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Toxicology of 3-epi-deoxynivalenol,a deoxynivalenol-transformation product by Devosia mutans 17-2-E-8
Institution:1. Guelph Food Research Centre, Agriculture and Agri-Food Canada, Guelph, Ontario, Canada;2. School of Environmental Sciences, University of Guelph, Guelph, Ontario, Canada;3. Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada;1. College of Veterinary Medicine, Sichuan Agricultural University, Ya’an 625014, China;2. Sichuan Province Key Laboratory of Animal Disease & Human Health, Ya’an 625014, China;3. Key Laboratory of Environmental Hazard and Human Health of Sichuan Province, Ya’an 625014, China;4. School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang 621010, China;1. College of Food Science and Engineering, Wuhan Polytechnic University, China;2. Key Laboratory for Deep Processing of Major Grain and Oil, China;3. Wuhan Polytechnic University, 68 Xuefu South Road, Changqing Garden, Wuhan 430023, Hubei, China;1. State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Synergetic Innovation Center of Food Safety and Nutrition, Jiangnan University, Wuxi, Jiangsu 214122, China;2. Institute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agricultural Science, Beijing 100081, China;3. Department of Food Science, Shaanxi University of Science Technology, Xian 710021, China;4. Department of Environmental Health Science, The University of Georgia, Athens, GA 30602, United States
Abstract:Microbial detoxification of deoxynivalenol (DON) represents a new approach to treating DON-contaminated grains. A bacterium Devosia mutans 17-2-E-8 was capable of completely transforming DON into a major product 3-epi-DON and a minor product 3-keto-DON. Evaluation of toxicities of these DON-transformation products is an important part of hazard characterization prior to commercialization of the biotransformation application. Cytotoxicities of the products were demonstrated by two assays: a MTT bioassay assessing cell viability and a BrdU assay assessing DNA synthesis. Compared with DON, the IC50 values of 3-epi-DON and 3-keto-DON were respectively 357 and 3.03 times higher in the MTT bioassay, and were respectively 1181 and 4.54 times higher in the BrdU bioassay. Toxicological effects of 14-day oral exposure of the B6C3F1 mouse to DON and 3-epi-DON were also investigated. Overall, there were no differences between the control (free of toxin) and the 25 mg/kg bw/day or 100 mg/kg bw/day 3-epi-DON treatments in body and organ weights, hematology and organ histopathology. However, in mice exposed to DON (2 mg/kg bw/day), white blood cell numbers and serum immunoglobulin levels were altered relative to controls, and lesions were observed in adrenals, thymus, stomach, spleen and colon. Taken together, in vitro and in vivo studies indicate that 3-epi-DON is substantially less toxic than DON.
Keywords:Deoxynivalenol  Vomitoxin  DON  Cytotoxicity  BrdU bioassay  3T3 fibroblasts cell line  MTT bioassay  Caco-2 cell line  3ADON"}  {"#name":"keyword"  "$":{"id":"kwrd0065"}  "$$":[{"#name":"text"  "_":"3-acetyl-deoxynivalenol  15ADON"}  {"#name":"keyword"  "$":{"id":"kwrd0085"}  "$$":[{"#name":"text"  "_":"15-acetyl-deoxynivalenol  ATCC"}  {"#name":"keyword"  "$":{"id":"kwrd0095"}  "$$":[{"#name":"text"  "_":"American Type Culture Collection  BA"}  {"#name":"keyword"  "$":{"id":"kwrd0105"}  "$$":[{"#name":"text"  "_":"basophils  BrdU"}  {"#name":"keyword"  "$":{"id":"kwrd0115"}  "$$":[{"#name":"text"  "_":"5-bromo-2′-deoxyuridine  DMEM"}  {"#name":"keyword"  "$":{"id":"kwrd0125"}  "$$":[{"#name":"text"  "_":"Dulbecco's modified Eagle's medium  DMSO"}  {"#name":"keyword"  "$":{"id":"kwrd0135"}  "$$":[{"#name":"text"  "_":"dimethyl sulfoxide  DOM-1"}  {"#name":"keyword"  "$":{"id":"kwrd0145"}  "$$":[{"#name":"text"  "_":"deepoxy-deoxynivalenol  DON"}  {"#name":"keyword"  "$":{"id":"kwrd0155"}  "$$":[{"#name":"text"  "_":"deoxynivalenol  EDTA"}  {"#name":"keyword"  "$":{"id":"kwrd0165"}  "$$":[{"#name":"text"  "_":"ethylenediamine tetraacetic acid  ELISA"}  {"#name":"keyword"  "$":{"id":"kwrd0175"}  "$$":[{"#name":"text"  "_":"enzyme-linked immunosorbent assay  EO"}  {"#name":"keyword"  "$":{"id":"kwrd0185"}  "$$":[{"#name":"text"  "_":"eosinophils  HCT"}  {"#name":"keyword"  "$":{"id":"kwrd0195"}  "$$":[{"#name":"text"  "_":"hematocrit  HGB"}  {"#name":"keyword"  "$":{"id":"kwrd0205"}  "$$":[{"#name":"text"  "_":"hemoglobin  HSCCC"}  {"#name":"keyword"  "$":{"id":"kwrd0215"}  "$$":[{"#name":"text"  "_":"high-speed counter-current chromatography  IgA"}  {"#name":"keyword"  "$":{"id":"kwrd0225"}  "$$":[{"#name":"text"  "_":"immunoglobulin A  IgG"}  {"#name":"keyword"  "$":{"id":"kwrd0235"}  "$$":[{"#name":"text"  "_":"immunoglobulin G  IgM"}  {"#name":"keyword"  "$":{"id":"kwrd0245"}  "$$":[{"#name":"text"  "_":"immunoglobulin M  Lethal concentration 50  LY"}  {"#name":"keyword"  "$":{"id":"kwrd0265"}  "$$":[{"#name":"text"  "_":"lymphocytes  MAPKs"}  {"#name":"keyword"  "$":{"id":"kwrd0275"}  "$$":[{"#name":"text"  "_":"mitogen-activated protein kinases  MCH"}  {"#name":"keyword"  "$":{"id":"kwrd0285"}  "$$":[{"#name":"text"  "_":"mean cell hemoglobin  MCHC"}  {"#name":"keyword"  "$":{"id":"kwrd0295"}  "$$":[{"#name":"text"  "_":"mean cell hemoglobin concentration  MCV"}  {"#name":"keyword"  "$":{"id":"kwrd0305"}  "$$":[{"#name":"text"  "_":"mean cell volume  MO"}  {"#name":"keyword"  "$":{"id":"kwrd0315"}  "$$":[{"#name":"text"  "_":"monocytes  MPV"}  {"#name":"keyword"  "$":{"id":"kwrd0325"}  "$$":[{"#name":"text"  "_":"mean platelet volume  MTT"}  {"#name":"keyword"  "$":{"id":"kwrd0335"}  "$$":[{"#name":"text"  "_":"3-(4  5-dimethylthiazol-2-yl)-2  5-diphenyltetrazolium bromide  MW"}  {"#name":"keyword"  "$":{"id":"kwrd0345"}  "$$":[{"#name":"text"  "_":"molecular weight  NE"}  {"#name":"keyword"  "$":{"id":"kwrd0355"}  "$$":[{"#name":"text"  "_":"neutrophils  NIV"}  {"#name":"keyword"  "$":{"id":"kwrd0365"}  "$$":[{"#name":"text"  "_":"nivalenol  PBS"}  {"#name":"keyword"  "$":{"id":"kwrd0375"}  "$$":[{"#name":"text"  "_":"phosphate buffered saline  PLT"}  {"#name":"keyword"  "$":{"id":"kwrd0385"}  "$$":[{"#name":"text"  "_":"platelets  RBC"}  {"#name":"keyword"  "$":{"id":"kwrd0395"}  "$$":[{"#name":"text"  "_":"red blood cells  RDW"}  {"#name":"keyword"  "$":{"id":"kwrd0405"}  "$$":[{"#name":"text"  "_":"red cell distribution width  WBC"}  {"#name":"keyword"  "$":{"id":"kwrd0415"}  "$$":[{"#name":"text"  "_":"white blood cells
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