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Transcriptome and metabolome analysis of liver and kidneys of rats chronically fed NK603 Roundup-tolerant genetically modified maize.

ABSTRACT: 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.

SUBMITTER: Mesnage R

PROVIDER: S-EPMC5306156 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Transcriptome and metabolome analysis of liver and kidneys of rats chronically fed NK603 Roundup-tolerant genetically modified maize.

Mesnage Robin R Arno Matthew M Séralini Gilles-Eric GE Antoniou Michael N MN

Environmental sciences Europe 20170207 1

<h4>Background</h4>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.<h4>Results</h4>Transcriptomics showed no segregation of NK603 maize and control feed groups with false discovery rates ranging from 43 ...[more]

PMID: 28239534

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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.

Dataset Information

Transcriptome and metabolome analysis of liver and kidneys of rats chronically fed NK603 Roundup-tolerant genetically modified maize.

Publications

Transcriptome and metabolome analysis of liver and kidneys of rats chronically fed NK603 Roundup-tolerant genetically modified maize.

Similar Datasets

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