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PubMed2000

Role of antimutagens/anticarcinogens in cancer prevention.

Recently it has become increasingly clear that chemicals found in our foods and beverages can prevent the genetic damage that leads to cancer initiation. Such substances may also affect subsequent events in the pathways that lead to cancer, and may have the potential to inhibit the mutations that allow tumor cells to become resistant to antitumor agents. We describe here the antimutagenic potential of Glabrene analogs against EMS-induced mutations utilizing modified Ames tests in S. typhimurium TA 100 and E. coli JC 5088. Results of studies of the ability of well-known antioxidants such as EGCG and related compounds to prevent drug resistance mutations in microorganisms are described, and their possible significance in the prevention of chemotherapeutic drug-resistance in tumor cells is discussed.

Anticarcinogenic Agents↗
PubMed1996

Novel lantibiotics and their pre-peptides.

In recent years there has been a considerable increase in studies of bactericidal peptides produced by Gram-positive bacteria, with particular emphasis upon their potential application as food preservatives. A number of these peptides contain lanthionine and other post-translationally modified amino acid residues. The lanthionine-containing molecules (lantibiotic) appear to have evolved in two quite different lineages, type A and type B. This mini-review introduces the reader to several of the more recently described type A lantibiotics for which relatively detailed biochemical and/or genetic data has already been gathered. A wider diversity of compounds of type A lantibiotics has been described in the recent years. Novel features of some of the more recently described type A lantibiotics to be reported in this review include: a) New modifications such as D-Ala and 2-hydroxypropionyl residues, both derived from serine. b) Different types of pre-lantibiotic leader sequences. c) The apparent requirement for different numbers and types of genes for synthesis of some active type A lantibiotics. d) Cytolysin functions as both a hemolysin and a bacteriocin. e) One of the newly-described lantibiotics (lactocin S) does not have any net charge at neutral pH another (carnocin UI49) is the largest of the lantibiotics discovered and the killing action of another (cytolysin) has been shown to be depend on the interaction of two peptides.

Alanine↗
PubMed1996

Considerations in miniaturizing simplified agro-ecosystems for advanced life support.

Miniaturizing the Earth's biogeochemical cycles to support human life during future space missions is the goal of the NASA research and engineering program in advanced life support. Mission requirements to reduce mass, volume, and power have focused efforts on (1) a maximally simplified agro-ecosystem of humans, food crops, and microbes; and, (2) a design for optimized productivity of food crops with high light levels over long days, with hydroponics, with elevated carbon dioxide and other controlled environmental factors, as well as with genetic selection for desirable crop properties. Mathematical modeling contributes to the goals by establishing trade-offs, by analyzing the growth and development of experimental crops, and by pointing to the possibilities of directed phasic control using modified field crop models to increase the harvest index.

Agriculture↗
PubMed2006

Transformation of the green alga Haematococcus pluvialis with a phytoene desaturase for accelerated astaxanthin biosynthesis.

Astaxanthin is a high-value carotenoid which is used as a pigmentation source in fish aquaculture. Additionally, a beneficial role of astaxanthin as a food supplement for humans has been suggested. The unicellular alga Haematococcus pluvialis is a suitable biological source for astaxanthin production. In the context of the strong biotechnological relevance of H. pluvialis, we developed a genetic transformation protocol for metabolic engineering of this green alga. First, the gene coding for the carotenoid biosynthesis enzyme phytoene desaturase was isolated from H. pluvialis and modified by site-directed mutagenesis, changing the leucine codon at position 504 to an arginine codon. In an in vitro assay, the modified phytoene desaturase was still active in conversion of phytoene to zeta-carotene and exhibited 43-fold-higher resistance to the bleaching herbicide norflurazon. Upon biolistic transformation using the modified phytoene desaturase gene as a reporter and selection with norflurazon, integration into the nuclear genome of H. pluvialis and phytoene desaturase gene and protein expression were demonstrated by Southern, Northern, and Western blotting, respectively, in 11 transformants. Some of the transformants had a higher carotenoid content in the green state, which correlated with increased nonphotochemical quenching. This measurement of chlorophyll fluorescence can be used as a screening procedure for stable transformants. Stress induction of astaxanthin biosynthesis by high light showed that there was accelerated accumulation of astaxanthin in one of the transformants compared to the accumulation in the wild type. Our results strongly indicate that the modified phytoene desaturase gene is a useful tool for genetic engineering of carotenoid biosynthesis in H. pluvialis.

Biotechnology↗
PubMed2002

An alternative focus in strategic research on disease vectors: the potential of genetically modified non-biting mosquitoes.

We examine the constraints and the feasibility of field experiments involving the release of genetically modified (GM) pathogen-resistant mosquitoes, and whether there are alternatives to the research line based on the production of refractory strains. The production of a GM mosquito strain characterized instead by obligate primiparous and parous autogeny and by disrupted host seeking and biting behaviour could make the release more acceptable by the general public. Genetic transformation should act in this case to reverse some of the essential steps of the evolutionary process that gave rise to hematophagy. The replacement strategy could be based on the mass release of both sexes in a well defined ecological niche made temporarily empty of the natural population, thus avoiding the problems related to the need of sexual competitiveness of the released material. This option is encouraged by the growing evidence that competitive exclusion mechanisms influence the pattern of distribution of different taxa within Anopheles gambiae s.s. and by the fact that the plesiomorphic characteristics of vitellogenesis without a blood meal (autogeny), which exploits fat body reserve accumulated during larval life and food other than blood in adult life, persist as genetic variants in various hematophagous insect groups, and it has been found secondarily fixed in others showing stable reversions to primiparous and parous autogeny. If this has been the result of natural selection, then the artificial production of non-biting mosquito strains, by selection and/or transgenesis, should be feasible.

Animals↗
PubMed2005

Plasma homocysteine levels in patients with type 2 diabetes in a Mediterranean population: relation with nutritional and other factors.

BACKGROUND AND AIM: Hyperhomocysteinemia is a major and independent risk factor for atherothrombotic vascular disease. It may be promoted by genetic factors, nutritional deficiencies of the vitamin cofactors required for homocysteine metabolism, and other modifiable factors. This cross-sectional study investigated the effect of dietary habits and lifestyle on plasma total homocysteine (tHcy) levels in patients with type 2 diabetes in a Mediterranean population. METHODS AND RESULTS: A total of 126 diabetic and 76 healthy subjects were interviewed using a food-frequency questionnaire. Information consisted of dietary and smoking habits, coffee and alcohol consumption and physical activity recording, during the month prior to enrollment. Measurements included blood pressure, body mass index (BMI), waist-to-hip ratio (WHR), plasma tHcy, folate, vitamin B12, lipids, HbA(1c), creatinine, uric acid, and glomerular filtration rate (GFR). Plasma tHcy levels were not different between diabetic and control subjects (11.49+/-3.68 vs 12.67+/-3.79 micromol/l respectively, P = 0.40). Diabetic subjects had significantly higher plasma folate levels and consumed more fish, fruit and vegetables, in comparison with controls. Controls consumed more red meat, coffee, and alcohol. Multivariate analysis in diabetic subjects, after controlling for age, sex, systolic blood pressure, duration of diabetes, GFR, plasma uric acid levels, and the amount of the weekly consumption of fruit and vegetables, demonstrated that age, GFR and the weekly amount of fruit and vegetable consumption were independently associated with plasma tHcy concentrations [regression coefficient (B) = 0.11, SE (B) = 0.03, P = 0.001, B = -0.07, SE (B) = 0.01, P < 0.0001, and B = -0.05, SE (B) = 0.02, P = 0.04, respectively]. The weekly amount of coffee, alcohol and red meat consumption, and physical activity level were not related with plasma tHcy levels in either study group. CONCLUSIONS: 1) Plasma tHcy levels were not different in the diabetic group as compared to the control group. 2) In patients with type 2 diabetes age, GFR and the consumption of fruit and vegetables were strong and independent determinants of plasma tHcy levels.

Adult↗
PubMed2026

CRISPR/Cas9-Mediated Editing of Bsr-d1 and Pi21 Enhances Blast Resistance in a High-Quality Rice Maintainer Line.

Rice (Oryza sativa L.) is a staple food crop worldwide, and improving disease resistance is a core target in rice breeding. In this study, we employed CRISPR/Cas9 genome editing to modify the coding sequence (CDS) of two susceptibility genes, Bsr-d1 and Pi21, in the elite maintainer line Gengxiang B to enhance its blast resistance. We generated Bsr-d1/Pi21 double homozygous mutants via Agrobacterium-mediated genetic transformation. Quantitative RT-PCR revealed significantly suppressed transcript accumulation of both target genes in the edited lines compared with the wild type Gengxiang B. Upon inoculation with Magnaporthe oryzae, multiple defense-related marker genes were markedly upregulated in the double mutants. Phenotypic assays demonstrated significantly reduced disease severity for both leaf and panicle blast in the edited lines compared with the wild type. Importantly, no statistically detectable differences were found between the double mutants and wild-type plants for key agronomic or grain quality traits. Collectively, these results demonstrate that CRISPR/Cas9-mediated editing of susceptibility loci generates genetically stable blast-resistant rice germplasm without compromising agronomic traits or grain quality, providing valuable genetic resources for future rice varietal improvement.

Bsr-d1↗
PubMed1998

Breast cancer risk, meat consumption and N-acetyltransferase (NAT2) genetic polymorphisms.

Although inconsistencies exist, some studies have shown that meat consumption is associated with breast cancer risk. Several heterocyclic amines (HAs), formed in the cooking of meats, are mammary carcinogens in laboratory models. HAs are activated by polymorphic N-acetyltransferase (NAT2) and rapid NAT2 activity may increase risk associated with HAs. We investigated whether ingestion of meat, chicken and fish, as well as particular concentrated sources of HAs, was associated with breast cancer risk, and if NAT2 genotype modified risk. Caucasian women with incident breast cancer (n = 740) and community controls (n = 810) were interviewed and administered a food frequency questionnaire. A subset of these women (n = 793) provided a blood sample. Polymerase chain reaction and restriction fragment length polymorphism analyses were used to determine NAT2 genotype. Consumption of red meats, as well as an index of concentrated sources of HAs, was not associated with increased breast cancer risk, nor did risk vary by NAT2 genotype. In post-menopausal women, higher fish consumption was inversely associated with risk (odds ratio = 0.7; 95% confidence interval, 0.4-1.0); among pre-menopausal women, there was the suggestion of inverse associations between risk and pork and chicken intake. Our results suggest that consumption of meats and other concentrated sources of HAs is not associated with increased breast cancer risk. However, due to the strong biologic plausibility for a role of some HAs in mammary carcinogenesis, and the likely measurement error in evaluation of sources of HAs in this study, further studies of these possible relationships are warranted.

Amines↗
PubMed2002

Genetically modified industrial yeast ready for application.

Tremendous progress in the genetic engineering of yeast had been achieved at the end of 20th century, including the complete genome sequence, genome-wide gene expression profiling, and whole gene disruption strains. Nevertheless, genetically modified (GM) baking, brewing, wine, and sake yeasts have not, as yet, been used commercially, although numerous industrial recombinant yeasts have been constructed. The recent progress of genetic engineering for the construction of GM yeast is reviewed and possible requirements for their application are discussed. 'Self-cloning' yeast will be the most likely candidate for the first commercial application of GM microorganisms in food and beverage industries.

Journal Article↗
PubMed2004

[Immunotoxicologic assessment of transgenetic rice].

OBJECTIVE: To assess the immunotoxicologic aspect of transgenetic plant. METHODS: BALB/C mice were fed with food composed by transgenic rice (into which cowpea trypsin inhibitor gene was introduced) or nontransgenetic rice (which has the same gene composition as the transgenic rice except for the cowpea trypsin inhibitor gene) for 30 days. All food is made according to the composition of AIN-93G. In the end, all kinds of immunotoxicologic indexes of mice of every group were compared such as body weight, guts index, blood routine test, lymphocyte sort, serum antibody titter, plaque forming cell, delayed hypersensitivity response, macrophage function test. RESULTS: All immunotoxicologic indexes of mice fed either by transgenic rice or nontransgenetic rice have no differences to those of mice fed by normal food. CONCLUSION: Transgenic rice is substantially equivilent to nontransgenetic rice in immunotoxicologic aspect.

Animals↗
PubMed1999

[Elements of epidemiology and initiation of carcinogenesis in carcinomas of the upper aerodigestive tract. Future therapeutic consequence?].

The study of epidemiology and of the carcinogenesis in epidermoid carcinomas of the upper aerodigestive tract shows that their occurrence is not random. Tobacco abuse plays a major role, especially because of benzopyrene, mutagen of the P53 gene, however it is associated with many other potentiating factors: alcohol, metals, hydrocarbures, virus, food, climate, genetic fragility that create genetic lesions at the origin of carcinogenesis. The latter occurs as "field cancerization" with multiple alterations of the mucosa and general attack of the control systems of the differentiation, growth and cell apoptosis which usually protect the cell against the phenomena of carcinogenesis. The P53 protein gene, retinoid receptors as well as the system of detoxifying glutathion S transferase are modified at the very early stage of these diseases, these abnormalities can be logically related to epidemiological data. These data lead us therefore to imagine complementary specific reverting therapies of induced genetic abnormalities, through the reexpression of non mutated gene encoding P53 protein and the use of retinoid. These various modalities are reported hereafter.

Age Factors↗
PubMed2003

Genetic manipulation of Lactococcus lactis by using targeted group II introns: generation of stable insertions without selection.

Despite their commercial importance, there are relatively few facile methods for genomic manipulation of the lactic acid bacteria. Here, the lactococcal group II intron, Ll.ltrB, was targeted to insert efficiently into genes encoding malate decarboxylase (mleS) and tetracycline resistance (tetM) within the Lactococcus lactis genome. Integrants were readily identified and maintained in the absence of a selectable marker. Since splicing of the Ll.ltrB intron depends on the intron-encoded protein, targeted invasion with an intron lacking the intron open reading frame disrupted TetM and MleS function, and MleS activity could be partially restored by expressing the intron-encoded protein in trans. Restoration of splicing from intron variants lacking the intron-encoded protein illustrates how targeted group II introns could be used for conditional expression of any gene. Furthermore, the modified Ll.ltrB intron was used to separately deliver a phage resistance gene (abiD) and a tetracycline resistance marker (tetM) into mleS, without the need for selection to drive the integration or to maintain the integrant. Our findings demonstrate the utility of targeted group II introns as a potential food-grade mechanism for delivery of industrially important traits into the genomes of lactococci.

Bacterial Proteins↗
PubMed2006

Economic impact of transgenic crops in developing countries.

Transgenic crops are being adopted rapidly at the global level, but only a few developing countries are growing them in significant quantities. Why are these crops so successful in some countries but not in others? Farm level profitability ultimately determines whether farmers adopt and retain a new technology, but this depends on much more than technical performance. Recent economic studies in developing countries find positive, but highly variable, economic returns to adopting transgenic crops. These studies confirm that institutional factors such as national agricultural research capacity, environmental and food safety regulations, intellectual property rights and agricultural input markets matter at least as much as the technology itself in determining the level and distribution of economic benefits.

Crops, Agricultural↗
PubMed2000

Production of very-high-amylose potato starch by inhibition of SBE A and B.

High-amylose starch is in great demand by the starch industry for its unique functional properties. However, very few high-amylose crop varieties are commercially available. In this paper we describe the generation of very-high-amylose potato starch by genetic modification. We achieved this by simultaneously inhibiting two isoforms of starch branching enzyme to below 1% of the wild-type activities. Starch granule morphology and composition were noticeably altered. Normal, high-molecular-weight amylopectin was absent, whereas the amylose content was increased to levels comparable to the highest commercially available maize starches. In addition, the phosphorus content of the starch was increased more than fivefold. This unique starch, with its high amylose, low amylopectin, and high phosphorus levels, offers novel properties for food and industrial applications.

1,4-alpha-Glucan Branching Enzyme↗
PubMed1997

Natural behavior polymorphism due to a cGMP-dependent protein kinase of Drosophila.

Naturally occuring polymorphisms in behavior are difficult to map genetically and thus are refractory to molecular characterization. An exception is the foraging gene (for), a gene that has two naturally occurring variants in Drosophila melanogaster food-search behavior: rover and sitter. Molecular mapping placed for mutations in the dg2 gene, which encodes a cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG). Rovers had higher PKG activity than sitters, and transgenic sitters expressing a dg2 complementary DNA from rover showed transformation of behavior to rover. Thus, PKG levels affected food-search behavior, and natural variation in PKG activity accounted for a behavioral polymorphism.

Animals↗
PubMed2005

Animal cloning: problems and prospects.

An efficient animal cloning technology would provide many new opportunities for livestock agriculture, human medicine, and animal conservation. Nuclear cloning involves the production of animals that are genetically identical to the donor cells used in a technique known as nuclear transfer (NT). However, at present it is an inefficient process: in cattle, only around 6% of the embryos transferred to the reproductive tracts of recipient cows result in healthy, longterm surviving clones. Of concern are the high losses throughout gestation, during birth and in the post-natal period through to adulthood. Many of the pregnancy losses relate to failure of the placenta to develop and function correctly. Placental dysfunction may also have an adverse influence on postnatal health. These anomalies are probably due to incorrect epigenetic reprogramming of the donor genome following NT, leading to inappropriate patterns of gene expression during the development of clones. Whilst some physiological tests on surviving clones suggest normality, other reports indicate a variety of post-natal clone-associated abnormalities. This variability in outcome may reflect species-specific and/or cloning methodological differences. Importantly, to date it appears that these clone-associated phenotypes are not transmitted to offspring following sexual reproduction. This indicates that they represent epigenetic errors, rather than genetic errors, which are corrected during gametogenesis. Whilst this needs confirmation at the molecular level, it provides initial confidence in the first application of NT in agriculture, namely, the production of small numbers of cloned sires from genetically elite bulls, for natural mating, to effectively disseminate genetic gain. In addition to the animal welfare concerns with the technology, the underlying health of the animals and the consequential effect on food safety are critical aspects that require investigation to gain regulatory and consumer acceptance. Future improvements in animal cloning will largely arise from a greater understanding of the molecular mechanisms of reprogramming.

Animal Welfare↗
PubMed2006

Assessing the potential for unintended effects in genetically modified potatoes perturbed in metabolic and developmental processes. Targeted analysis of key nutrients and anti-nutrients.

Targeted compositional analysis was carried out on transgenic potato tubers of either cultivar (cv.) Record or cv. Desirée to assess the potential for unintended effects caused by the genetic modification process. The range of transgenic lines analysed included those modified in primary carbohydrate metabolism, polyamine biosynthesis and glycoprotein processing. Controls included wildtype tubers, tubers produced from plants regenerated through tissue culture (including a callus phase) and tubers derived from transformation with the 'empty vector' i.e. no specific target gene included (with the exception of the kanamycin resistance gene as a selectable marker). Metabolite analysis included soluble carbohydrates, glycoalkaloids, vitamin C, total nitrogen and fatty acids. Trypsin inhibitor activity was also assayed. These cover the major compounds recommended by the OECD in their Consensus Document on Compositional Considerations for New Varieties of Potatoes: Key Food and Feed Nutrients, Anti-Nutrients and Toxicants (2002). Data was statistically analysed using analysis of variance (ANOVA) for individual compounds and, where applicable, principal component analysis (PCA). In general, targeted compositional analysis revealed no consistent differences between GM lines and respective controls. No construct specifically induced unintended effects. Statistically significant differences between wildtype controls and specific GM lines did occur but appeared to be random and not associated with any specific construct. Indeed such significant differences were also found between wildtypes and both tissue culture derived tubers and tubers derived from transformation with the empty vector. This raises the possibility that somaclonal variation (known to occur significantly in potato, depending on genotype) may be responsible for an unknown proportion of any differences observed between specific GM lines and the wildtype. The most obvious differences seen in GC-MS profiles were between the two potato varieties used in the study.

Alkaloids↗