdUrd. The induced Friend virus complex is of N host range as expected with induced endogenous virus in N-type cells. Before the induction of the endogenous virus spleen focus-forming virus complex, an induction of thymidine kinase (ATP:thymidine 5′-phosphotransferase, EC 2.7.1.75) activity is observed. The latter is possibly a prerequisite for the induction of endogenous virus in TK- cells. Induction of thymidine kinase activity and of endogenous virus is transient and always correlated. The role of BrdUrd and another thymidine analogue, azidothymidine, in interfering with C-type virus release in virus positive cells is discussed. Azidothymidine is unable to induce endogenous virus. Induction of endogenous virus by BrdUrd and inhibition of virus release in virus positive cells is apparently not caused by the same mechanism.

Keywords: erythroleukemia cells, differentiation, spleen focus-forming virus

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Selected References

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

  1. AXELRAD A. A., STEEVES R. A. ASSAY FOR FRIEND LEUKEMIA VIRUS: RAPID QUANTITATIVE METHOD BASED ON ENUMERATION OF MACROSCOPIC SPLEEN FOCI IN MICE. Virology. 1964 Nov;24:513–518. doi: 10.1016/0042-6822(64)90199-0. [DOI] [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. Clive D., Flamm W. G., Machesko M. R., Bernheim N. J. A mutational assay system using the thymidine kinase locus in mouse lymphoma cells. Mutat Res. 1972 Sep;16(7):77–87. doi: 10.1016/0027-5107(72)90066-8. [DOI] [PubMed] [Google Scholar]
  4. DUBBS D. R., KIT S. MUTANT STRAINS OF HERPES SIMPLEX DEFICIENT IN THYMIDINE KINASE-INDUCING ACTIVITY. Virology. 1964 Apr;22:493–502. doi: 10.1016/0042-6822(64)90070-4. [DOI] [PubMed] [Google Scholar]
  5. Fieldsteel A. H., Kurahara C. Moloney leukaemia virus as a helper in retrieving Friend virus from a non-infectious reticulum cell sarcoma. Nature. 1969 Sep 20;223(5212):1274–1274. doi: 10.1038/2231274a0. [DOI] [PubMed] [Google Scholar]
  6. Glaser R., Ogino T., Zimmerman J., Jr, Rapp F. Thymidine kinase activity in Burkitt lymphoblastoid somatic cell hybrids after induction of the EB virus. Proc Soc Exp Biol Med. 1973 Apr;142(4):1059–1062. doi: 10.3181/00379727-142-37176. [DOI] [PubMed] [Google Scholar]
  7. Hampar B., Derge J. G., Martos L. M., Walker J. L. Persistence of a repressed Epstein-Barr virus genome in Burkitt lymphoma cells made resistant to 5-bromodeoxyuridine. Proc Natl Acad Sci U S A. 1971 Dec;68(12):3185–3189. doi: 10.1073/pnas.68.12.3185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. KIT S., PIEKARSKI L. J., DUBBS D. R. Induction of thymidine kinase by vaccinia-infected mouse fibroblasts. J Mol Biol. 1963 Jan;6:22–33. doi: 10.1016/s0022-2836(63)80078-9. [DOI] [PubMed] [Google Scholar]
  9. Klement V., Nicolson M. O., Huebner R. J. Rescue of the genome of focus forming virus from rat non-productive lines by 5'-bromodeoxyruidine. Nat New Biol. 1971 Nov 3;234(44):12–14. doi: 10.1038/newbio234012a0. [DOI] [PubMed] [Google Scholar]
  10. Klemperer H. G., Haynes G. R., Shedden W. I., Watson D. H. A virus-specific thymidine kinase in BHK-21 cells infected with herpes simplex virus. Virology. 1967 Jan;31(1):120–128. doi: 10.1016/0042-6822(67)90015-3. [DOI] [PubMed] [Google Scholar]
  11. Kowollik G., Gaertner K., Langen P. Eine einfache Methode zur direkten Darstellung von O2,3'-Cyclo-2'-desoxy-nucleosiden. Tetrahedron Lett. 1969 Sep;(44):3863–3865. doi: 10.1016/s0040-4039(01)88532-4. [DOI] [PubMed] [Google Scholar]
  12. Lieber M. M., Livingston D. M., Todaro G. J. Superinduction of endogenous type C virus by 5-bromodeoxyuridine from transformed mouse clones. Science. 1973 Aug 3;181(4098):443–444. doi: 10.1126/science.181.4098.443. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Maisel J., Klement V., Lai M. M., Ostertag W., Duesberg P. Ribonucleic acid components of murine sarcoma and leukemia viruses. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3536–3540. doi: 10.1073/pnas.70.12.3536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ostertag W., Crozier T., Kluge N., Melderis H., Dube S. Action of 5-bromodeoxyuridine on the induction of haemoglobin synthesis in mouse leukaemia cells resistant to 5-BUdR. Nat New Biol. 1973 Jun 13;243(128):203–205. doi: 10.1038/newbio243203a0. [DOI] [PubMed] [Google Scholar]
  16. Ostertag W., Melderis H., Steinheider G., Kluge N., Dube S. Synthesis of mouse haemoglobin and globin mRNA in leukaemic cell cultures. Nat New Biol. 1972 Oct 25;239(95):231–234. doi: 10.1038/newbio239231a0. [DOI] [PubMed] [Google Scholar]
  17. PLUZNIK D. H., SACHS L. QUANTITATION OF A MURINE LEUKEMIA VIRUS WITH A SPLEEN COLONY ASSAY. J Natl Cancer Inst. 1964 Sep;33:535–546. [PubMed] [Google Scholar]
  18. ROWE W. P., BRODSKY I. A graded-response assay for the Friend leukemia virus. J Natl Cancer Inst. 1959 Dec;23:1239–1248. [PubMed] [Google Scholar]
  19. Roufa D. J., Sadow B. N., Caskey C. T. Derivation of TK- clones from revertant TK+ mammalian cells. Genetics. 1973 Nov;75(3):515–530. doi: 10.1093/genetics/75.3.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rowe W. P., Lowy D. R., Teich N., Hartley J. W. Some implications of the activation of murine leukemia virus by halogenated pyrimidines. Proc Natl Acad Sci U S A. 1972 Apr;69(4):1033–1035. doi: 10.1073/pnas.69.4.1033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Silagi S., Beju D., Wrathall J., Deharven E. Tumorigenicity, immunogenicity, and virus production in mouse melanoma cells treated with 5-bromodeoxyuridine. Proc Natl Acad Sci U S A. 1972 Nov;69(11):3443–3447. doi: 10.1073/pnas.69.11.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Steeves R. A., Eckner R. J., Mirand E. A., Priore R. L. Rapid assay of murine leukemia virus helper activity for Friend spleen focus-forming virus. J Natl Cancer Inst. 1971 Jun;46(6):1219–1228. [PubMed] [Google Scholar]
  24. Stephenson J. R., Reynolds R. K., Aaronson S. A. Isolation of temperature-sensitive mutants of murine leukemia virus. Virology. 1972 Jun;48(3):749–756. doi: 10.1016/0042-6822(72)90158-4. [DOI] [PubMed] [Google Scholar]
  25. Swetly P., Ostertag W. Friend virus release and induction of haemoglobin synthesis in erythroleukaemic cells respond differently to interferon. Nature. 1974 Oct 18;251(5476):642–644. doi: 10.1038/251642a0. [DOI] [PubMed] [Google Scholar]
  26. Teich N., Lowy D. R., Hartley J. W., Rowe W. P. Studies of the mechanism of induction of infectious murine leukemia virus from AKR mouse embryo cell lines by 5-iododeoxyuridine and 5-bromodeoxyuridine. Virology. 1973 Jan;51(1):163–173. doi: 10.1016/0042-6822(73)90376-0. [DOI] [PubMed] [Google Scholar]

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