A proteomic-based approach to study underlying molecular responses of the small intestine of Wistar rats to genetically modified corn (MON810)

Morten Poulsen,Safaa Qusti,Angharad M R Gatehouse,Andrew Cockburn,Asmaa Al-Harbi,Martin G Edwards,Sahira Lary

doi:10.1007/s11248-019-00157-y

Abstract

A genetically modified (GM) commercial corn variety, MON810, resistant to European corn borer, has been shown to be non-toxic to mammals in a number of rodent feeding studies carried out in accordance with OECD Guidelines. Insect resistance results from expression of the Cry1Ab gene encoding an insecticidal Bt protein that causes lysis and cell death in susceptible insect larvae by binding to midgut epithelial cells, which is a key determinant of Cry toxin species specificity. Whilst whole animal studies are still recognised as the ‘gold standard’ for safety assessment, they only provide indirect evidence for changes at the cellular/organ/tissue level. In contrast, omics-based technologies enable mechanistic understanding of toxicological or nutritional events at the cellular/receptor level. To address this important knowledge-gap and to gain insights into the underlying molecular responses in rat to MON810, differential gene expression in the epithelial cells of the small intestine of rats fed formulated diets containing MON810, its near isogenic line, two conventional corn varieties, and a commercial (Purina™) corn-based control diet were investigated using comparative proteomic profiling. Pairwise and five-way comparisons showed that the majority of proteins that were differentially expressed in the small intestine epithelial cells in response to consumption of the different diets in both 7-day and 28-day studies were related to lipid and carbohydrate metabolism and protein biosynthesis. Irrespective of the diet, a limited number of stress-related proteins were shown to be differentially expressed. However these stress-related proteins differed between diets. No adverse clinical or behavioural effects, or biomarkers of adverse health, were observed in rats fed GM corn compared to the other corn diets. These findings suggest that MON810 has negligible effects on the small intestine of rats at the cellular level compared with the well-documented toxicity observed in susceptible insects.

Highlights

Since their commercialization in the mid 1990s, there has been global interest surrounding the use of Biotech crops (Genetically Modified (GM), transgenic crops) and their contribution to sustainable food production (James 2015)
Competing models differ in post-binding events that eventually kill insects, the currently accepted paradigm asserts that protoxins must be proteolytically cleaved to form a truncated active toxin, which binds to the high affinity receptor cadherin
There were small differences between the different treatment groups, these were not significant (Fig. 1a; Table S3; p = 0.859) and were within the normal limits for rats of this strain, age and sex. Those fed the commercial Purina chow gained more weight and those fed Reference diet 1 gained the least weight, whilst rats fed the parental near isogenic line (Control group) gained more weight compared to those fed MON810 (Test group), but these differences were small and non-significant

Summary

Introduction

Since their commercialization in the mid 1990s, there has been global interest surrounding the use of Biotech crops (Genetically Modified (GM), transgenic crops) and their contribution to sustainable food production (James 2015) Assurance of their safety for human and animal consumption is key to their acceptability and there remains widespread and vocal demand for additional evidence of their safety (Haslberger 2006; Hug 2008). Despite the large body of evidence pointing to the absence of histopathological abnormalities in tissues of animals fed GM-based corn diets, or clinical effects (Hammond et al 2006; MacKenzie et al 2007; Bartholomaeus et al 2013; Domingo 2016) there remains considerable concern by stakeholder groups, including risk assessment bodies, as to the safety of such products (Antoniou and Robinson 2017). What is surprising is the lack of evidence of any studies to investigate the potential effects of Bt present in cornbased diets at the subcellular or molecular level, and in particular, in comparable target tissues in mammals to those present in susceptible insects where the Cry proteins are known to bind (Pigott and Ellar 2007)

Methods

Results

Conclusion