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Cited by 11Carcinogens and Genotoxicity AssessmentImmunotherapy and Immune ResponsesCancer-related Molecular Pathways

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

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Sheng-Fowler, Li, Cai, Fang, Fu, Haiqing, Zhu, Yong, Orrison, Brian, Foseh, Gideon, Blair, Don G., Hughes, Stephen H. +3 more·2010·International Journal of Biological Sciences
DOI 10.7150/ijbs.6.151PMC PMC2850538
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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 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.

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  • Residual host cell DNA (rcDNA) from continuous cell lines used for manufacturing biological medicinal products has been considered a safety risk.

    “Residual host cell DNA (rcDNA) from continuous cell lines used for manufacturing of biological medicinal products has been considered as safety risk.”

    From Comparative analysis of the performance of residual host cell DNA assays for viral vaccines produced in Vero cells (2019) · cites this paper as Sheng-Fowler et al., 2010

    The Introduction (page not available in our copy) says residual DNA from cells used to produce viral vaccines has been considered a potential safety risk, particularly when the cells are tumorigenic or derived from tumors. It does not extend that assessment to biological medicinal products generally or specifically identify continuous cell lines as the source of the risk. (LLM, conf=0.85)

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  • The main risks associated with rcDNA in viral vaccines are infectivity and oncogenicity.

    “The main risks associated with rcDNA in viral vaccines are infectivity and oncogenicity; rcDNA might be capable of transmitting viral infections if retroviral proviruses, integrated copies of DNA viruses, or extra chromosomal genomes are present (FDA, 2010;Sheng-Fowler et al., 2009), or may pose a potential risk for oncogenesis if viral or cell substrate (derived from tumors or which are tumorigen”

    From Comparative analysis of the performance of residual host cell DNA assays for viral vaccines produced in Vero cells (2019) · cites this paper as Sheng-Fowler et al., 2010

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Research works printed but not linked: 37

  1. [1]Hilleman MR Cells, vaccines, and the pursuit of precedent Natl Cancer Inst Monogr 1968 29 463 469 4888933
  2. [2]Hilleman MR Line cell saga - an argument in favor of production of biologics in cancer cells Adv Exp Med Biol 1979 118 47 58 227236
  3. [3]Petricciani JC Horaud FN DNA, dragons and sanity Biologicals 1995 23 233 238 8527124
  4. [4]Petricciani JC Regan PJ Risk of neoplastic transformation from cellular DNA: calculations using the oncogene model Dev Biol Stand 1987 68 43 49 3480254
  5. [5]Petricciani J Loewer J An overview of cell DNA issues Dev Biol 2001 106 275 282 11761240
  6. [6]Lewis AMJr Krause P Peden K A defined-risks approach to the regulatory assessment of the use of neoplastic cells as substrates for viral vaccine manufacture Dev Biol 2001 106 513 535 11761266
  7. [7]Bishop JM Baker B Fujita D Genesis of a virus-transforming gene Natl Cancer Inst Monogr 1978 48 219 223 219354
  8. [8]Land H Parada LF Weinberg RA Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes Nature 1983 304 596 602 6308472
  9. [9]Santos E Pulciani S Barbacid M Characterization of a human transforming gene isolated from T24 bladder carcinoma cells Fed Proc 1984 43 2280 2286 6325252
  10. [10]Bos TJ Oncogenes and cell growth Adv Exp Med Biol 1992 321 45 99 1333167
  11. [11]Thompson TC Southgate J Kitchener G Land H Multistage carcinogenesis induced by ras and myc oncogenes in a reconstituted organ Cell 1989 56 917 930 2538247
  12. [12]Ledwith BJ Manam S Troilo PJ Plasmid DNA Vaccines: Investigation of Integration into Host Cellular DNA following Intramuscular Injection in Mice Intervirology 2000 43 258 272 11251381
  13. [13]Kurth R Risk potential of the chromosomal insertion of foreign DNA Ann N Y Acad Sci 1995 772 140 151 8546386
  14. [14]Kurth R Risk potential of the chromosomal insertion of foreign DNA Dev Biol Stand 1998 93 45 56 9737376
  15. [15]Doehmer J Residual cellular DNA as a potential transforming factor Dev Biol Stand 1987 68 33 41 3480253
  16. [16]Löwer J Risk of tumor induction in vivo by residual cellular DNA: quantitative considerations J Med Virol 1990 31 50 53 2198328
  17. [17]Temin HM Overview of biological effects of addition of DNA molecules to cells Dev Biol Stand 1998 93 37 44 9737375
  18. [18]Griffiths E Major issues associated with the use of cell substrates for the production of vaccines Dev Biol 2001 106 25 35 11761238
  19. [19]Barrett JC Mechanisms of multistep carcinogenesis and carcinogen risk assessment Environ Health Perspect 1993 100 9 20 PMC1519586 8354184
  20. [20]Fearon ER Genetic alterations underlying colorectal tumorigenesis Cancer Surv 1992 12 119 136 1638544
  21. [21]Hennings H Glick AB Greenhalgh DA Critical aspects of initiation, promotion, and progression in multistage epidermal carcinogenesis Proc Soc Exp Biol Med 1993 202 1 8 8424089
  22. [22]Pitot HC The molecular biology of carcinogenesis Cancer 1993 72 962 970 8334671
  23. [23]Hesketh R The Oncogene and Tumour Suppressor Gene FactsBook. Second Edition London Academic Press 1997
  24. [24]Kondoh H Lleonart ME Gil J Glycolytic enzymes can modulate cellular life span Cancer Res 2005 65 177 185 15665293
  25. [25]Davé UP Jenkins NA Copeland NG Gene therapy insertional mutagenesis insights Science 2004 303 333 14726584
  26. [26]Costinean S Zanesi N Pekarsky Y Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice Proc Natl Acad Sci U S A 2006 103 7024 7029 PMC1459012 16641092
  27. [27]Dalmay T MicroRNAs and cancer J Intern Med 2008 263 366 375 18298485
  28. [28]Fabbri M Croce CM Calin GA MicroRNAs Cancer J 2008 14 1 6 18303474
  29. [29]Voorhoeve PM Agami R Classifying microRNAs in cancer: the good, the bad and the ugly Biochim Biophys Acta 2007 1775 274 282 17189674
  30. [30]Wiemer EA The role of microRNAs in cancer: no small matter Eur J Cancer 2007 43 1529 1544 17531469
  31. [31]Cowland JB Hother C Gronbaek K MicroRNAs and cancer Apmis 2007 115 1090 1106 18042145
  32. [32]Sheng L Cai F Zhu Y Oncogenicity of DNA in vivo: Tumor induction with expression plasmids for activated H-ras and c-myc Biologicals 2008 36 184 197 18218323
  33. [33]Kohl NE Ruley HE Role of c-myc in the transformation of REF52 cells by viral and cellular oncogenes Oncogene 1987 2 41 48 2830582
  34. [34]Ruley HE Transforming collaborations between ras and nuclear oncogenes Cancer Cells 1990 2 258 268 2223387
  35. [35]Land H Chen AC Morgenstern JP Parada LF Weinberg RA Behavior of myc and ras oncogenes in transformation of rat embryo fibroblasts Mol Cell Biol 1986 6 1917 1925 PMC367729 3785184
  36. [36]Small MB Hay N Schwab M Bishop JM Neoplastic transformation by the human gene N-myc Mol Cell Biol 1987 7 1638 1645 PMC365263 3299052
  37. [37]Zerlin M Julius MA Cerni C Marcu KB Elevated expression of an exogenous c-myc gene is insufficient for transformation and tumorigenic conversion of established fibroblasts Oncogene 1987 1 19 27 3325875

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Authors
Sheng-Fowler, L., Cai, F., Fu, H., Zhu, Y., Orrison, B., Foseh, G., Blair, D. G., Hughes, S. H., Coffin, J. M., Lewis Jr, A. M., & Peden, K.
Affiliations
  • Center for Biologics Evaluation and Research (US)
  • National Institutes of Health (US)
  • Tufts University (US)
  • Frederick National Laboratory for Cancer Research (US)
  • Center for Drug Evaluation and Research (US)
Corresponding author
Peden, Keith
ORCID
Venue
International Journal of Biological Sciences
Publisher
Ivyspring International Publisher
Published
2010
Volume
6
Issue
2
Pages
151-162
ISSN
1449-2288 (ISSN-L)
DOI
10.7150/ijbs.6.151
PMC
PMC2850538
OpenAlex
W2120370890
Cited by
11
References
0
Citations by year
2025: 1 · 2024: 1 · 2023: 1 · 2020: 1 · 2019: 1 · 2016: 2 · 2014: 3 · 2013: 1
FWCI
0.10
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • International Journal of Biological Sciences (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • American Cancer Society
  • James N. Kirby Foundation
  • National Institutes of Health
  • National Cancer Institute
  • National Institute of Allergy and Infectious Diseases
  • Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords
c-Myc, DNA uptake, NIH Swiss mice, oncogenes
MeSH terms
Animals, DNA, Humans, Mice, Inbred C57BL, Neoplasms, Oncogenes, Plasmids, Transfection, Gene Expression Regulation, Neoplastic, Polymerase Chain Reaction, Proto-Oncogene Proteins c-myc, ras Proteins, NIH 3T3 Cells, Mice, Rats

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