title: Sequential dietary exposure to aflatoxin B1 and fumonisin B1 in F344 rats increases liver preneoplastic changes indicative of a synergistic interaction.
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.
authors.affiliation: Department of Environmental Health Science, University of Georgia, Athens, GA, USA.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Qian
authors.affiliation: Department of Environmental Health Science, University of Georgia, Athens, GA, USA.
authors.forename: Lili
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Environmental Health Science, University of Georgia, Athens, GA, USA.
authors.forename: Shuhan
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Environmental Health Science, University of Georgia, Athens, GA, USA.
authors.forename: Kathy S
authors.initials: KS
authors.lastname: Xue
authors.affiliation: Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, USA.
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: Mitchell
authors.affiliation: Department of Environmental Health Science, University of Georgia, Athens, GA, USA.
authors.forename: Jianjia
authors.initials: J
authors.lastname: Su
authors.affiliation: Institute of Biomedical and Microbial Biotechnology, Cape Peninsula University of Technology, PO Box 1906, Bellville, 7535, South Africa.
authors.forename: Wentzel C
authors.initials: WC
authors.lastname: Gelderblom
authors.affiliation: Department of Environmental Health Science, University of Georgia, Athens, GA, USA; USDA-ARS, Toxicology and Mycotoxin Research Unit, R.B. Russell Research Center, National Poultry Disease Research Center, Athens, GA, USA.
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Riley
authors.affiliation: Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, USA.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Phillips
authors.affiliation: Department of Environmental Health Science, University of Georgia, Athens, GA, USA. Electronic address: jswang@uga.edu.
authors.forename: Jia-Sheng
authors.initials: JS
authors.lastname: Wang
mesh_terms: D016604:Aflatoxin B1 / Q000633:toxicity*; D000818:Animals; D002274:Carcinogens, Environmental / Q000633:toxicity; D004032:Diet / Q000009:adverse effects*; D004347:Drug Interactions; D004357:Drug Synergism; D037341:Fumonisins / Q000633:toxicity*; D051549:Glutathione S-Transferase pi / Q000378:metabolism; D007150:Immunohistochemistry; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D011042:Poisons / Q000633:toxicity; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D002274:Carcinogens, Environmental; D037341:Fumonisins; D011042:Poisons; C056933:fumonisin B1; D016604:Aflatoxin B1; D051549:Glutathione S-Transferase pi; C496558:Gstp1 protein, rat
keywords: Aflatoxin B1; Animal model; Carcinogenesis; Fumonsin B1; Liver GST-P positive foci