First Author | Sheng-Fowler L | Year | 2010 |
Journal | Int J Biol Sci | Volume | 6 |
Issue | 2 | Pages | 151-62 |
PubMed ID | 20376206 | Mgi Jnum | J:309115 |
Mgi Id | MGI:6755752 | Doi | 10.7150/ijbs.6.151 |
Citation | Sheng-Fowler L, et al. (2010) Tumors induced in mice by direct inoculation of plasmid DNA expressing both activated H-ras and c-myc. Int J Biol Sci 6(2):151-62 |
abstractText | 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 microg 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. |