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. 1974 Jun;13(6):1291–1301. doi: 10.1128/jvi.13.6.1291-1301.1974

Studies of Nondefective Adenovirus 2-Simian Virus 40 Hybrid Viruses Transformation of Hamster Kidney Cells by Adenovirus 2 and the Nondefective Hybrid Viruses

Andrew M Lewis Jr 1,2, Alan S Rabson 1,2, Arthur S Levine 1,2
PMCID: PMC355448  PMID: 4364901

Abstract

Nonhybrid adenovirus 2 (Ad2) and five nondefective Ad2-simian virus 40 (SV40) hybrids (Ad2+ND1-Ad2+ND5) failed to produce tumors when injected into newborn hamsters. However, each of these agents transformed hamster kidney cells in vitro, and the transformed cell lines produced tumors when injected into suckling hamsters. Foci of cells transformed by the hybrids could not be distinguished from foci of cells transformed by nonhybrid Ad2. Histopathologically, tumors induced by the nondefective hybrid-transformed lines were of the adenovirus type with no areas of SV40-type fibrosarcoma. All of the cell lines studied contained Ad2 T antigen and Ad2 RNA. Only the B55HK1 line contained the three early SV40 antigens, U, TSTA, and T. The ND4HK1 line contained SV40 T and TSTA antigens (the latter antigen being detected only after 48 to 49 tissue culture passages) and SV40 RNA. The ND2HK2 line contained SV40 RNA but no detectable SV40 antigens; the other hybrid-transformed lines contained no SV40 RNA. The transformation of hamster cells by the nondefective Ad2-SV40 hybrids seemed to be caused by the Ad2 genome and could not be attributed to the regions of the SV40 genome contained within the hybrids. Additionally, these results indicate that interactions between the genomes of the nondefective hybrid viruses and the hamster cells they transform are complex and could involve the site of integration, the size of the incorporated viral genome, the transcription or translation of the viral genome, or various combinations of these processes.

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  1. ASHKENAZI A., MELNICK J. L. Tumorigencity of simian papovavirus SV40 and of virus-transformed cells. J Natl Cancer Inst. 1963 Jun;30:1227–1265. [PubMed] [Google Scholar]
  2. BLACK P. H., CRAWFORD E. M., CRAWFORD L. V. THE PURIFICATION OF SIMIAN VIRUS 40. Virology. 1964 Nov;24:381–387. doi: 10.1016/0042-6822(64)90175-8. [DOI] [PubMed] [Google Scholar]
  3. BLACK P. H., ROWE W. P., COOPER H. L. AN ANALYSIS OF SV 40-INDUCED TRANSFORMATION OF HAMSTER KIDNEY TISSUE IN VITRO. II. STUDIES OF THREE CLONES DERIVED FROM A CONTINUOUS LINE OF TRANSFORMED CELLS. Proc Natl Acad Sci U S A. 1963 Nov;50:847–854. doi: 10.1073/pnas.50.5.847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BLACK P. H., ROWE W. P., TURNER H. C., HUEBNER R. J. A SPECIFIC COMPLEMENT-FIXING ANTIGEN PRESENT IN SV40 TUMOR AND TRANSFORMED CELLS. Proc Natl Acad Sci U S A. 1963 Dec;50:1148–1156. doi: 10.1073/pnas.50.6.1148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berman L. D., Black P. H. Morphologic reflections of viral genome activity in viral oncogenesis of hamsters. Prog Exp Tumor Res. 1972;16:497–516. doi: 10.1159/000393386. [DOI] [PubMed] [Google Scholar]
  6. Collins M. J., Jr, Parker J. C. Murine virus contaminants of leukemia viruses and transplantable tumors. J Natl Cancer Inst. 1972 Oct;49(4):1139–1143. [PubMed] [Google Scholar]
  7. Crumpacker C. S., Henry P. H., Kakefuda T., Rowe W. P., Levin M. J., Lewis A. M., Jr Studies of nondefective adenovirus 2-simian virus 40 hybrid viruses. 3. Base composition, molecular weight, and conformation of the Ad2+ND genome. J Virol. 1971 Mar;7(3):352–358. doi: 10.1128/jvi.7.3.352-358.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Diamandopoulos G. T., Enders J. F. Comparison of the cytomorphologic characteristics of in vitro SV40-transformed hamster embryo cells with the histologic features of the neoplasms which they induce in the homologous host. Am J Pathol. 1966 Sep;49(3):397–417. [PMC free article] [PubMed] [Google Scholar]
  9. EDDY B. E., BORMAN G. S., BERKELEY W. H., YOUNG R. D. Tumors induced in hamsters by injection of rhesus monkey kidney cell extracts. Proc Soc Exp Biol Med. 1961 May;107:191–197. doi: 10.3181/00379727-107-26576. [DOI] [PubMed] [Google Scholar]
  10. Freeman A. E., Black P. H., Vanderpool E. A., Henry P. H., Austin J. B., Huebner R. J. Transformation of primary rat embryo cells by adenovirus type 2. Proc Natl Acad Sci U S A. 1967 Sep;58(3):1205–1212. doi: 10.1073/pnas.58.3.1205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Freeman A. E., Calisher C. H., Price P. J., Turner H. C., Huebner R. J. Calcium sensitivity of cell cultures derived from adenovirus-induced tumors. Proc Soc Exp Biol Med. 1966 Jul;122(3):835–840. doi: 10.3181/00379727-122-31264. [DOI] [PubMed] [Google Scholar]
  12. GIRARDI A. J., SWEET B. H., SLOTNICK V. B., HILLEMAN M. R. Development of tumors in hamsters inoculated in the neonatal period with vacuolating virus, SV-40. Proc Soc Exp Biol Med. 1962 Mar;109:649–660. doi: 10.3181/00379727-109-27298. [DOI] [PubMed] [Google Scholar]
  13. GOLDNER H., GIRARDI A. J., LARSON V. M., HILLEMAN M. R. INTERRUPTION OF SV-40 VIRUS TUMORIGENESIS USING IRRADIATED HOMOLOGOUS TUMOR ANTIGEN. Proc Soc Exp Biol Med. 1964 Dec;117:851–857. doi: 10.3181/00379727-117-29717. [DOI] [PubMed] [Google Scholar]
  14. GREEN M., PINA M. BIOCHEMICAL STUDIES ON ADENOVIRUS MULTIPLICATION, VI. PROPERTIES OF HIGHLY PURIFIED TUMORIGENIC HUMAN ADENOVIRUSES AND THEIR DNA. Proc Natl Acad Sci U S A. 1964 Jun;51:1251–1259. doi: 10.1073/pnas.51.6.1251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Garon C. F., Berry K. W., Hierholzer J. C., Rose J. A. Mapping of base sequence heterologies between genomes from different adenovirus serotypes. Virology. 1973 Aug;54(2):414–426. doi: 10.1016/0042-6822(73)90153-0. [DOI] [PubMed] [Google Scholar]
  16. Gerber P. Studies on the transfer of subviral infectivity from SV40-induced hamster tumor cells to indicator cells. Virology. 1966 Apr;28(4):501–509. doi: 10.1016/0042-6822(66)90234-0. [DOI] [PubMed] [Google Scholar]
  17. HUEBNER R. J., CHANOCK R. M., RUBIN B. A., CASEY M. J. INDUCTION BY ADENOVIRUS TYPE 7 OF TUMORS IN HAMSTERS HAVING THE ANTIGENIC CHARACTERISTICS OF SV40 VIRUS. Proc Natl Acad Sci U S A. 1964 Dec;52:1333–1340. doi: 10.1073/pnas.52.6.1333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. HUEBNER R. J., ROWE W. P., TURNER H. C., LANE W. T. SPECIFIC ADENOVIRUS COMPLEMENT-FIXING ANTIGENS IN VIRUS-FREE HAMSTER AND RAT TUMORS. Proc Natl Acad Sci U S A. 1963 Aug;50:379–389. doi: 10.1073/pnas.50.2.379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hayflick L. Tissue cultures and mycoplasmas. Tex Rep Biol Med. 1965 Jun;23(Suppl):285+–285+. [PubMed] [Google Scholar]
  20. Henry P. H., Schnipper L. E., Samaha R. J., Crumpacker C. S., Lewis A. M., Jr, Levine A. S. Studies of nondefective adenovirus 2-simian virus 40 hybrid viruses. VI. Characterization of the DNA from five nondefective hybrid viruses. J Virol. 1973 May;11(5):665–671. doi: 10.1128/jvi.11.5.665-671.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Igel H. J., Black P. H. In vitro transformation by the adenovirus-SV40 hybrid viruses. 3. Morphology of tumors induced with transformed cells. J Exp Med. 1967 Apr 1;125(4):647–656. doi: 10.1084/jem.125.4.647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. KHERA K. S., ASHKENAZI A., RAPP F., MELNICK J. L. IMMUNITY IN HAMSTERS TO CELLS TRANSFORMED IN VITRO AND IN VIVO BY SV40. TESTS FOR ANTIGENIC RELATIONSHIP AMONG THE PAPOVAVIRUSES. J Immunol. 1963 Nov;91:604–613. [PubMed] [Google Scholar]
  23. Kelly T. J., Jr, Lewis A. M., Jr Use of nondefective adenovirus-simian virus 40 hybrids for mapping the simian virus 40 genome. J Virol. 1973 Sep;12(3):643–652. doi: 10.1128/jvi.12.3.643-652.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kirschstein R. L., Rabson A. S., Paul F. J., Peters E. A. Double infection of newborn Syrian hamsters with simian virus 40 and human adenovirus 12. Cancer Res. 1966 Jul;26(7):1361–1364. [PubMed] [Google Scholar]
  25. Levin M. J., Crumpacker C. S., Lewis A. M., Jr, Oxman M. N., Henry P. H., Rowe W. P. Studies of nondefective adenovirus 2-simian virus 40 hybrid viruses. II. Relationship of adenovirus 2 deoxyribonucleic acid and simian virus 40 deoxyribonucleic acid in the Ad2+ND genome. J Virol. 1971 Mar;7(3):343–351. doi: 10.1128/jvi.7.3.343-351.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Levin M. J., Oxman M. N., Diamandopoulos G. T., Levine A. S., Henry P. H., Enders J. F. Virus-specific nucleic acids in SV40-exposed hamster embryo cell lines: correlation with S and T antigens. Proc Natl Acad Sci U S A. 1969 Feb;62(2):589–596. doi: 10.1073/pnas.62.2.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Levine A. S., Levin M. J., Oxman M. N., Lewis A. M., Jr Studies of nondefective adenovirus 2-simian virus 40 hybrid viruses. VII. Characterization of the simian virus 40 RNA species induced by five nondefective hybrid viruses. J Virol. 1973 May;11(5):672–681. doi: 10.1128/jvi.11.5.672-681.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lewis A. M., Jr, Levin M. J., Wiese W. H., Crumpacker C. S., Henry P. H. A nondefective (competent) adenovirus-SV40 hybrid isolated from the AD.2-SV40 hybrid population. Proc Natl Acad Sci U S A. 1969 Aug;63(4):1128–1135. doi: 10.1073/pnas.63.4.1128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Lewis A. M., Jr, Levine A. S., Crumpacker C. S., Levin M. J., Samaha R. J., Henry P. H. Studies of nondefective adenovirus 2-simian virus 40 hybrid viruses. V. Isolation of additional hybrids which differ in their simian virus 40-specific biological properties. J Virol. 1973 May;11(5):655–664. doi: 10.1128/jvi.11.5.655-664.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lewis A. M., Jr, Rowe W. P. Studies of nondefective Adenovirus 2-Simian virus 40 hybrid viruses. 8. Association of Simian virus 40 transplantation antigen with a specific region of the early viral genome. J Virol. 1973 Oct;12(4):836–840. doi: 10.1128/jvi.12.4.836-840.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Lewis A. M., Jr, Rowe W. P. Studies on nondefective adenovirus-simian virus 40 hybrid viruses. I. A newly characterized simian virus 40 antigen induced by the Ad2+ND 1 virus. J Virol. 1971 Feb;7(2):189–197. doi: 10.1128/jvi.7.2.189-197.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Lewis A. M., Wiese W. H., Rowe W. P. The presence of antibodies in human serum to early (T) adenovirus antigens. Proc Natl Acad Sci U S A. 1967 Mar;57(3):622–629. doi: 10.1073/pnas.57.3.622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. MACPHERSON I., MONTAGNIER L. AGAR SUSPENSION CULTURE FOR THE SELECTIVE ASSAY OF CELLS TRANSFORMED BY POLYOMA VIRUS. Virology. 1964 Jun;23:291–294. doi: 10.1016/0042-6822(64)90301-0. [DOI] [PubMed] [Google Scholar]
  34. McAllister R. M., Nicolson M. O., Lewis A. M., Jr, Macpherson I., Huebner R. J. Transformation of rat embryo cells by adenovirus type 1. J Gen Virol. 1969 Jan;4(1):29–36. doi: 10.1099/0022-1317-4-1-29. [DOI] [PubMed] [Google Scholar]
  35. McAllister R. M., Nicolson M. O., Reed G., Kern J., Gilden R. V., Huebner R. J. Transformation of rodent cells by adenovirus 19 and other group D adenoviruses. J Natl Cancer Inst. 1969 Oct;43(4):917–923. [PubMed] [Google Scholar]
  36. Merril C. R., Geier M. R., Petricciani J. C. Bacterial virus gene expression in human cells. Nature. 1971 Oct 8;233(5319):398–400. doi: 10.1038/233398a0. [DOI] [PubMed] [Google Scholar]
  37. Morrow J. F., Berg P., Kelly T. J., Jr, Lewis A. M., Jr Mapping of simian virus 40 early functions on the viral chromosome. J Virol. 1973 Sep;12(3):653–658. doi: 10.1128/jvi.12.3.653-658.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. POPE J. H., ROWE W. P. DETECTION OF SPECIFIC ANTIGEN IN SV40-TRANSFORMED CELLS BY IMMUNOFLUORESCENCE. J Exp Med. 1964 Aug 1;120:121–128. doi: 10.1084/jem.120.2.121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. POPE J. H., ROWE W. P. IMMUNOFLUORESCENT STUDIES OF ADENOVIRUS 12 TUMORS AND OF CELLS TRANSFORMED OR INFECTED BY ADENOVIRUSES. J Exp Med. 1964 Oct 1;120:577–588. doi: 10.1084/jem.120.4.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. RABSON A. S., KIRSCHSTEIN R. L. Induction of malignancy in vitro in newborn hamster kidney tissue infected with simian vacuolating virus (SV40). Proc Soc Exp Biol Med. 1962 Nov;111:323–328. doi: 10.3181/00379727-111-27780. [DOI] [PubMed] [Google Scholar]
  41. SHEIN H. M., ENDERS J. F., LEVINTHAL J. D., BURKET A. E. Transformation induced by simian virus 40 in newborn Syrian hamster renal cell cultures. Proc Natl Acad Sci U S A. 1963 Jan 15;49:28–34. doi: 10.1073/pnas.49.1.28. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Schnipper L. E., Lewis A. M., Jr, Levine A. S. Induction of cellular DNA synthesis by the nondefective Adenovirus 2-Simian virus 40 hybrid viruses. J Virol. 1973 Oct;12(4):940–943. doi: 10.1128/jvi.12.4.940-943.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Smith R. W., Morganroth J., Mora P. T. SV40 virus-induced tumour specific transplantation antigen in cultured mouse cells. Nature. 1970 Jul 11;227(5254):141–145. doi: 10.1038/227141a0. [DOI] [PubMed] [Google Scholar]
  44. Williams J. F. Oncogenic transformation of hamster embryo cells in vitro by adenovirus type 5. Nature. 1973 May 18;243(5403):162–163. doi: 10.1038/243162a0. [DOI] [PubMed] [Google Scholar]

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