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Common Plant Vector Injects Genes into Human Cells
by Joseph Cummins, Department of Plant Sciences,
University of Western Ontario
Agrobacterium tumefaciens is a bacterium that causes tumors to appear on the stems of infected plants. The bacterium causes the tumors by transferring genes to the cells of the infected plant from a tumor-inducing plasmid (Ti). The Ti plasmid has virulence genes that determine attachment to cells and transfer of a segment of the plasmid, T-DNA, to the plant cell. The transferred DNA is integrated essentially randomly (no apparent sequence bias at the site of insertion) into the plant chromosomes and normally adds bacterial genes that stimulate plant tumor cell growth.
In crop genetic manipulation (GM), the growth-stimulating genes that give rise to tumors are replaced by GM constructs which include genes for antibiotic resistance, viral promoters and genes for desired crop traits such as herbicide tolerance.
Until quite recently, the genetic engineering community has assumed that Agrobacterium does not infect animal cells, and certainly would not transfer genes into them. But this has been proved wrong.
A paper published earlier this year reports that T-DNA can be transferred to the chromosomes of human cancer cells. (1) In fact, Agrobacterium attaches to and genetically transforms several types of human cells. The researchers found that in stably transformed HeLa cells, the integration event occurred at the right border of the Ti plasmid’s T-DNA, exactly as would happen when it is being transferred into a plant cell genome. This suggests that Agrobacterium transforms human cells by a mechanism similar to that which it uses for transformation of plant cells.
Agrobacterium attaches to and genetically transforms several types of human cells.
The paper shows that human cancer cells along with neuron and kidney cells were transformed with the Agrobacterium T-DNA. Such observations should raise alarm for those who use Agrobacterium in the laboratory.
The integrated T-DNA will almost certainly act as a mutagen as it integrates into human chromosomes. Cancer can be triggered by activation of oncogenes (cancer genes) or inactivation of cancer-suppressing genes. Furthermore, the sequences carried within the T-DNA in the transforming bacterium can be expressed in the transformed cells (the viral promoter CaMV has been found to be active in HeLa cells (2)) and constructions currently being tested include pharmaceutically active human genes such as the interleukins. (3)
It is clear that little has been done to prevent environmental escape of the transforming bacteria or to quantify such releases. In conclusion, a study of cancer incidence among those exposed to Agrobacterium tumefaciens in the laboratory and in the field is needed. It would be worthwhile to screen workers for T-DNA sequences.
Notes
1. Kunik T, Tzfira T, Kapulnik Y, Gafni Y, Dingwall C, and Citovsky V. Genetic transformation of HeLa cells by Agrobacterium. PNAS USA, 2001, 98, 1871-87.
2. Ho MW, Ryan A and Cummins J. CaMV 35S promoter fragmentation hotspot confirmed and it is active in animals. Microbial Ecology in Health and Disease, 2000, 12, 189. http://www.i-sis.org/mehd3.shtml
3. See “GM AIDS virus more deadly” by Joe Cummins & Mae-Wan Ho. ISIS Report, July 19, 2001 http://www.i-sis.org/GM_aids_virus.shtml
For more details contact jcummins@uwo.caSee the I-SIS website at http://www.i-sis.org/