Sequential dietary exposure to aflatoxin B1 and fumonisin B1 in F344 rats increases liver preneoplastic changes indicative of a synergistic interaction |
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| Affiliation: | 1. Department of Environmental Health Science, University of Georgia, Athens, GA, USA;2. Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, USA;3. Institute of Biomedical and Microbial Biotechnology, Cape Peninsula University of Technology, PO Box 1906, Bellville, 7535, South Africa;4. USDA-ARS, Toxicology and Mycotoxin Research Unit, R.B. Russell Research Center, National Poultry Disease Research Center, Athens, GA, USA;1. Procter & Gamble, Mason Business Center, 8700 Mason - Montgomery Rd, Mason, OH, 45040, USA;2. Procter & Gamble Technical Centre, Whitehall Lane, Egham, Surrey, TW20 9AW, UK;1. Biomedical Research and Innovation Platform, South African Medical Research Council, PO Box 19070, Tygerberg 7505, South Africa;2. Mycotoxicology and Chemoprevention Research Group, Institute of Biomedical and Microbial Biotechnology, Cape Peninsula University of Technology, PO Box 1906, Bellville 7535, South Africa;3. Oxidative Stress Research Centre, Institute of Biomedical and Microbial Biotechnology, Cape Peninsula University of Technology, PO Box 1906, Bellville 7535, South Africa;4. Biostatistics Unit, South African Medical Research Council, PO Box 19070, Tygerberg, South Africa;5. Department of Biochemistry, University of Stellenbosch, Private Bag X1, Matieland 7602, South Africa;1. Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, 100083, Beijing, China;2. Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, 100083, Beijing, China;3. The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, 100083, Beijing, China;1. Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China;2. Department of Animal Science, Cornell University, Ithaca, NY 14853, USA |
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| Abstract: | Dietary co-exposure to aflatoxin B1 (AFB1) and fumonisin B1 (FB1) and their interaction on hepatocellular carcinogenesis is of particular concern in toxicology and public health. In this study we evaluated the liver preneoplastic effects of single and sequential dietary exposure to AFB1 and FB1 in the F344 rat carcinogenesis model. Serum biochemical alterations, liver histopathological changes, and the formation of liver glutathione S transferase positive (GST-P+) foci were the major outcome parameters examined. Compared to the AFB1-only treatment, the FB1-only treatment induced less dysplasia, and more apoptosis and mitoses. Sequential AFB1 and FB1 treatment lead to increased numbers of dysplasia, apoptosis and foci of altered hepatocytes, as compared to either mycotoxin treatment alone. More importantly, sequential exposure to AFB1 and FB1 synergistically increased the numbers of liver GTP-P+ foci by approximately 7.3-and 12.9-fold and increased the mean sizes of GST-P+ foci by 6- and 7.5-fold, respectively, as compared to AFB1- or FB1-only treatment groups. In addition, liver ALT and AST levels were significantly increased after sequential treatment as compared to single treatment groups. The results demonstrate the interactive effect of dietary AFB1 and FB1 in inducing liver GST-P+ foci formation and provide information to model future intervention studies. |
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| Keywords: | Aflatoxin B1 Fumonsin B1 Liver GST-P positive foci Carcinogenesis Animal model |
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