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PubMed2003

Introduction: what are the issues in addressing the allergenic potential of genetically modified foods?

There is growing concern among the general public and the scientific community regarding the potential toxicity of genetically modified organisms (GMOs). The use of biotechnology to enhance pest resistance or nutritional value has raised a number of fundamental questions including the consequences of insertion of reporter genes, the spread of resistance genes to surrounding plants, and the use of suicide genes to prohibit reuse of seed from engineered plants. Of particular interest is the ability of proteins from GMOs to elicit potentially harmful immunologic responses, including allergic hypersensitivity. The lack of information of the potential toxicity of these products suggests a need to identify the critical issues and research needs regarding these materials and to develop testing strategies to examine the allergenicity of these compounds.

Animals↗
PubMed2002

Use of spontaneous Epstein-Barr virus-lymphoblastoid cell lines genetically modified to express tumor antigen as cancer vaccines: mutated p21 ras oncogene in pancreatic carcinoma as a model.

Spontaneous Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (SP-LCLs) can be easily obtained from latently EBV-infected cancer patients and used as a source of antigen-presenting cells (APCs) for immunotherapy. Using point-mutated (codon 12) p21(ras) (muRas) as a model tumor antigen, we evaluated the practicability of using genetically modified SP-LCLs as cancer vaccines for patients with pancreatic cancer expressing mutated Ras (muRas). The repeated stimulation of peripheral blood mononuclear cells (PBMCs) from patients with muRas-LCLs elicited a strong, muRas-specific T cell response. A significant cytotoxic activity against EBV virus proteins or components of the expression vector was not observed. The T cells were able to recognize naturally presented muRas, as shown by their cytotoxicity against muRas (Gly-12 to Val-12 or Asp-12)-expressing tumor cells. The T cell response was mainly MHC class I restricted, and peptides containing amino acids 5 to 14 of muRas-Val-12 and muRas-Asp-12 were identified as immunogenic peptides for HLA-A2. In contrast to the situation in patients with putatively muRas-primed T cells, muRas-LCLs were not able to prime naive T lymphocytes from healthy controls. Vaccination of a pancreatic cancer patient with muRas-LCL induced muRas-specific T cells in PBMCs after 4 weeks. We conclude that genetically modified muRas-LCLs can efficiently present tumor antigens to the immune system and induce antigen-specific cytotoxic T cell responses in vitro and in vivo.

Carcinoma↗
PubMed2005

Effects on weed and invertebrate abundance and diversity of herbicide management in genetically modified herbicide-tolerant winter-sown oilseed rape.

We evaluated the effects of the herbicide management associated with genetically modified herbicide-tolerant (GMHT) winter oilseed rape (WOSR) on weed and invertebrate abundance and diversity by testing the null hypotheses that there is no difference between the effects of herbicide management of GMHT WOSR and that of comparable conventional varieties. For total weeds, there were few treatment differences between GMHT and conventional cropping, but large and opposite treatment effects were observed for dicots and monocots. In the GMHT treatment, there were fewer dicots and monocots than in conventional crops. At harvest, dicot biomass and seed rain in the GMHT treatment were one-third of that in the conventional, while monocot biomass was threefold greater and monocot seed rain almost fivefold greater in the GMHT treatment than in the conventional. These differential effects persisted into the following two years of the rotation. Bees and Butterflies that forage and select for dicot weeds were less abundant in GMHT WORS management in July. Year totals for Collembola were greater under GMHT management. There were few other treatment effects on invertebrates, despite the marked effects of herbicide management on the weeds.

Agriculture↗
PubMed2006

Effect of storage and processing on plasmid, yeast and plant genomic DNA stability in juice from genetically modified oranges.

Recombinant DNA technology is an important tool in the development of plant varieties with new favourable features. There is strong opposition towards this technology due to the potential risk of horizontal gene transfer between genetically modified plant material and food-associated bacteria, especially if genes for antibiotic resistance are involved. Since horizontal transfer efficiency depends on size and length of homologous sequences, we investigated the effect of conditions required for orange juice processing on the stability of DNA from three different origins: plasmid DNA, yeast genomic DNA and endogenous genomic DNA from transgenic sweet orange (C. sinensis L. Osb.). Acidic orange juice matrix had a strong degrading effect on plasmid DNA which becomes apparent in a conformation change from supercoiled structure to nicked, linear structure within 5h of storage at 4 degrees C. Genomic yeast DNA was degraded during exposure to acidic orange juice matrix within 4 days, and also the genomic DNA of C. sinensis suffered degradation within 2 days of storage as indicated by amplification results from transgene markers. Standard pasteurization procedures affected DNA integrity depending on the method and time used. Our data show that the current standard industrial procedures to pasteurize orange juice as well as its acidic nature causes a strong degradation of both yeast and endogenous genomic DNA below sizes reported to be suitable for horizontal gene transfer.

Beverages↗
PubMed2003

Genetically modified NT2N human neuronal cells mediate long-term gene expression as CNS grafts in vivo and improve functional cognitive outcome following experimental traumatic brain injury.

Human Ntera-2 (NT2) cells can be differentiated in vitro into well-characterized populations of NT2N neurons that engraft and mature when transplanted into the adult CNS of rodents and humans. They have shown promise as treatments for neurologic disease, trauma, and ischemic stroke. Although these features suggest that NT2N neurons would be an excellent platform for ex vivo gene therapy in the CNS, stable gene expression has been surprisingly difficult to achieve in these cells. In this report we demonstrate stable, efficient, and nontoxic gene transfer into undifferentiated NT2 cells using a pseudotyped lentiviral vector encoding the human elongation factor 1-alpha promoter and the reporter gene eGFP. Expression of eGFP was maintained when the NT2 cells were differentiated into NT2N neurons after treatment with retinoic acid. When transplanted into the striatum of adult nude mice, transduced NT2N neurons survived, engrafted, and continued to express the reporter gene for long-term time points in vivo. Furthermore, transplantation of NT2N neurons genetically modified to express nerve growth factor significantly attenuated cognitive dysfunction following traumatic brain injury in mice. These results demonstrate that defined populations of genetically modified human NT2N neurons are a practical and effective platform for stable ex vivo gene delivery into the CNS.

Animals↗
PubMed2003

Genetically modified laboratory animals--what welfare problems do they face?

In this article, we respond to public concern expressed about the welfare of genetically modified (GM) nonhuman animals. As a contribution to the debate on this subject, we attempt in this article to determine in what situations the practice of genetic modification in rodents may generate significant welfare problems. After a brief discussion of the principles of animal welfare, we focus on the problem of animal suffering and review some types of gene modifications likely to cause predictable welfare problems. In this article, we also consider suffering that may be involved in the process of generating GM animals. Finally, we discuss the role of GM animals in attempts to reduce, replace, and refine the use of animals in research.

Animal Welfare↗
PubMed2001

Stress-induced evolution and the biosafety of genetically modified microorganisms released into the environment.

This article is focused on the problems of reduction of the risk associated with the deliberate release of genetically modified microorganisms (GMMs) into the environment. Special attention is given to overview the most probable physiological and genetic processes which could be induced in the released GMMs by adverse environmental conditions, namely: (i) activation of quorum sensing and the functions associated with it, (ii) entering into a state of general resistance, (iii) activation of adaptive mutagenesis, adaptive amplifications and transpositions and (iv) stimulation of inter-species gene transfer. To reduce the risks associated with GMMs, the inactivation of their key genes responsible for stress-stimulated increase of viability and evolvability is proposed.

Adaptation, Physiological↗
PubMed2006

Transformation of Acinetobacter sp. BD413 with DNA from commercially available genetically modified potato and papaya.

AIM: To estimate the likelihood of transfer of kanamycin-resistance gene (nptII) from commercially available genetically modified (GM) plants. METHODS AND RESULTS: Acinetobacter sp. BD413 carrying a plasmid containing an inactivated nptII gene was treated with DNA derived from GM potato and GM papaya. Kanamycin-resistant transformants were obtained at a frequency of 10-30 microg(-1) DNA. Calculation of the results suggested that 6-9 x 10(4) molecules of genomic DNA from GM plants were needed to obtain one transformant. However, such transformation events were not detectable in the absence of the plasmid in the host strain. CONCLUSIONS: Acinetobacter sp. BD413 was transformed with DNA derived from GM potato and GM papaya, in the presence of an inactivated nptII gene on a plasmid. However, the frequency of such events in the natural environment on wild-type strains, while evidently low, remains unknown. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results may help to evaluate potential risks associated with the use of antibiotic-resistance determinants as genetic markers in GM plants. Complete risk assessment must consider factors other than transformation frequency alone, including the natural background of antibiotic resistance present in bacterial populations, and the spectrum and clinical use of the antimicrobial agents in question.

Acinetobacter↗
PubMed2002

Genetically modified foods, science, consumers and the media.

In contrast to the situation in the USA, where a wide range of genetically modified (GM) foods is available, in Europe very few GM products have been approved for marketing as foods, and there is widespread public concern about their safety and environmental impact. The marketing of a GM crop for food use in Europe falls under the EC novel foods regulations, and applications require the submission of an extensive dossier of information. The safety evaluation of GM foods presents considerable problems both in the conduct and interpretation of experimental studies, because conventional toxicity tests used in the evaluation of simple chemicals may not be appropriate for whole foods. To rationalise the safety evaluation process and to circumvent the difficulties in toxicological assessment of food materials, the concept of substantial equivalence has been developed. The concept is that if it can be demonstrated that the novel food is essentially similar to its conventional counterpart in terms of critical nutritional or anutritional components, then it is likely to be no more or less toxic than the latter. The possible introduction of unintended effects by the genetic modification process is particularly problematic for the safety evaluation process. The new genomic and post-genomic techniques are potentially valuable in the safety evaluation of GM foods, although they are as yet in their infancy.

Animals↗
PubMedDate not supplied

[Transplantation of genetically modified cells in the treatment of children with SCID: great hopes and recent disappointments].

Children with severe combined immunodeficiency (SCID) die within 2 years of age if untreated. The only effective treatment for SCID since 1968 is a hematopoetic stem cells (HSC) transplantation. Only 25% of patients have an HLA matched related donor, while the rest have to be transplanted with T cells depleted haploidentical parental bone marrow, unrelated bone marrow or unrelated umbilical cord blood. In many cases, however, despite a positive outcome, children are not achieving B cell reconstitution and require regular IV Ig infusion. Gene therapy with genetically modified autologous cells offers a cure with no immunological complications such as graft rejection, graft versus host disease (GVHD) or post-transplantation immunosuppressive therapy. The first gene therapy trials were introduced in 1990 for adenosine deaminase (ADA) deficient patients who had failed to respond to PEG-ADA. Since then, three clinical trials have evaluated the transplantation of ex-vivo transduced autologous haematopoietic stem cells (HSC) to treat ADA deficiency. One trial used only bone marrow HSC, a second used bone marrow plus peripheral blood T lymphocytes, and a third used umbilical cord blood HSC. These trials give promise but also define the present limitations of gene therapy. Future protocols might be adjusted according to the new observations that ADA-expressing T cells have a strong selective advantage over ADA-deficient T cells. PEG-ADA enzyme therapy might be therefore contraindicated. Another new strategy might involve moderate conditioning prior to the reinfusion of genetically modified CD34+ cells, "making space" for transplanted HSC. The first successful gene therapy was reported for treatment of X-linked severe combined immunodeficiency (SCID-X1) in Science 2000. Since then, the group at the Hopital Necker in Paris has treated 11 patients with ex-vivo gene therapy for the deficiency of the common g chain. All eleven boys are alive, however, one of them recently developed a leukaemia-like disease. This case is being investigated to determine whether the genetic manipulations of the patient's HSC could be the reason for mutagenesis and how other factors could have contributed to this unfortunate event.

Adenosine Deaminase↗
PubMedDate not supplied

Production of certified reference materials for the detection of genetically modified organisms.

Certified reference materials (CRMs) are an essenIial tool in the quality assurance of analytical measurements. They are produced, certified, and used in accordance with relevant ISO (International Organization for Standardization) and BCR (Community Bureau of Reference) guidelines. The Institute for Reference Materials and Measurements (IRMM; Geel, Belgium) has produced the first powdery genetically modified organism (GMO) CRMs in cooperation with the Institute for Health and Consumer Protection (Ispra, Italy). Until now, different weight percentages in the range of 0-5% for 4 GMOs in Europe were produced and certified: Bt (Bacillus thuringiensis)-11 and Bt-176 maize, Roundup Ready soybean, and MON810 maize. Bt-11 and Bt-176 maize and Roundup Ready soybean were produced by IRMM on behalf of Fluka Chemie AG (Buchs, Switzerland). Characterization of used base material is the first step in production and is especially important for GMO CRMs. The production of powdery GMO CRMs and methods used for production control are described. Thorough control of homogeneity and stability are essential for certification of reference materials and ensure validity of the certificate for each bottle of a batch throughout a defined shelf-life. Because production of reference materials and their maintenance are very labor- and cost-intensive tasks, the usefulness of new types of GMO CRMs must be estimated carefully.

DNA, Plant↗
PubMed2005

Food and values: an examination of values underlying attitudes toward genetically modified- and organically grown food products.

This study addresses which specific values play a role in predicting participants' attitudes toward genetically modified food (GMF) and organically grown food (OGF). The first central question is whether the attitudes towards GMF and OGF are influenced by specific values and beliefs. The second central question is whether the attitudes towards GMF and OGF are related to each other, and whether the specific values underlying these two attitudes are also related to each other. A total of 100 participants responded to the Schwartz Value Survey and two questionnaires about GMF and organically grown food. When respondents scored high on the value power (dominance, submission), they rated GMF positively and OGF more negatively. Respondents who rated the value universalism (welfare for all people and protection of nature) high, rated OGF as positive. Furthermore, the relationship between attitudes and values was mediated by beliefs. These findings imply a meaningful relationship between specific values, beliefs, and these food-related attitudes, and suggest that values might play a role in explaining attitudes toward GMF and OGF products.

Adolescent↗
PubMed2006

Farm Scale Evaluations of spring-sown genetically modified herbicide-tolerant crops: a statistical assessment.

Primary results from the Farm Scale Evaluations (FSEs) of spring-sown genetically modified herbicide-tolerant crops were published in 2003. We provide a statistical assessment of the results for count data, addressing issues of sample size (n), efficiency, power, statistical significance, variability and model selection. Treatment effects were consistent between rare and abundant species. Coefficients of variation averaged 73% but varied widely. High variability in vegetation indicators was usually offset by large n and treatment effects, whilst invertebrate indicators often had smaller n and lower variability; overall, achieved power was broadly consistent across indicators. Inferences about treatment effects were robust to model misspecification, justifying the statistical model adopted. As expected, increases in n would improve detectability of effects whilst, for example, halving n would have resulted in a loss of significant results of about the same order. 40% of the 531 published analyses had greater than 80% power to detect a 1.5-fold effect; reducing n by one-third would most likely halve the number of analyses meeting this criterion. Overall, the data collected vindicated the initial statistical power analysis and the planned replication. The FSEs provide a valuable database of variability and estimates of power under various sample size scenarios to aid planning of more efficient future studies.

Agriculture↗
PubMed2005

Studies on BN rats model to determine the potential allergenicity of proteins from genetically modified foods.

AIM: To develop a Brown Norway (BN) rat model to determine the potential allergenicity of novel proteins in genetically modified food. METHODS: The allergenicity of different proteins were compared, including ovalbumin (OVA), a potent respiratory and food allergen, bovine serum albumin (BSA), a protein that is considered to have a lesser allergenic potential, and potato acid phosphatase (PAP), a non-allergenic protein when administered to BN rats via different routes of exposure (intraperitoneally or by gavage). IgG and IgE antibody responses were determined by ELISA and PCA, respectively. An immunoassay kit was used to determine the plasma histamine level. In addition, possible systemic effect of allergens was investigated by monitoring blood pressure. RESULTS: OVA provoked very vigorous protein-specific IgG and IgE responses, low grade protein-specific IgG and IgE responses were elicited by BSA, while by neither route did PAP elicit anything. In either routes of exposure, plasma histamine level in BN rats sensitized with OVA was higher than that of BSA or PAP. In addition, an oral challenge with BSA and PAP did not induce any effect on blood pressure, while a temporary drop in systolic blood pressure in few animals of each routes of exposure was found by an oral challenge with OVA. CONCLUSION: BN rat model might be a useful and predictive animal model to study the potential allergenicity of novel food proteins.

Acid Phosphatase↗
PubMed2003

Invertebrate responses to the management of genetically modified herbicide-tolerant and conventional spring crops. I. Soil-surface-active invertebrates.

The effects of herbicide management of genetically modified herbicide-tolerant (GMHT) beet, maize and spring oilseed rape on the abundance and diversity of soil-surface-active invertebrates were assessed. Most effects did not differ between years, environmental zones or initial seedbanks or between sugar and fodder beet. This suggests that the results may be treated as generally applicable to agricultural situations throughout the UK for these crops. The direction of the effects was evenly balanced between increases and decreases in counts in the GMHT compared with the conventional treatment. Most effects involving a greater capture in the GMHT treatments occurred in maize, whereas most effects involving a smaller capture were in beet and spring oilseed rape. Differences between GMHT and conventional crop herbicide management had a significant effect on the capture of most surface-active invertebrate species and higher taxa tested in at least one crop, and these differences reflected the phenology and ecology of the invertebrates. Counts of carabids that feed on weed seeds were smaller in GMHT beet and spring oilseed rape but larger in GMHT maize. In contrast, collembolan detritivore counts were significantly larger under GMHT crop management.

Agriculture↗
PubMedDate not supplied

A genetically modified adenoviral vector exhibits enhanced gene transfer of human smooth muscle cells.

Adenoviral vector-based gene therapy is a promising approach for the treatment of restenosis postangioplasty. However, a high concentration of adenoviral vector can cause cellular activation, damage, and an enhanced immune response. One approach to solving this problem is to increase gene transfer efficiency by directing adenoviral vector entry via an alternate receptor system. We have constructed an adenoviral vector, Av9LacZ, that encodes the beta-galactosidase gene and contains a chimeric fiber protein that redirects viral vector binding to the Ad3 adenoviral receptor on the host cell. We examined the ability of Av9LacZ to transduce primary human smooth muscle cells (SMC) and found that it showed a 10- to 15-fold higher transduction efficiency when compared to the prototypic adenoviral vector currently used for preclinical and clinical studies. While both vectors were able to transduce rabbit, pig and monkey SMCs, the genetically modified vector transduced human SMC with much higher efficiency. SMC obtained from the aorta, coronary, renal, popliteal and pulmonary arteries were all efficiently transduced by Av9LacZ. Consistent with the data obtained from cultured cells, Av9LacZ also transduced fresh human arterial tissues considerably more efficiently than Av1LacZ. We conclude that the large discrepancy between transduction of animal and human cells by conventional vectors supports a cautious extrapolation of the results of in vivo animal studies to man. Furthermore, the genetically modified AV9 vector may deliver better efficacy and studies in large animal models with this vector could be more predictive of therapeutic efficacy in the treatment of human restenosis.

Adenoviridae↗
PubMedDate not supplied

Interlaboratory transfer of a real-time polymerase chain reaction assay for quantitative detection of genetically modified maize event TC-1507.

A real-time polymerase chain reaction (QPCR) assay was developed for quantitative detection of a genetically modified (GM) maize event TC-1507 and modification to conventional PCR for qualitative purposes. Sequences 5'-flanking TC-1507 full-length insert were characterized and showed multiple rearrangements involving insert and maize chloroplast fragments. The event specificity of the TC-1507 assays was based on the detection of transgene and plant rearranged sequences found to 5' flank the insertion site. They were fully specific and exhibited a limit of detection below 10 target copies, allowing consistent detection of 0.1% GM levels. The QPCR was highly linear and efficient and proved adequate for quantification of GM contents, aiming at the fulfillment of legal requirements established in the European Union (i.e., compulsory labeling of TC-1507 levels >0.9%). It satisfactorily determined TC-1507 contents on different matrixes and was successfully transferred a different laboratory.

Base Sequence↗
PubMed2005

Who does the public trust? The case of genetically modified food in the United States.

Trust is important for the perception of many types of risk, including those relating to genetically modified (GM) food. Who the public trusts in any given circumstance, however, is not well understood. In this study of public trust regarding GM food, an exploratory factor analysis with Promax rotation reveals public classification of three common institutional types-evaluators, watchdogs, and merchants. The structure of relationships among these stakeholders can act to enable or constrain public support for this new technology. Evaluators-scientists, universities, and medical professionals-are the most trusted. Watchdogs-consumer advocacy organizations, environmental organizations, and media sources-are moderately trusted. Merchants-grocers and grocery stores, industry, and farmers-are least trusted. While the federal government is seen as closest to being an evaluator, it is not highly correlated with any of the factors. The lack of trust in the organizations with the greatest resources and responsibilities for ensuring the safety of GM food should be seen as an important obstacle to the adoption of the technology.

Biotechnology↗