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. 1965 Jun 1;121(6):935–944. doi: 10.1084/jem.121.6.935

DIFFERENTIAL EFFECTS OF INHIBITORS ON THE STEPS LEADING TO THE FORMATION OF SV40 TUMOR AND VIRUS ANTIGENS

F Rapp 1, J S Butel 1, L A Feldman 1, T Kitahara 1, J L Melnick 1
PMCID: PMC2138018  PMID: 14319408

Abstract

The effect of DNA antagonists and various antibiotics on steps in the synthesis of SV40 virus in green monkey kidney cells was investigated. Both the early forming tumor (T) antigen, as well as the later synthesized virus (V) antigen, were synthesized in the presence of fluorouracil and iododeoxyuridine. Cytosine arabinoside (and fluorodeoxyuridine in starved cells) prevented synthesis of V antigen but not T antigen. The synthesis of T antigen therefore does not require synthesis of virus DNA. Virus particles formed only in the presence of the iododeoxyuridine and they were non-infectious. Actinomycin D inhibited synthesis of both tumor and virus antigens, suggesting that the synthesis of these antigens involves DNA-dependent RNA. Puromycin allowed synthesis of the T antigen which remained localized at the nucleolar membrane. This finding with puromycin suggests that the T antigen is a protein of low molecular weight. Virus antigen forming in the presence of mitomycin C, p-fluorophenylalanine, iododeoxyuridine, or fluorouracil was distributed atypically. These inhibitors caused the V antigen to be diffusely spread throughout the nucleus, or to be concentrated at the nuclear membrane.

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Selected References

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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., 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]
  3. CARDEILHAC P. T., COHEN S. S. SOME METABOLIC PROPERTIES OF NUCLEOTIDES OF 1-BETA-D-ARABINO-FURANOSYLCYTOSINE. Cancer Res. 1964 Oct;24:1595–1603. [PubMed] [Google Scholar]
  4. CHU M. Y., FISCHER G. A. A proposed mechanism of action of 1-beta-D-arabinofuranosyl-cytosine as an inhibitor of the growth of leukemic cells. Biochem Pharmacol. 1962 Jun;11:423–430. doi: 10.1016/0006-2952(62)90225-3. [DOI] [PubMed] [Google Scholar]
  5. DARKEN M. A. PUROMYCIN INHIBITION OF PROTEIN SYNTHESIS. Pharmacol Rev. 1964 Sep;16:223–243. [PubMed] [Google Scholar]
  6. GOLDBERG I. H., REICH E. ACTINOMYCIN INHIBITION OF RNA SYNTHESIS DIRECTED BY DNA. Fed Proc. 1964 Sep-Oct;23:958–964. [PubMed] [Google Scholar]
  7. 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]
  8. MAYOR H. D., STINEBAUGH S. E., JAMISON R. M., JORDAN L. E., MELNICK J. L. Immunofluorescent, cytochemical, and microcytological studies on the growth of the simian vacuolating virus (SV-40) in tissue culture. Exp Mol Pathol. 1962 Oct;1:397–416. doi: 10.1016/0014-4800(62)90033-3. [DOI] [PubMed] [Google Scholar]
  9. MELNICK J. L., STINEBAUGH S. E., RAPP F. INCOMPLETE SIMIAN PAPOVAVIRUS SV40. FORMATION OF NON-INFECTIOUS VIRAL ANTIGEN IN THE PRESENCE OF FLUOROURACIL. J Exp Med. 1964 Feb 1;119:313–326. doi: 10.1084/jem.119.2.313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. NATHANS D. INHIBITION OF PROTEIN SYNTHESIS BY PUROMYCIN. Fed Proc. 1964 Sep-Oct;23:984–989. [PubMed] [Google Scholar]
  11. PRUSOFF W. H., BAKHLE Y. S., MCCREA J. F. INCORPORATION OF 5-IODO-2'-DEOXYURIDINE INTO THE DEOXYRIBONUCLEIC ACID OF VACCINIA VIRUS. Nature. 1963 Sep 28;199:1310–1311. doi: 10.1038/1991310a0. [DOI] [PubMed] [Google Scholar]
  12. RAPP F. INHIBITION BY METABOLIC ANALOGUES OF PLAQUE FORMATION BY HERPES ZOSTER AND HERPES SIMPLEX VIRUSES. J Immunol. 1964 Oct;93:643–648. [PubMed] [Google Scholar]
  13. RAPP F., KITAHARA T., BUTEL J. S., MELNICK J. L. SYNTHESIS OF SV40 TUMOR ANTIGEN DURING REPLICATION OF SIMIAN PAPOVAVIRUS (SV40). Proc Natl Acad Sci U S A. 1964 Nov;52:1138–1142. doi: 10.1073/pnas.52.5.1138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. RAPP F. Localization of antinuclear factors from lupus erythematosus sera in tissue culture. J Immunol. 1962 Jun;88:732–740. [PubMed] [Google Scholar]
  15. RAPP F., MELNICK J. L., BUTEL J. S., KITAHARA T. THE INCORPORATION OF SV40 MATERIAL INTO ADENOVIRUS 7 AS MEASURED BY INTRANUCLEAR SYNTHESIS OF SV40 TUMOR ANTIGEN. Proc Natl Acad Sci U S A. 1964 Dec;52:1348–1352. doi: 10.1073/pnas.52.6.1348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. RAPP F., MELNICK J. L., KITAHARA T. TUMOR AND VIRUS ANTIGENS OF SIMIAN VIRUS 40: DIFFERENTIAL INHIBITION OF SYNTHESIS BY CYTOSINE ARABINOSIDE. Science. 1965 Feb 5;147(3658):625–627. doi: 10.1126/science.147.3658.625. [DOI] [PubMed] [Google Scholar]
  17. RAPP F., VANDERSLICE D. SPREAD OF ZOSTER VIRUS IN HUMAN EMBRYONIC LUNG CELLS AND THE INHIBITORY EFFECT OF LODODEOXYURIDINE. Virology. 1964 Mar;22:321–330. doi: 10.1016/0042-6822(64)90023-6. [DOI] [PubMed] [Google Scholar]
  18. RODRIGUEZ J., DEINHARDT F. Preparation of a semipermanent mounting medium for fluorescent antibody studies. Virology. 1960 Oct;12:316–317. doi: 10.1016/0042-6822(60)90205-1. [DOI] [PubMed] [Google Scholar]
  19. ROWE W. P., BAUM S. G. EVIDENCE FOR A POSSIBLE GENETIC HYBRID BETWEEN ADENOVIRUS TYPE 7 AND SV40 VIRUSES. Proc Natl Acad Sci U S A. 1964 Dec;52:1340–1347. doi: 10.1073/pnas.52.6.1340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. SABIN A. B., KOCH M. A. SOURCE OF GENETIC INFORMATION FOR SPECIFIC COMPLEMENT-FIXING ANTIGENS IN SV40 VIRUS-INDUCED TUMORS. Proc Natl Acad Sci U S A. 1964 Nov;52:1131–1138. doi: 10.1073/pnas.52.5.1131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. SMITH K. O., DUKES C. D. EFFECTS OF 5-IDOO-2-DESOXYURIDINE (IDU) ON HERPESVIRUS SYNTHESIS AND SURVIVAL IN INFECTED CELLS. J Immunol. 1964 Apr;92:550–554. [PubMed] [Google Scholar]
  22. SMITH K. O., MELNICK J. L. A method for staining virus particles and identifying their nucleic acid type in the electron microscope. Virology. 1962 Jul;17:480–490. doi: 10.1016/0042-6822(62)90143-5. [DOI] [PubMed] [Google Scholar]

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