Safety Considerations of DNA in Food

Recombinant DNA techniques are capable of introducing genetic changes into food organisms that are more predictable than those introduced through conventional breeding techniques. This review discusses whether the consumption of DNA in approved novel foods and novel food ingredients derived from genetically modified organisms (GMOs) can be regarded as being as safe as the consumption of DNA in existing foods. It concludes that DNA from GMOs is equivalent to DNA from existing food organisms that has always been consumed with human diets. Any risks associated with the consumption of DNA will remain, irrespective of its origin, because the body handles all DNA in the same way. The breakdown of DNA during food processing and passage through the gastrointestinal tract reduces the likelihood that intact genes capable of encoding foreign proteins will be transferred to gut microflora. The review does not specifically address food safety issues arising from the consumption of viable genetically modified microorganisms but it shows that the likelihood of transfer and functional integration of DNA from ingested food by gut microflora and/or human cells is minimal. Information reviewed does not indicate any safety concerns associated with the ingestion of DNA per se from GMOs resulting from the use of currently available recombinant DNA techniques in the food chain.

[1]  M. G. Lorenz,et al.  Bacterial gene transfer by natural genetic transformation in the environment. , 1994, Microbiological reviews.

[2]  Joint Fao,et al.  Toxicological evaluation of certain food additives and contaminants , 1987 .

[3]  M. Colling,et al.  Zum Einfluß des Garens auf den Puringehalt von Lebensmitteln , 1987 .

[4]  M. Hetzer,et al.  Nuclear import of U snRNPs requires importin beta. , 1997, The EMBO journal.

[5]  W. Hammes,et al.  Evidence for natural transformation of Bacillus subtilis in foodstuffs. , 1997, FEMS microbiology letters.

[6]  Deutsches Krebsforschungszentrum,et al.  Nucleocytoplasmic Transport , 1986, Springer Berlin Heidelberg.

[7]  S. Ehrlich,et al.  Intermolecular recombination during transformation of Bacillus subtilis competent cells by monomeric and dimeric plasmids. , 1983, Plasmid.

[8]  A. Krieg,et al.  Rapid induction of mitogen-activated protein kinases by immune stimulatory CpG DNA. , 1998, Journal of immunology.

[9]  G. Foster,et al.  Plant gene isolation: principles and practice. , 1996 .

[10]  D. Helinski,et al.  Replication Control and Other Stable Maintenance Mechanisms of Plasmids , 1999 .

[11]  P. Collas,et al.  Rapid targeting of plasmid DNA to zebrafish embryo nuclei by the nuclear localization signal of SV40 T antigen. , 1997, Molecular marine biology and biotechnology.

[12]  C. Gigot Plant gene isolation: Principles and practice , 1996 .

[13]  D. Görlich,et al.  Import of DNA into mammalian nuclei by proteins originating from a plant pathogenic bacterium. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[14]  G. Venemâ,et al.  Bacillus subtilis generates a major specific deletion in pAM beta 1 , 1987, Applied and environmental microbiology.

[15]  K. Kojima Safety evaluation of disodium 5'-inosinate, disodium 5'-guanylate and disodium 5'-ribonucleotide. , 1974, Toxicology.

[16]  D. Renz,et al.  Foreign (M13) DNA ingested by mice reaches peripheral leukocytes, spleen, and liver via the intestinal wall mucosa and can be covalently linked to mouse DNA. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[17]  W. Hiatt,et al.  Aminoglycoside 3'‐phosphotransferase II (APH(3')II): Review of its safety and use in the production of genetically engineered plants , 1994 .

[18]  H. Smith,et al.  Sequence-specific DNA uptake in Haemophilus transformation. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[19]  K. Smalla,et al.  Transformation of Acinetobacter sp. Strain BD413 by Transgenic Sugar Beet DNA , 1998, Applied and Environmental Microbiology.

[20]  Christine Hupfer,et al.  Detection of the genetic modification in heat-treated products of Bt maize by polymerase chain reaction , 1998 .

[21]  B. Michel Illegitimate Recombination in Bacteria , 1999 .

[22]  D. Klinman,et al.  Contribution of CpG motifs to the immunogenicity of DNA vaccines. , 1997, Journal of immunology.

[23]  D. Renz,et al.  On the fate of orally ingested foreign DNA in mice: chromosomal association and placental transmission to the fetus , 1998, Molecular and General Genetics MGG.

[24]  A. Goffeau,et al.  The complete genome sequence of the Gram-positive bacterium Bacillus subtilis , 1997, Nature.

[25]  T. Sicheritz-Pontén,et al.  The genome sequence of Rickettsia prowazekii and the origin of mitochondria , 1998, Nature.

[26]  System to study horizontal gene exchange among microorganisms without cultivation of recipients , 1996, Molecular microbiology.

[27]  V. Citovsky,et al.  Transport of DNA into the nuclei of xenopus oocytes by a modified VirE2 protein of Agrobacterium. , 1996, The Plant cell.

[28]  H. Hotzel,et al.  PCR-based quantification of genetically modified Bt maize: single-competitive versus dual-competitive approach , 2000 .

[29]  R. Huart,et al.  Fate of exogenous DNA in Arabidopsis thaliana. Translocation and integration. , 1971, European journal of biochemistry.

[30]  Hfr Strains of Escherichia coli K-12 K , 1999 .

[31]  C. Kemp,et al.  Nutrition Abstracts and Reviews Series B: Livestock Feeds and Feeding Safety issues associated with the DNA in animal feed derived from genetically modified crops. A review of scientific and regulatory procedures , 2000 .

[32]  P. Bhargava,et al.  Uptake of nonviral nucleic acids by mammalian cells. , 1971, Progress in nucleic acid research and molecular biology.

[33]  The natural transformation of the soil bacteria Pseudomonas stutzeri and Acinetobacter sp. by transgenic plant DNA strictly depends on homologous sequences in the recipient cells. , 2001, FEMS microbiology letters.

[34]  W. Doerfler Patterns of DNA methylation--evolutionary vestiges of foreign DNA inactivation as a host defense mechanism. A proposal. , 1991, Biological chemistry Hoppe-Seyler.

[35]  K. Nielsen,et al.  Horizontal gene transfer from transgenic plants to terrestrial bacteria--a rare event? , 1998, FEMS microbiology reviews.

[36]  W. Rutter,et al.  Homology requirements for recombination in Escherichia coli. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[37]  M. Pita,et al.  Effects of dietary nucleotides upon lipoprotein pattern of newborn infants , 1986 .

[38]  W. Wackernagel,et al.  Detection of nptII (kanamycin resistance) genes in genomes of transgenic plants by marker-rescue transformation , 1998, Molecular and General Genetics MGG.

[39]  E. Raz,et al.  Immunostimulatory DNA Sequences Necessary for Effective Intradermal Gene Immunization , 1996, Science.

[40]  J. R. Bronk,et al.  The transport of pyrimidines into tissue rings cut from rat small intestine. , 1987, The Journal of physiology.

[41]  B. Erickson Gene transfer in the environment. , 2001, Environmental science & technology.

[42]  H. Yokoyama,et al.  The effects of oral RNA and intraperitoneal nucleoside-nucleotide administration on methicillin-resistant Staphylococcus aureus infection in mice. , 1993, JPEN. Journal of parenteral and enteral nutrition.

[43]  F. Käferstein Strategies for assessing the safety of foods produced by biotechnology: report on a Joint FAO/WHO Consultation , 1991 .

[44]  J. Altenbuchner,et al.  Nucleic acid and protein elimination during the sugar manufacturing process of conventional and transgenic sugar beets. , 1998, Journal of biotechnology.

[45]  H. Neve,et al.  Bacillus subtilis develops competence for uptake of plasmid DNA when growing in milk products. , 1998, Systematic and applied microbiology.

[46]  P. Dürre,et al.  Natural transfer of conjugative transposon Tn916 between gram-positive and gram-negative bacteria , 1991, Journal of bacteriology.

[47]  W. Walker,et al.  The role of nucleotides in human nutrition , 1995 .

[48]  T. Lindahl Instability and decay of the primary structure of DNA , 1993, Nature.

[49]  G. Nemerow,et al.  Nuclear Import of Adenovirus DNA in Vitro Involves the Nuclear Protein Import Pathway and hsc70* , 2000, The Journal of Biological Chemistry.

[50]  F. Rudolph,et al.  DIETARY NUCLEOTIDES, A REQUIREMENT FOR HELPER/INDUCER T LYMPHOCYTES , 1985, Transplantation.

[51]  S. Park,et al.  Integration of heterologous plasmid DNA into multiple sites on the genome of Campylobacter coli following natural transformation , 1997, Journal of Bacteriology.

[52]  D. Venema Bacillus subtilis Generates aMajorSpecific Deletion inpAM31 , 1987 .

[53]  M Mandel,et al.  Calcium-dependent bacteriophage DNA infection. , 1970, Journal of molecular biology.

[54]  M. Smith,et al.  Strategies for assessing the safety of foods produced by biotechnology—Report of a joint FAO/WHO Consultation: pp. iv + 59. Sw. fr. 11.00. WHO, Geneva, 1991. ISBN 92-4-156145-9 , 1992 .

[55]  F. Rudolph,et al.  Effect of dietary nucleotides on lymphocyte maturation. , 1986, Advances in experimental medicine and biology.

[56]  H. Hotzel,et al.  The effect of ensiling on PCR-based detection of genetically modified Bt maize , 1999 .

[57]  D. Roos,et al.  Studies on the incorporation of precursors into purine and pyrimidine nucleotides via 'de novo' and 'salvage' pathways in normal lymphocytes and lymphoblastic cell-line cells. , 1989, Biochimica et biophysica acta.

[58]  H. Neve,et al.  Evaluation of Horizontal and Vertical Gene Transfer and Stability of Heterologous DNA in Streptococcus thermophilus Isolated from Yogurt and Yogurt Starter Cultures , 1993 .

[59]  L. Henderson,et al.  Absorption and metabolism of adenine, adenosine-5'-monophosphate, adenosine and hypoxanthine by the isolated vascularly perfused rat small intestine. , 1984, The Journal of nutrition.

[60]  W. Hammes,et al.  Safety Assessment of Genetically Modified Microorganisms Applied in Meat Fermentations , 1995 .

[61]  D. Guiney Broad Host Range Conjugative and Mobilizable Plasmids in Gram-Negative Bacteria , 1993 .

[62]  W. Doerfler,et al.  Uptake of foreign DNA from the environment: the gastrointestinal tract and the placenta as portals of entry. , 1998, Wiener klinische Wochenschrift.

[63]  R. Cunningham,et al.  The enzymology of apurinic/apyrimidinic endonucleases. , 1990, Mutation research.

[64]  G. Dianov,et al.  Generation of single-nucleotide repair patches following excision of uracil residues from DNA , 1992, Molecular and cellular biology.

[65]  R. Skurray,et al.  Genetic Organization of Transfer-Related Determinants on the Sex Factor F and Related Plasmids , 1993 .

[66]  Patrice Courvalin,et al.  Functional gene transfer from intracellular bacteria to mammalian cells , 1998, Nature Biotechnology.

[67]  A. Gutman,et al.  Effect of ribomononucleotides given orally on uric acid production in man. , 1974, Advances in Experimental Medicine and Biology.

[68]  C. A. Thomas,et al.  Molecular cloning. , 1977, Advances in pathobiology.

[69]  R. Huart,et al.  Fate of Exogenous DNA in Arabidopsis thaliana , 1971 .

[70]  S. Jarvis Characterization of sodium-dependent nucleoside transport in rabbit intestinal brush-border membrane vesicles. , 1989, Biochimica et biophysica acta.

[71]  W. Doerfler,et al.  Uptake and fate of the DNA of adenovirus type 2 in KB cells. , 1975, Virology.

[72]  J. Schiemann,et al.  Bacterial communities influenced by transgenic plants , 1995 .

[73]  A. Subramanian,et al.  Nucleotide sequence and linkage map position of the genes for ribosomal proteins L14 and S8 in the maize chloroplast genome. , 1988, European journal of biochemistry.

[74]  W. Schlimme,et al.  Genetic transformation in freshwater: Escherichia coli is able to develop natural competence , 1996, Applied and environmental microbiology.

[75]  J. Heinemann,et al.  Bacterial conjugative plasmids mobilize DNA transfer between bacteria and yeast , 1989, Nature.

[76]  A. Montag,et al.  Nucleostoffe in kohlenhydratreichen Lebensmitteln , 1990 .

[77]  G. Blobel,et al.  Viral protein R regulates nuclear import of the HIV‐1 pre‐integration complex , 1998, The EMBO journal.

[78]  J. Trevors,et al.  Persistence of viruses and DNA in soil , 1997 .

[79]  Franziska Schwarz,et al.  Antibiotic resistance spread in food , 1997, Nature.

[80]  K. Nielsen,et al.  Natural transformation and availability of transforming DNA to Acinetobacter calcoaceticus in soil microcosms , 1997, Applied and environmental microbiology.

[81]  T. Lindahl,et al.  Rate of depurination of native deoxyribonucleic acid. , 1972, Biochemistry.

[82]  H. Flint,et al.  Fate of Free DNA and Transformation of the Oral Bacterium Streptococcus gordonii DL1 by Plasmid DNA in Human Saliva , 1999, Applied and Environmental Microbiology.

[83]  R. Mosley,et al.  Peripheral engraftment of fetal intestine into athymic mice sponsors T cell development: direct evidence for thymopoietic function of murine small intestine , 1992, The Journal of experimental medicine.

[84]  R. A. Woods,et al.  Utilization of dietary nucleic acid purines for nucleotide and nucleic acid synthesis in the mouse. , 1976, Canadian journal of biochemistry.

[85]  E. Lassek,et al.  [Nucleic acid components in carbohydrate-rich food]. , 1990, Zeitschrift fur Lebensmittel-Untersuchung und -Forschung.

[86]  M Dröge,et al.  Horizontal gene transfer as a biosafety issue: a natural phenomenon of public concern. , 1998, Journal of biotechnology.

[87]  M. Hetzer,et al.  Nuclear import of U snRNPs requires importin β , 1997 .

[88]  B. Decaris,et al.  Does gene horizontal transfer occur in lactic acid bacteria co-cultures? , 1998 .

[89]  D. Dubnau,et al.  Plasmid marker rescue transformation in Bacillus subtilis , 1983, Journal of bacteriology.

[90]  P. Thomsen,et al.  Species differentiation of heated meat products by DNA hybridization. , 1991, Meat science.

[91]  M. Chung,et al.  8-oxoguanine (8-hydroxyguanine) DNA glycosylase and its substrate specificity. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[92]  T. Knudsen,et al.  Developmental expression of adenosine deaminase in the upper alimentary tract of mice. , 1990, Differentiation; research in biological diversity.

[93]  R. Einspanier,et al.  The fate of forage plant DNA in farm animals: a collaborative case-study investigating cattle and chicken fed recombinant plant material , 2001 .

[94]  S. Agrawal,et al.  Antisense oligonucleotides: towards clinical trials. , 1996, Trends in biotechnology.

[95]  I. Potrykus,et al.  “Horizontal” Gene Transfer from a Transgenic Potato Line to a Bacterial Pathogen (Erwinia chrysanthemi) Occurs—if at All—at an Extremely Low Frequency , 1995, Bio/Technology.