Skip to main content
NCBI 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 Apr;71(4):1250–1254. doi: 10.1073/pnas.71.4.1250

Simian Virus 40 DNA Sequences in DNA of Healthy Adult Mice Derived from Preimplantation Blastocysts Injected with Viral DNA

Rudolf Jaenisch *, Beatrice Mintz †,†
PMCID: PMC388203  PMID: 4364530

Abstract

Explanted mouse blastocysts were microinjected in the blastocoel cavity with simian virus 40 (SV40) viral DNA. After surgical transfer to the uteri of pseudopregnant surrogate mothers, approximately 40% of the blastocysts developed to term and became healthy adults without apparent tumors at 1 year of age. Molecular hybridization tests for the presence of SV40-specific DNA sequences were conducted on DNA extracted from various organs of these animals. Between 0.5 and 13 SV40 genome equivalents per diploid mouse DNA value were found in some organs of approximately 40% of the adult survivors; this represents a substantial augmentation of the amount administered per embryo. The results are consistent with the working hypothesis that the SV40 DNA may have been integrated into the host genome; alternatively, the viral DNA may have replicated as an extrachromosomal entity or by lytic infection in a few permissive cells. Persistence of the viral DNA from preimplantation stages to adult life may thus provide a new tool for experimental investigation of vertical transmission and expression of tumor viruses.

Keywords: blastocyst microinjection in vitro, development, DNA reassociation kinetics of simian virus 40

Full text

PDF
1250

Selected References

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

  1. 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]
  2. Aoki T., Todaro G. J. Antigenic properties of endogenous type-C viruses from spontaneously transformed clones of BALB-3T3. Proc Natl Acad Sci U S A. 1973 May;70(5):1598–1602. doi: 10.1073/pnas.70.5.1598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bentvelzen P., Daams J. H., Hageman P., Calafat J. Genetic transmission of viruses that incite mammary tumor in mice. Proc Natl Acad Sci U S A. 1970 Sep;67(1):377–384. doi: 10.1073/pnas.67.1.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brinster R. L. Studies on the development of mouse embryos in vitro. IV. Interaction of energy sources. J Reprod Fertil. 1965 Oct;10(2):227–240. doi: 10.1530/jrf.0.0100227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Britten R. J., Kohne D. E. Repeated sequences in DNA. Hundreds of thousands of copies of DNA sequences have been incorporated into the genomes of higher organisms. Science. 1968 Aug 9;161(3841):529–540. doi: 10.1126/science.161.3841.529. [DOI] [PubMed] [Google Scholar]
  6. Frenkel N., Roizman B., Cassai E., Nahmias A. A DNA fragment of Herpes simplex 2 and its transcription in human cervical cancer tissue. Proc Natl Acad Sci U S A. 1972 Dec;69(12):3784–3789. doi: 10.1073/pnas.69.12.3784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gelb L. D., Kohne D. E., Martin M. A. Quantitation of Simian virus 40 sequences in African green monkey, mouse and virus-transformed cell genomes. J Mol Biol. 1971 Apr 14;57(1):129–145. doi: 10.1016/0022-2836(71)90123-9. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Jaenisch R., Levine A. DNA replication in SV40-infected cells. V. Circular and catenated oligomers of SV40 DNA. Virology. 1971 Jun;44(3):480–493. doi: 10.1016/0042-6822(71)90361-8. [DOI] [PubMed] [Google Scholar]
  10. Jovin T. M., Englund P. T., Bertsch L. L. Enzymatic synthesis of deoxyribonucleic acid. XXVI. Physical and chemical studies of a homogeneous deoxyribonucleic acid polymerase. J Biol Chem. 1969 Jun 10;244(11):2996–3008. [PubMed] [Google Scholar]
  11. Payne L. N., Chubb R. C. Studies on the nature and genetic control of an antigen in normal chick embryos which reacts in the COFAL test. J Gen Virol. 1968 Dec;3(3):379–391. doi: 10.1099/0022-1317-3-3-379. [DOI] [PubMed] [Google Scholar]
  12. Pettersson U., Sambrook J. Amount of viral DNA in the genome of cells transformed by adenovirus type 2. J Mol Biol. 1973 Jan;73(1):125–130. doi: 10.1016/0022-2836(73)90164-2. [DOI] [PubMed] [Google Scholar]
  13. Sambrook J., Westphal H., Srinivasan P. R., Dulbecco R. The integrated state of viral DNA in SV40-transformed cells. Proc Natl Acad Sci U S A. 1968 Aug;60(4):1288–1295. doi: 10.1073/pnas.60.4.1288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sawicki W., Baranska W., Koprowski H. Susceptibility of unfertilized and fertilized mouse eggs to simian virus 40 and Moloney sarcoma virus. J Natl Cancer Inst. 1971 Nov;47(5):1045–1051. [PubMed] [Google Scholar]
  15. Smith H. S., Gelb L. D., Martin M. A. Detection and quantitation of simian virus 40 genetic material in abortively transformed BALB-3T3 clones (mice-diploid cells-virus equivalents). Proc Natl Acad Sci U S A. 1972 Jan;69(1):152–156. doi: 10.1073/pnas.69.1.152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Sutton W. D. A crude nuclease preparation suitable for use in DNA reassociation experiments. Biochim Biophys Acta. 1971 Jul 29;240(4):522–531. doi: 10.1016/0005-2787(71)90709-x. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Varmus H. E., Weiss R. A., Friis R. R., Levinson W., Bishop J. M. Detection of avian tumor virus-specific nucleotide sequences in avian cell DNAs (reassociation kinetics-RNA tumor viruses-gas antigen-Rous sarcoma virus, chick cells). Proc Natl Acad Sci U S A. 1972 Jan;69(1):20–24. doi: 10.1073/pnas.69.1.20. [DOI] [PMC free article] [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