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Tumors Induced in Mice by Direct Inoculation of Plasmid DNA Expressing Both Activated H-ras and c-myc

  1. Author:
    Sheng-Fowler, L.
    Cai, F.
    Fu, H. Q.
    Zhu, Y.
    Orrison, B.
    Foseh, G.
    Blair, D. G.
    Hughes, S. H.
    Coffin, J. M.
    Lewis, A. M.
    Peden, K.

  2. Author Address

    [Sheng-Fowler, Li; Cai, Fang; Fu, Haiqing; Zhu, Yong; Orrison, Brian; Foseh, Gideon; Lewis, Andrew M., Jr.; Peden, Keith] US FDA, Div Viral Prod, OVRR, CBER, Bethesda, MD 20892 USA. [Blair, Don G.; Hughes, Stephen H.; Coffin, John M.] NCI, Frederick Canc Res Facil, Frederick, MD 21702 USA. [Blair, Don G.] Tufts Univ, Boston, MA 02111 USA.;Peden, K, US FDA, Div Viral Prod, OVRR, CBER, Bldg 29A,Room 3D08,29 Lincoln Dr, Bethesda, MD 20892 USA.;andrew.lewis@fda.hhs.gov keith.peden@fda.hhs.gov
    1. Year: 2010
    2. Date: Mar 29
  2. Journal: International Journal of Biological Sciences
    1. 6
    2. 2
    3. Pages: 151-162
  4. Type of Article: Article
  5. ISSN: 1449-2288
  1. Abstract:

    Vaccines contain residual DNA derived from the cells used to produce them. As part of our investigation to assess the risk of this cellular DNA, we are developing a quantitative in vivo assay to assess the oncogenicity of DNA. In an earlier study, we had generated expression plasmids for two oncogenes - human activated T24-H-ras and murine c-myc - and had shown that these two plasmids, pMSV-T24-H-ras and pMSV-c-myc, could act in concert to induce tumors in mice, although the efficiency was low. In this study, we took two approaches to increase the oncogenic efficiency: 1) both oncogene-expression cassettes were placed on the same plasmid; 2) transfection facilitators, which increase DNA uptake and expression in vitro, were tested. The dual-expression plasmid, pMSV-T24-H-ras/MSV-c-myc, is about 20-fold more efficient at tumor induction in newborn NIH Swiss mice than the separate expression plasmids, with tumors being induced with 1 mu g of the dual-expression plasmid DNA. However, none of the transfection facilitators tested increased the efficiency of tumor induction. Based on these data, the dual-expression plasmid pMSV-T24-H-ras/MSV-c-myc will be used as the positive control to develop a sensitive and quantitative animal assay that can be used to assess the oncogenic activity of DNA.

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External Sources

  1. View record in Web of Science®
  2. WOS: 000276873800004

Library Notes

  1. Fiscal Year: FY2009-2010
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