Effects of chronic deoxynivalenol exposure on p53 heterozygous and p53 homozygous mice

Bondy, Genevieve S.; Coady, Laurie; Curran, Ivan; Caldwell, Douglas R.; Armstrong, Cheryl; Aziz, Shuokr Qarani; Nunnikhoven, A.; Gannon, Anne Marie; Liston, Virginia; Shenton, Jacintha; Mehta, Rekha

doi:10.1016/j.fct.2016.07.018

Cited by 12 publications

(18 citation statements)

References 57 publications

(59 reference statements)

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“…Several long-term studies showed that DON is not a carcinogenic compound (29, 30); consequently, this mycotoxin has been classified in group 3 (“not classifiable as to its carcinogenicity to humans”) by the World Health Organization (WHO) International Agency for Research on Cancer (IARC). In the present study, DON, used at realistic levels (31, 32), did not induce detectable DNA damage in the intestine.…”

Section: Discussionmentioning

confidence: 99%

The Food Contaminant Deoxynivalenol Exacerbates the Genotoxicity of Gut Microbiota

Payros

Dobrindt

Martín

et al. 2017

mBio

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An increasing number of human beings from developed countries are colonized by Escherichia coli strains producing colibactin, a genotoxin suspected to be associated with the development of colorectal cancers. Deoxynivalenol (DON) is the most prevalent mycotoxin that contaminates staple food—especially cereal products—in Europe and North America. This study investigates the effect of the food contaminant DON on the genotoxicity of the E. coli strains producing colibactin. In vitro, intestinal epithelial cells were coexposed to DON and E. coli producing colibactin. In vivo, newborn rats colonized at birth with E. coli producing colibactin were fed a DON-contaminated diet. Intestinal DNA damage was estimated by the phosphorylation of histone H2AX. DON exacerbates the genotoxicity of the E. coli producing colibactin in a time- and dose-dependent manner in vitro. Although DON had no effect on the composition of the gut microbiota, and especially on the number of E. coli, a significant increase in DNA damage was observed in intestinal epithelial cells of animals colonized by E. coli strains producing colibactin and coexposed to DON compared to animals colonized with E. coli strains unable to produce colibactin or animals exposed only to DON. In conclusion, our data demonstrate that the genotoxicity of E. coli strains producing colibactin, increasingly present in the microbiota of asymptomatic human beings, is modulated by the presence of DON in the diet. This raises questions about the synergism between food contaminants and gut microbiota with regard to intestinal carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

The Food Contaminant Deoxynivalenol Exacerbates the Genotoxicity of Gut Microbiota

Payros

Dobrindt

Martín

et al. 2017

mBio

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“…In 2016, Bondy et al. () performed a study on p53+/+ and p53+/− male mice exposed to DON (10 animals per group) via diet during 26 weeks at doses of 0, 1, 5 and 10 mg/kg diet equal to 0, 0.09, 0.53 and 1.57 mg/kg bw per day as calculated by the authors. No toxicologically significant modifications of haematological and biochemical parameters were observed.…”

Section: Hazard Identification and Characterisationmentioning

confidence: 99%

“…In a subsequent subchronic study, the effects of DON were studied in p53 heterozygous (p53+/−) and p53 homozygous (p53+/+) male mice (Bondy et al., ) (see also Section 7.2.4). Groups of animals (n = 10) received a diet containing 0, 1, 5 or 10 mg DON/kg diet for 26 weeks.…”

Section: Hazard Identification and Characterisationmentioning

confidence: 99%

“…In addition, the CONTAM Panel analysed the dose–response data from the recently published subchronic study of Bondy et al. () on p53+/+ and p53+/− mice (see Section 7.2.3) using the doses of 0, 0.09, 0.53 and 1.57 mg/kg bw per day as calculated by the authors from the same concentrations of DON in the diet (0, 1, 5 and 10 mg DON/kg feed) as used by Iverson et al. ().…”

Section: Hazard Identification and Characterisationmentioning

confidence: 99%

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Risks to human and animal health related to the presence of deoxynivalenol and its acetylated and modified forms in food and feed

Knutsen¹,

Alexander²,

Barregård³

et al. 2017

EFS2

192

187

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Deoxynivalenol (DON) is a mycotoxin primarily produced by Fusarium fungi, occurring predominantly in cereal grains. Following the request of the European Commission, the CONTAM Panel assessed the risk to animal and human health related to DON, 3-acetyl-DON (3-Ac-DON), 15-acetyl-DON (15-Ac-DON) and DON-3-glucoside in food and feed. A total of 27,537, 13,892, 7,270 and 2,266 analytical data for DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside, respectively, in food, feed and unprocessed grains collected from 2007 to 2014 were used. For human exposure, grains and grain-based products were main sources, whereas in farm and companion animals, cereal grains, cereal by-products and forage maize contributed most. DON is rapidly absorbed, distributed, and excreted. Since 3-Ac-DON and 15-Ac-DON are largely deacetylated and DON-3-glucoside cleaved in the intestines the same toxic effects as DON can be expected. The TDI of 1 lg/kg bw per day, that was established for DON based on reduced body weight gain in mice, was therefore used as a group-TDI for the sum of DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside. In order to assess acute human health risk, epidemiological data from mycotoxicoses were assessed and a group-ARfD of 8 lg/kg bw per eating occasion was calculated. Estimates of acute dietary exposures were below this dose and did not raise a health concern in humans. The estimated mean chronic dietary exposure was above the group-TDI in infants, toddlers and other children, and at high exposure also in adolescents and adults, indicating a potential health concern. Based on estimated mean dietary concentrations in ruminants, poultry, rabbits, dogs and cats, most farmed fish species and horses, adverse effects are not expected. At the high dietary concentrations, there is a potential risk for chronic adverse effects in pigs and fish and for acute adverse effects in cats and farmed mink.This is an open access article under the terms of the Creative Commons Attribution-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited and no modifications or adaptations are made.The EFSA Journal is a publication of the European Food Safety Authority, an agency of the European Union. Deoxynivalenol and its acetylated and modified forms in food and feed www.efsa.europa.eu/efsajournal 2 EFSA Journal 2017;15(9):4718 Deoxynivalenol and its acetylated and modified forms in food and feed www.efsa.europa.eu/efsajournal 3 EFSA Journal 2017;15(9):4718 Deoxynivalenol and its acetylated and modified forms in food and feed www.efsa.europa.eu/efsajournal 4 EFSA Journal 2017;15(9):471870% of ingested DON is excreted via urine, of which about 80% was in conjugated forms, mainly as DON-15-glucuronide that was about threefold more efficiently formed than DON-3-glucuronide. After a single oral exposure to DON, feed refusal appeared very quickly in mice. Previous risk assessments of DON conducted by the Scientific Committee on Food (SCF) in 1999 and by the Joint FAO/WHO Expert Committee on Food Additives...

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“…Deoxynivalenol (DON, 1 ; Figure a) is a trichothecene mycotoxin produced by various Fusarium species, including Fusarium graminearum and Fusarium culmorum . These species mainly colonize wheat, barley, corn, and oats in temperate regions of Europe . Infection of the crop by Fusarium fungi is favored during a prolonged cool, moist growing and harvest season .…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Isotope‐Labeled Deoxynivalenol‐15‐O‐Glycosides

et al. 2017

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A versatile and efficient protocol for the Schmidt glycosylation of 3‐acetyldeoxynivalenol (3‐ADON) and subsequent deprotection has been developed to gain access to deoxynivalenol‐15‐O‐glycosides in reasonable amounts for biological analysis and further investigations. By using this protocol with [13C6]glycosyl donors, we were able to prepare isotope‐labeled deoxynivalenol‐15‐O‐glycosides, which are pivotal to enabling accurate quantification of masked mycotoxins by LC–MS.

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Effects of chronic deoxynivalenol exposure on p53 heterozygous and p53 homozygous mice

Cited by 12 publications

References 57 publications

The Food Contaminant Deoxynivalenol Exacerbates the Genotoxicity of Gut Microbiota

The Food Contaminant Deoxynivalenol Exacerbates the Genotoxicity of Gut Microbiota

Risks to human and animal health related to the presence of deoxynivalenol and its acetylated and modified forms in food and feed

Synthesis of Isotope‐Labeled Deoxynivalenol‐15‐O‐Glycosides

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