The in vivo genotoxicity studies on nivalenol and deoxynivalenolReport as inadecuate

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1 Anses Laboratoire de Fougères 2 Institut Pasteur de Lille

Abstract : Nivalenol NIV and deoxynivalenol DON are structurally related mycotoxins produced by Fusarium fungi. These fungi typically infest cereal crops such as wheat, maize, barley, oats and rye, and NIV and DON are regularly found in cereal grains, food and feed. Recent risk assessments identified possible data gaps for both DON and NIV in particular with respect to genotoxicity and carcinogenicity. The overall objective of the project was to assess the genotoxicity of DON and NIV, including the identification of potential modes of action. A battery of in vivo genotoxicity tests was performed in mice: Comet assay with and without fpg in seven organs duodenum, colon, blood, liver, spleen, kidney, bone marrow, micronucleus assay in bone marrow and colon, and Pig-a assay in peripheral blood. In addition, to clarify the genotoxic mode of action of both mycotoxins, we performed in vitro Comet assay studies in TK6 cells to investigate potential genotoxic oxidative stress induced by mycotoxins. The response in all the genotoxicity assays with NIV after three oral doses at 5, 10 and 20 mg-kg, were uniformly negative. In the case of DON, we found that DON failed to induce micronuclei formation in bone marrow and colon and failed to induce DNA damage in all organs observed by the Comet assay with and without fpg at 4, 8 and 16 mg-kg. The Pig-a assay with DON after three oral gavage doses at 2, 4 and 8 mg-kg, did not show any mutagenic effect at day 28 and 45 after the last dose. In vitro studies indicated that both mycotoxins did not induce DNA damage in the Comet assay with or without fpg in TK6 cells even after GSH depletion. It was concluded that NIV and DON could be considered as devoid of genotoxic potential and pose no genotoxic or mutagenic risk.

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Keywords : in vivo and in vitro genotoxicity Comet assay micronucleus Pig-a deoxynivalenol nivalenol

Mots-clés : test in vitro comet génotoxicité test in vivo

Author: Ludovic Le Hégarat - Natsuko Takakura - S Simar - Fabrice Nesslany - Valérie Fessard -



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