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

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

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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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.
Original languageEnglish
JournalTransgenic Research
Volume28
Issue number5-6
Pages (from-to)479–498
ISSN0962-8819
DOIs
Publication statusPublished - 2019

Keywords

  • Bacillus thuringiensis
  • Cry1Ab protein
  • Epithelial cells
  • Feeding trials
  • MON810
  • Proteome
  • Stress-proteins
  • Wistar rats

Cite this

Al-Harbi, Asmaa ; Lary, Sahira ; Edwards, Martin G ; Qusti, Safaa ; Cockburn, Andrew ; Poulsen, Morten ; Gatehouse, Angharad M R. / A proteomic-based approach to study underlying molecular responses of the small intestine of Wistar rats to genetically modified corn (MON810). In: Transgenic Research. 2019 ; Vol. 28, No. 5-6. pp. 479–498.
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title = "A proteomic-based approach to study underlying molecular responses of the small intestine of Wistar rats to genetically modified corn (MON810)",
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.",
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author = "Asmaa Al-Harbi and Sahira Lary and Edwards, {Martin G} and Safaa Qusti and Andrew Cockburn and Morten Poulsen and Gatehouse, {Angharad M R}",
year = "2019",
doi = "10.1007/s11248-019-00157-y",
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A proteomic-based approach to study underlying molecular responses of the small intestine of Wistar rats to genetically modified corn (MON810). / Al-Harbi, Asmaa; Lary, Sahira; Edwards, Martin G; Qusti, Safaa; Cockburn, Andrew; Poulsen, Morten; Gatehouse, Angharad M R.

In: Transgenic Research, Vol. 28, No. 5-6, 2019, p. 479–498.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - A proteomic-based approach to study underlying molecular responses of the small intestine of Wistar rats to genetically modified corn (MON810)

AU - Al-Harbi, Asmaa

AU - Lary, Sahira

AU - Edwards, Martin G

AU - Qusti, Safaa

AU - Cockburn, Andrew

AU - Poulsen, Morten

AU - Gatehouse, Angharad M R

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N2 - 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.

AB - 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.

KW - Bacillus thuringiensis

KW - Cry1Ab protein

KW - Epithelial cells

KW - Feeding trials

KW - MON810

KW - Proteome

KW - Stress-proteins

KW - Wistar rats

U2 - 10.1007/s11248-019-00157-y

DO - 10.1007/s11248-019-00157-y

M3 - Journal article

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VL - 28

SP - 479

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JO - Transgenic Research

JF - Transgenic Research

SN - 0962-8819

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ER -