title: An integrated multi-omics analysis of the NK603 Roundup-tolerant GM maize reveals metabolism disturbances caused by the transformation process.
abstract: Glyphosate tolerant genetically modified (GM) maize NK603 was assessed as 'substantially equivalent' to its isogenic counterpart by a nutrient composition analysis in order to be granted market approval. We have applied contemporary in depth molecular profiling methods of NK603 maize kernels (sprayed or unsprayed with Roundup) and the isogenic corn to reassess its substantial equivalence status. Proteome profiles of the maize kernels revealed alterations in the levels of enzymes of glycolysis and TCA cycle pathways, which were reflective of an imbalance in energy metabolism. Changes in proteins and metabolites of glutathione metabolism were indicative of increased oxidative stress. The most pronounced metabolome differences between NK603 and its isogenic counterpart consisted of an increase in polyamines including N-acetyl-cadaverine (2.9-fold), N-acetylputrescine (1.8-fold), putrescine (2.7-fold) and cadaverine (28-fold), which depending on context can be either protective or a cause of toxicity. Our molecular profiling results show that NK603 and its isogenic control are not substantially equivalent.
authors.affiliation: Gene Expression and Therapy Group, King's College London, Faculty of Life Sciences &Medicine, Department of Medical and Molecular Genetics, 8th Floor, Tower Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, United Kingdom.
authors.forename: Robin
authors.initials: R
authors.lastname: Mesnage
authors.affiliation: Genøk, Center for Biosafety, The Science Park, P.O. Box 6418 Tromsø 9294, Norway.
authors.forename: Sarah Z
authors.initials: SZ
authors.lastname: Agapito-Tenfen
authors.affiliation: CropScience Department, Federal University of Santa Catarina, Rod. Admar Gonzaga 1346, 88034-000 Florianópolis, Brazil.
authors.forename: Vinicius
authors.initials: V
authors.lastname: Vilperte
authors.affiliation: Proteomics Facility, King's College London, Institute of Psychiatry, London SE5 8AF, United Kingdom.
authors.forename: George
authors.initials: G
authors.lastname: Renney
authors.affiliation: Proteomics Facility, King's College London, Institute of Psychiatry, London SE5 8AF, United Kingdom.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Ward
authors.affiliation: University of Caen, Institute of Biology, EA 2608 and Network on Risks, Quality and Sustainable Environment, MRSH, Esplanade de la Paix, University of Caen, Caen 14032, Cedex, France.
authors.forename: Gilles-Eric
authors.initials: GE
authors.lastname: Séralini
authors.affiliation: CropScience Department, Federal University of Santa Catarina, Rod. Admar Gonzaga 1346, 88034-000 Florianópolis, Brazil.
authors.forename: Rubens O
authors.initials: RO
authors.lastname: Nodari
authors.affiliation: Gene Expression and Therapy Group, King's College London, Faculty of Life Sciences &Medicine, Department of Medical and Molecular Genetics, 8th Floor, Tower Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, United Kingdom.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Antoniou
mesh_terms: D002103:Cadaverine / Q000737:chemistry; D002853:Chromatography, Liquid; D002952:Citric Acid Cycle; D019295:Computational Biology; D017343:Genes, Plant; D005998:Glycine / Q000031:analogs & derivatives; D006019:Glycolysis; D053209:Herbicide Resistance / Q000235:genetics*; D006540:Herbicides / Q000737:chemistry*; D013058:Mass Spectrometry; D055442:Metabolome; D018384:Oxidative Stress; D030821:Plants, Genetically Modified / Q000235:genetics / Q000378:metabolism*; D011073:Polyamines / Q000737:chemistry; D020543:Proteome; D011700:Putrescine / Q000031:analogs & derivatives / Q000737:chemistry; D053719:Tandem Mass Spectrometry; D003313:Zea mays / Q000235:genetics / Q000378:metabolism*; D000097797:Glyphosate
chemical_list: D002103:Cadaverine; D005998:Glycine; D006540:Herbicides; D011073:Polyamines; D020543:Proteome; D011700:Putrescine; D000097797:Glyphosate; C026212:N-acetylputrescine