Transcriptome and Metabolome Analysis of Liver and Kidneys of Rats Chronically Fed NK603 Roundup-tolerant Genetically Modified Maize

Overview

Journal Environ Sci Eur

Publisher Springer

Specialty Environmental Health

Date 2017 Feb 28

PMID 28239534

Citations 3

Authors

Robin Mesnage

Matthew Arno

Gilles-Eric Seralini

Michael N Antoniou

Affiliations

Soon will be listed here.

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 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.

Citing Articles

Dietary Behavior of Fed with Genetically-Modified Corn or Roundup.

Elias R, Talyn B, Melchiorre E J Xenobiot. 2021; 11(4):215-227.

PMID: 34940514 PMC: 8703958. DOI: 10.3390/jox11040014.

Roundup, but Not Roundup-Ready Corn, Increases Mortality of .

Talyn B, Lemon R, Badoella M, Melchiorre D, Villalobos M, Elias R Toxics. 2019; 7(3).

PMID: 31370250 PMC: 6789507. DOI: 10.3390/toxics7030038.

The GMO90+ Project: Absence of Evidence for Biologically Meaningful Effects of Genetically Modified Maize-based Diets on Wistar Rats After 6-Months Feeding Comparative Trial.

Coumoul X, Servien R, Juricek L, Kaddouch-Amar Y, Lippi Y, Berthelot L Toxicol Sci. 2018; 168(2):315-338.

PMID: 30535037 PMC: 6432862. DOI: 10.1093/toxsci/kfy298.

References

Wilson A, Latham J, Steinbrecher R . Transformation-induced mutations in transgenic plants: analysis and biosafety implications. Biotechnol Genet Eng Rev. 2012; 23:209-37. DOI: 10.1080/02648725.2006.10648085. View

Boudonck K, Mitchell M, Nemet L, Keresztes L, Nyska A, Shinar D . Discovery of metabolomics biomarkers for early detection of nephrotoxicity. Toxicol Pathol. 2009; 37(3):280-92. DOI: 10.1177/0192623309332992. View

Agapito-Tenfen S, Vilperte V, Benevenuto R, Rover C, Traavik T, Nodari R . Effect of stacking insecticidal cry and herbicide tolerance epsps transgenes on transgenic maize proteome. BMC Plant Biol. 2014; 14:346. PMC: 4273480. DOI: 10.1186/s12870-014-0346-8. View

Li X, Ding C, Wang X, Liu B . Comparison of the physiological characteristics of transgenic insect-resistant cotton and conventional lines. Sci Rep. 2015; 5:8739. PMC: 4348622. DOI: 10.1038/srep08739. View

Herrero M, Ibanez E, Martin-Alvarez P, Cifuentes A . Analysis of chiral amino acids in conventional and transgenic maize. Anal Chem. 2007; 79(13):5071-7. DOI: 10.1021/ac070454f. View

Manetti C, Bianchetti C, Casciani L, Castro C, Di Cocco M, Miccheli A . A metabonomic study of transgenic maize (Zea mays) seeds revealed variations in osmolytes and branched amino acids. J Exp Bot. 2006; 57(11):2613-25. DOI: 10.1093/jxb/erl025. View

Agapito-Tenfen S, Guerra M, Wikmark O, Nodari R . Comparative proteomic analysis of genetically modified maize grown under different agroecosystems conditions in Brazil. Proteome Sci. 2013; 11(1):46. PMC: 4176129. DOI: 10.1186/1477-5956-11-46. View

Dehaven C, Evans A, Dai H, Lawton K . Organization of GC/MS and LC/MS metabolomics data into chemical libraries. J Cheminform. 2010; 2(1):9. PMC: 2984397. DOI: 10.1186/1758-2946-2-9. View

Bohn T, Cuhra M, Traavik T, Sanden M, Fagan J, Primicerio R . Compositional differences in soybeans on the market: glyphosate accumulates in Roundup Ready GM soybeans. Food Chem. 2014; 153:207-15. DOI: 10.1016/j.foodchem.2013.12.054. View

10.

Guyton K, Loomis D, Grosse Y, El Ghissassi F, Benbrahim-Tallaa L, Guha N . Carcinogenicity of tetrachlorvinphos, parathion, malathion, diazinon, and glyphosate. Lancet Oncol. 2015; 16(5):490-1. DOI: 10.1016/S1470-2045(15)70134-8. View

11.

Fonseca C, Planchon S, Serra T, Chander S, Saibo N, Renaut J . In vitro culture may be the major contributing factor for transgenic versus nontransgenic proteomic plant differences. Proteomics. 2014; 15(1):124-34. DOI: 10.1002/pmic.201400018. View

12.

Shepherd L, Hackett C, Alexander C, McNicol J, Sungurtas J, Stewart D . Modifying glycoalkaloid content in transgenic potato--Metabolome impacts. Food Chem. 2015; 187:437-43. DOI: 10.1016/j.foodchem.2015.04.111. View

13.

Ogiso S, Matsumoto T, Nimura Y . The role of polyamines in liver regeneration after hepatectomy with ischemic injury. Surg Today. 1997; 27(9):833-9. DOI: 10.1007/BF02385274. View

14.

Mesnage R, Agapito-Tenfen S, Vilperte V, Renney G, Ward M, Seralini G . An integrated multi-omics analysis of the NK603 Roundup-tolerant GM maize reveals metabolism disturbances caused by the transformation process. Sci Rep. 2016; 6:37855. PMC: 5171704. DOI: 10.1038/srep37855. View

15.

Mesnage R, Defarge N, Spiroux de Vendomois J, Seralini G . Potential toxic effects of glyphosate and its commercial formulations below regulatory limits. Food Chem Toxicol. 2015; 84:133-53. DOI: 10.1016/j.fct.2015.08.012. View

16.

Mesnage R, Renney G, Seralini G, Ward M, Antoniou M . Multiomics reveal non-alcoholic fatty liver disease in rats following chronic exposure to an ultra-low dose of Roundup herbicide. Sci Rep. 2017; 7:39328. PMC: 5220358. DOI: 10.1038/srep39328. View

17.

Nicolia A, Manzo A, Veronesi F, Rosellini D . An overview of the last 10 years of genetically engineered crop safety research. Crit Rev Biotechnol. 2013; 34(1):77-88. DOI: 10.3109/07388551.2013.823595. View

18.

Zolla L, Rinalducci S, Antonioli P, Righetti P . Proteomics as a complementary tool for identifying unintended side effects occurring in transgenic maize seeds as a result of genetic modifications. J Proteome Res. 2008; 7(5):1850-61. DOI: 10.1021/pr0705082. View

19.

Spiroux de Vendomois J, Roullier F, Cellier D, Seralini G . A comparison of the effects of three GM corn varieties on mammalian health. Int J Biol Sci. 2009; 5(7):706-26. PMC: 2793308. DOI: 10.7150/ijbs.5.706. View

20.

Ohta T, Masutomi N, Tsutsui N, Sakairi T, Mitchell M, Milburn M . Untargeted metabolomic profiling as an evaluative tool of fenofibrate-induced toxicology in Fischer 344 male rats. Toxicol Pathol. 2009; 37(4):521-35. DOI: 10.1177/0192623309336152. View