The genetic engineering community has assumed that Agrobacterium, a commonly used gene transfer vector for plants, does not infect animal cells, and certainly would not transfer genes into them. But this has been proved wrong. Prof. Joe Cummins warns of hazards to laboratory and farm workers.
Agrobacterium tumefaciens is a bacterium that causes tumours to appear on the stems of infected plants. The bacterium causes the tumours by transferring genes to the cells of the infected plant cells from a tumour 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 add bacterial genes that stimulate plant tumour cell growth.
In crop genetic manipulation (GM), the growth-stimulating genes that give rise to tumours are replaced by GM constructs which include genes for antibiotic resistance, plant 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 plants 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 (ie, 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.
Article first published 23/09/01
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