GE crops contain bacterial DNA that may be hazardous to health
Summary for laymen by PSRAST
All genetically eningeered crops contain genetic elements from bacterial DNA. They are part of the artificial genetic elements used to ensure that the inserted genes will be accepted by the genetically manipulated
organism. Also the genes for pesticide protection, like the Bacillus Thuringiensis (Bt) gene and most herbicide tolerance genes contain such DNA.
This DNA contains a genetic element (the so called "CpG motif") that stimulates the immune system to start a sequence of reactions leading to inflammation. Animal experiments have demonstrated that exposure to these genetic elements may lead to inflammation, arthritis and lymphoma (a malignant blood disease).
Furthermore, it has been demonstrated that DNA is not broken down in the gastro-intestinal tract to the extent formerly believed. Ingested DNA sequences large enough to contain whole genes have remained intact and entered the blood and tissues.
This means that there are reasons to suspect that eating GE foods may increase the risk for contracting said disorders. No research has been done to exclude this possibility.
Professor Cummins concludes: "The available evidence is sufficient to support a moratorium on the massive intake of GM crops by human populations until the genetic consequences are resolved in the laboratory."
This is just one of a number of potentially serious hazards that have been neglected in the safety evaluation of GE foods. It is absurd that GE foods have been on the market without proper safety evaluation, see also Inadequate GE food safety assessment. [EL] It is seriously irresponsible to allow them to be sold without careful labelling.
See also our open letter [ML] demanding withdrawal of GE foods from the market.
Below you find the scientific article about the DNA CpG motif hazard.
The fate of food genes and the DNA CpG motif and its impact
Toxicology Symposium, University of Guelph
March 3, 2001
Dr. Joe Cummins, Emeritus Professor of Genetics, University of Western Ontario, Canada
In evaluating the safety of genetically modified (GM) food crops it has previously been assumed that food is completely digested and the genes of the food organisms are not circulated to the cells of the predator. However, that assumption was not tested until quite recently and found to be deficient. Gene fragments from the food are circulated and sometimes integrated into the chromosomes of the predator. Similarly, the products of genes on the DNA of bacteria (principally proteins but sometimes RNA) governed how the bacterium interacted with the animal host.
However, it was recently discovered that the DNA sequence motifs serve as important signals that allow animals to recognize the genes of bacterial pathogens and turn on inflammation defenses. GM crops all contain bacterial DNA from the plasmids used in engineering their construction.
Today I will focus on the fate of genes in GM crops and their potential ability to alter and activate the immune system.
Fate of food DNA
Evaluation of the safety of genetically modified (GM) crops seems to be hampered by the unwillingness of regulators recognize and to evaluate the impact of genetic effects that are outside simplistic models of genes and their behavior. It has been presumed that the organism destroys food genes during digestion and excretion. However, studies on DNA immunization showed that DNA could be delivered to the immune system through oral uptake. A few daring German researchers have also explored the fate of orally ingested genetic material. The papers below show that ingested DNA is not only circulated through the animal body but may be associated with nucleus and chromosomes.
The first paper "The fate of forage DNA in farm animals" by Einspanier et al (2001), studies ingestion of maize DNA and of GM maize DNA, while the second is an earlier study "On the fate of foreign DNA in mice" by Shubbert et al (1998) that showed that ingested DNA from a bacterial virus or from a plasmid transgene is incorporated in chromosomes and is passed from mother to fetus. The authors of the study ask "is maternally ingested foreign DNA a potential mutagen for developing fetus?" If food DNA sequences are randomly incorporated into coding sequences including introns, exons or promoters they will certainly act as mutagens.
These two studies show that food DNA is circulated to the tissues of animals and may even be transmitted from the mother to the fetal tissues. Studies of the type described above should be repeated and extended. Mainly, however, the studies should stand out as a clear warning to regulators that they cannot ignore a major paradigm shift in the way that DNA and genes evaluated.
In one of the two studies transgenic DNA from a plasmid is clearly circulated to tissues while in the other transgenic DNA was not detected in tissues. However, the latter study involved a lower relative input of the transgene and should be repeated with higher resolution of the transgene and using high relative input of the transgene say by feeding concentrated Bt plasmid. Experiments of that type can be undertaken using human volunteers as well as farm and experimental animals.
The available evidence is sufficient to support a moratorium on the massive intake of GM crops by human populations until the genetic consequences are resolved in the laboratory. It is not sane to suggest that the huge populations fed unlabeled GM crops are a sufficient test of the safety of the genetic constructions. No method is available to readily quantify the intake and exposure of humans to unlabeled GM foods.
The impact of bacterial DNA on the immune system (the CpG effect)
Essentially all of the GM crops marketed or being field tested presently contain bacterial sequences as a part of the plasmids used for delivering genes and many of the primary crop protection genes are of bacterial origin. Such genes include Bt and most herbicide tolerance genes.
DNA vaccines have generated a huge literature and clinical applications showing the activity and cellular incorporation of DNA administered by oral, inhalation, injection, vaginal or dermal application (Molling 1997,Donnoley et al 1997 and Gurunathan et al 2000). Ingestion of bacteria does not appear to be an effective means of delivering DNA because the bacterial cell walls effectively contain the nucleic acid (for example, in yogurt the milk products are digested but the bacteria of the culture are passed intact). Lysis genes have been found necessary and effective in triggering release of DNA for mucosal vaccine delivery (Jani and Mekalanos 200). In contrast , the crops eaten by animals release oligonucleotides and DNA peptide complexes during digestion and such molecules circulate to a significant degree.
The bacterial genes used in constructing GM crops have a property that impacts on the immune system over and above the ability to produce antibodies. Eukaryote DNA has relatively low frequencies of the dinuleotide motif CpG and that motif is methylated and plays a role in gene regulation while bacteria and their viruses have a high frequency of the CpG motif that is usually unmethylated.
Apparently the CpG motif in DNA molecules and oligonucleotides provides a signal that the immune system recognizes and initiates a primary sequence of reactions leading to activation of the immune system leading to inflammation (Manders and Thomas 2000 and Gurunathan et al 2000). Gung et al (1999) found that bacterial DNA CpG caused septic arthritis. Hemmi et al (2000) found that there is a receptor protein that recognizes bacterial DNA. Oligonucleotides rich in the CpG motif are used to enhance immunization. Inflammation is an essential part of the immune response but it adversely affects existing conditions such as autoimmune disease. Furthermore, it has been found that CpG oligonucleotides rescue B cell lymphoma cells from anti-IgM mediated growth inhibition (Han et al 1999). The oligonucleotide acts as a promoter of lymphoma.
Finally, Gorecki and Simons (1999) pointed out a danger to the fetus in DNA vaccination of the mother. That danger was the creation of tolerance in the fetus leading to individuals more susceptible to infection and/or they may become carriers. The introduction of genes with bacterial CpG motif to the fetus is likely to have untoward consequences.
In conclusion, the bacterial genes used in GM crops have been found to have significant impacts on the individuals ingesting GM crops. The impacts include inflammation, arthritis and lymphoma promotion. The consequence of GM food genes being incorporated into the chromosomes of somatic cells of those consuming GM food and their unborn has been ignored by those charged with evaluating the hazards of GM crops.
Deng G, Nilsson A, Verdrengh M, Collins L, Tarkowski A "intra-articularly located bacteria containging CpG motifs induces arthritis" 1999 Nature Medicine 5,702-6
Donnelly J,Ulmer U,Shiver J and Lui M. "DNA Vaccines"1997 Annu Rev Immunol 15,617-48
Einspanier R, Klotz A, Kraft J et al (2001). European Food Research and Technology Abstract Volume 212 Issue 2 (2001) pp 129-134 The fate of forage plant DNA in farm animals: a collaborative case-study investigating cattle and chicken fed recombinant plant material
Gorecki D and Simons J "The dangers of DNA vaccination" 1999 Nature Medicine 5,126
Guunathan S, Klinman D and Seder R. "DNA Vaccines" 2000 Annu Rev. Immunol 18,927-74
Hemmi H,Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, Matsumoto M, Hoshino K, Wagner H, Takeda K, Akira,S "A Toll-like receptor recognizes bacterial DNA"2000 Nature 408, 740 - 745
Hsu S, Chung S, Robertson D, Ralph L, Chelvarajan R, Bondada S (1999) "CpG oligodeoxynucleotides rescue BKS-2 immature B cell lymphoma from anti-Ig-M-mediated growth inhibition by up-regulating of egr-1" International Immunology 6,871-9
Jain V and Mekalanos J "Use of lambda phage S and R gene products in an inducible lysis system from Vibrio cholerae and Salmonella enterica servovar Typhimurium-Based vaccine delivery systems" (2000) Infection and Immunity 68,986-9
Manders P and Thomas R "Immunology of DNA vaccines: CpG motifs and antigen presentation" Inflamm Res 49,199-205
Molling K "Naked DNA for vaccine or therapy" (1997) JMolMed 75,242-6
Schubbert R, Hohlweg U, Renz D and Doerfler W (1998). "On the fate of orally ingested foreign DNA in mice: chromosomal association and placental transmission to the fetus" (1998) Mol Gen Genet 259: 569-576
Schubbert R,Renz D, Schmitz B and Doerfler W, "Foreign (M13) DNA ingested by mice reaches peripheral leucocytes, spleen,and liver via the intestinal wall mucosa and can be covalently linked to mouse DNA" (1997) Proc. Natnl Acad Sci USA 94,961-6
"Genetically Engineered Food - Safety Problems"Published by PSRAST
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