Transcriptome analysis of liver and kidneys of rats chronically fed a NK603 Roundup-tolerant genetically modified maize
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE73888 | GEO | 2016/10/01
SECONDARY ACCESSION(S): PRJNA298337
REPOSITORIES: GEO
Similar Datasets
Project description:BACKGROUND:A previous 2-year rat feeding trial assessing potential toxicity of NK603 Roundup-tolerant genetically modified maize revealed blood and urine biochemical changes indicative of liver and kidney pathology. In an effort to obtain deeper insight into these findings, molecular profiling of the liver and kidneys from the same animals was undertaken. RESULTS:Transcriptomics showed no segregation of NK603 maize and control feed groups with false discovery rates ranging from 43 to 83% at a cut-off p value of 1%. Changes in gene expression were not reflective of liver and kidney toxic effects. Metabolomics identified 692 and 673 metabolites in kidney and liver, respectively. None of the statistically significant disturbances detected (12-56 for different test groups) survived a false discovery rate analysis. Differences in these metabolites between individual animals within a group were greater than the effect of test diets, which prevents a definitive conclusion on either pathology or safety. CONCLUSIONS:Even if the biological relevance of the statistical differences presented in this study is unclear, our results are made available for scrutiny by the scientific community and for comparison in future studies investigating potential toxicological properties of the NK603 corn.
| S-EPMC5306156 | biostudies-literature
Project description:There is an ongoing debate on the potential toxicity of genetically modified food. The ability of rodent feeding trials to assess the potential toxicity of these products is highly debated since a 2-year study in rats fed NK603 Roundup-tolerant genetically modified maize, treated or not with Roundup during the cultivation, resulted in anatomorphological and blood/urine biochemical changes indicative of liver and kidney structure and functional pathology. We used microarrays to detail the alterations in gene expression profiles associated with the consumption of a Roundup-tolerant genetically modified maize (NK603) sprayed or unsprayed with a Roundup herbicide from these same animals.
2016-10-01 | GSE73886 | GEO
Project description:There is an ongoing debate on the potential toxicity of genetically modified food. The ability of rodent feeding trials to assess the potential toxicity of these products is highly debated since a 2-year study in rats fed NK603 Roundup-tolerant genetically modified maize, treated or not with Roundup during the cultivation, resulted in anatomorphological and blood/urine biochemical changes indicative of liver and kidney structure and functional pathology. We used microarrays to detail the alterations in gene expression profiles associated with the consumption of a Roundup-tolerant genetically modified maize (NK603) sprayed or unsprayed with a Roundup herbicide from these same animals.
2016-10-01 | GSE73884 | GEO
Project description:Transcriptome analysis of liver and kidneys of rats chronically fed a NK603 Roundup-tolerant genetically modified maize
| PRJNA298337 | ENA
Project description:AIM:To examine the effects of ethanol-induced proteasome inhibition, and the effects of proteasome inhibition in the regulation of epigenetic mechanisms. METHODS:Rats were fed ethanol for 1 mo using the Tsukamoto-French model and were compared to rats given the proteasome inhibitor PS-341 (Bortezomib, Velcade(TM)) by intraperitoneal injection. Microarray analysis and real time PCR were performed and proteasome activity assays and Western blot analysis were performed using isolated nuclei. RESULTS:Chronic ethanol feeding caused a significant inhibition of the ubiquitin proteasome pathway in the nucleus, which led to changes in the turnover of transcriptional factors, histone-modifying enzymes, and, therefore, affected epigenetic mechanisms. Chronic ethanol feeding was related to an increase in histone acetylation, and it is hypothesized that the proteasome proteolytic activity regulated histone modifications by controlling the stability of histone modifying enzymes, and, therefore, regulated the chromatin structure, allowing easy access to chromatin by RNA polymerase, and, thus, proper gene expression. Proteasome inhibition by PS-341 increased histone acetylation similar to chronic ethanol feeding. In addition, proteasome inhibition caused dramatic changes in hepatic remethylation reactions as there was a significant decrease in the enzymes responsible for the regeneration of S-adenosylmethionine, and, in particular, a significant decrease in the betaine-homocysteine methyltransferase enzyme. This suggested that hypomethylation was associated with proteasome inhibition, as indicated by the decrease in histone methylation. CONCLUSION:The role of proteasome inhibition in regulating epigenetic mechanisms, and its link to liver injury in alcoholic liver disease, is thus a promising approach to study liver injury due to chronic ethanol consumption.
| S-EPMC2653439 | biostudies-literature
Project description:This study was conducted to follow up on apparent differences in growth, relative organ sizes, cellular stress and immune function in Atlantic salmon fed genetically modified (GM) Bt-maize compared to the non-modified parental maize line. Gene expression profiling on the distal intestinal segment and liver were performed by the cGRASP 16K salmonid cDNA microarray. Analysis of the intestinal microarray data revealed nearly 500 differentially regulated genes with a false discovery rate of zero, despite modest fold differences (average 2.4 for the down-regulated and 1.7 for the up-regulated genes). However, nine out of ten genes were found not to be significantly different when followed up by quantitative polymerase chain reaction (qPCR), but direction and magnitude of the change was generally confirmed, at least for the up-regulated genes. For the liver microarray data, statistical analyses could not be performed due to constraints in the design. qPCR revealed some differentially regulated genes in the liver, including up-regulation of gelsolin precursor, down-regulation of ferritin heavy subunit and a tendency towards down-regulation of metallothionein B. This, combined with up-regulation of anti-apoptotic protein NR13 and a tendency towards up-regulation of both ferritin heavy chain and metallothionein A and B in the distal intestine, suggests changes in cellular stress/ anti-oxidant status. This corresponds well with, and strengthens previous findings in these fish. To exclude possible confounding factors, the maize ingredients were analyzed for mycotoxins and metabolites, and the GM maize variety contain 90M-NM-<g/kg deoxynivalenol (DON), compared to levels below the detection limit in the non-GM maize. Numerous differences were also seen in the metabolite profiles of the two maize varieties, some of which seem to be connected to the mycotoxin level. The effects on salmon observed in the current and in previous studies correspond relatively well with effects of DON as reported in the literature for other production animals, but knowledge regarding effects and harmful dose levels in fish are practically non-existing, thus it is difficult to conclude whether the observed effects in the fish are caused by the DON level or by some other aspect of the GM maize ingredient.
2010-10-01 | E-TABM-1056 | biostudies-arrayexpress
Project description:DP915635 maize was genetically modified (GM) to express the IPD079Ea protein for corn rootworm (Diabrotica spp.) control. DP915635 maize also expresses the phosphinothricin acetyltransferase (PAT) protein for tolerance to glufosinate herbicide and the phosphomannose isomerase (PMI) protein that was used as a selectable marker. A field study was conducted at ten sites in the United States and Canada during the 2019 growing season. Of the 11 agronomic endpoints that were evaluated, two of them (early stand count and days to flowering) were statistically significant compared with the control maize based on unadjusted p-values; however, these differences were not significant after FDR-adjustment of p-values. Composition analytes from DP915635 maize grain and forage (proximates, fiber, minerals, amino acids, fatty acids, vitamins, anti-nutrients, and secondary metabolites) were compared to non-GM near-isoline control maize (control maize) and non-GM commercial maize (reference maize). Statistically significant differences were observed for 7 of the 79 compositional analytes (16:1 palmitoleic acid, 18:0 stearic acid, 18:1 oleic acid, 18:2 linoleic acid, 24:0 lignoceric acid, methionine, and α-tocopherol); however, these differences were not significant after FDR-adjustment. Additionally, all of the values for composition analytes fell within the range of natural variation established from the in-study reference range, literature range, and/or tolerance interval. These results demonstrate that DP915635 is agronomically and compositionally comparable to non-GM maize represented by non-GM near-isoline control maize and non-GM commercial maize.
| S-EPMC10161957 | biostudies-literature
Project description:The genetically modified maize event MON810 expresses a Bacillus thuringiensis-derived gene, which encodes the insecticidal protein Cry1Ab to control some lepidopteran insect pests such as the European corn borer. It has been claimed that the immune system may be affected following the oral/intragastric administration of the MON810 maize in various different animal species. In the frame of the EU-funded project GRACE, two 90-day feeding trials, the so-called studies D and E, were performed to analyze the humoral and cellular immune responses of male and female Wistar Han RCC rats fed the MON810 maize. A MON810 maize variety of Monsanto was used in the study D and a MON810 maize variety of Pioneer Hi-Bred was used in the study E. The total as well as the maize protein- and Cry1Ab-serum-specific IgG, IgM, IgA and IgE levels, the proliferative activity of the lymphocytes, the phagocytic activity of the granulocytes and monocytes, the respiratory burst of the phagocytes, a phenotypic analysis of spleen, thymus and lymph node cells as well as the in vitro production of cytokines by spleen cells were analyzed. No specific Cry1Ab immune response was observed in MON810 rats, and anti-maize protein antibody responses were similar in MON810 and control rats. Single parameters were sporadically altered in rats fed the MON810 maize when compared to control rats, but these alterations are considered to be of no immunotoxicological significance.
| S-EPMC6015625 | biostudies-literature
Project description:Folates are indispensable co-factors for one-carbon metabolism in all organisms. In humans, suboptimal folate intake results in serious disorders. One promising strategy for improving human folate status is to enhance folate levels in food crops by metabolic engineering. In this study, we cloned two GmGCHI (GTP cyclohydrolase I) genes (Gm8gGCHI and Gm3gGCHI) and one GmADCS (aminodeoxychorismate synthase) gene from soybean, which are responsible for synthesizing the folate precursors pterin and p-aminobenzoate, respectively. We initially confirmed their functions in transgenic Arabidopsis plants and found that Gm8gGCHI increased pterin and folate production more than Gm3gGCHI did. We then co-expressed Gm8gGCHI and GmADCS driven by endosperm-specific promoters in maize and wheat, two major staple crops, to boost their folate metabolic flux. A 4.2-fold and 2.3-fold increase in folate levels were observed in transgenic maize and wheat grains, respectively. To optimize wheat folate enhancement, codon-optimized Gm8gGCHI and tomato LeADCS genes under the control of a wheat endosperm-specific glutenin promoter (1Dx5) were co-transformed. This yielded a 5.6-fold increase in folate in transgenic wheat grains (Gm8gGCHI+/LeADCS+). This two-gene co-expression strategy therefore has the potential to greatly enhance folate levels in maize and wheat, thus improving their nutritional value.
| S-EPMC6411382 | biostudies-literature
Project description:The Cauliflower Mosaic Virus 35S promoter sequence, CaMV P-35S, is one of several commonly used genetic targets to detect genetically modified maize and is found in most GMOs. In this research we report the finding of an alternative P-35S sequence and its incidence in GM maize marketed in Jordan. The primer pair normally used to amplify a 123 bp DNA fragment of the CaMV P-35S promoter in GMOs also amplified a previously undetected alternative sequence of CaMV P-35S in GM maize samples which we term V3. The amplified V3 sequence comprises 386 base pairs and was not found in the standard wild-type maize, MON810 and MON 863 GM maize. The identified GM maize samples carrying the V3 sequence were found free of CaMV when compared with CaMV infected brown mustard sample. The data of sequence alignment analysis of the V3 genetic element showed 90% similarity with the matching P-35S sequence of the cauliflower mosaic virus isolate CabbB-JI and 99% similarity with matching P-35S sequences found in several binary plant vectors, of which the binary vector locus JQ693018 is one example. The current study showed an increase of 44% in the incidence of the identified 386 bp sequence in GM maize sold in Jordan's markets during the period 2009 and 2012.
| S-EPMC5033183 | biostudies-literature