Effects of aflatoxin and fumonisin on gene expression of growth factors and inflammation-related genes in a human hepatocyte cell line

Author:

Wu Hang12ORCID,Xu Ya3,Gong Yun Yun2,Huntriss John1,Routledge Michael N45

Affiliation:

1. School of Medicine, University of Leeds , Leeds LS2 9JT , United Kingdom

2. School of Food Science and Nutrition, University of Leeds , Leeds LS2 9JT , United Kingdom

3. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun-Yat University , Guangzhou 51006 , China

4. Leicester Medical School, George Davies Centre , Lancaster Rd, Leicester LE1 7HA , United Kingdom

5. School of Food and Biological Engineering, Jiangsu University , Zhenjiang 212013 , China

Abstract

Abstract Aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are mycotoxins widely distributed in maize and maized-based products, often occurring together. The implications of co-exposure to aflatoxin and fumonsin for human health are numerous, but a particular concern is the potential of FB1 to modulate AFB1 hepatotoxicity. This study evaluated the toxicity of these mycotoxins, alone or combined, in a human non-tumorigenic liver cell line, HHL-16 cells, and assessed the effects of AFB1 and FB1 on expression of genes involved in immune and growth factor pathways. The results demonstrated that in HHL-16 cells, both AFB1 and FB1 had dose-dependent and time-dependent toxicity, and the combination of them showed a synergistic toxicity in the cells. Moreover, AFB1 caused upregulation of IL6, CCL20, and BMP2, and downregulation of NDP. In combination of AFB1 with FB1, gene expression levels of IL6 and BMP2 were significantly higher compared to individual FB1 treatment, and had a tendency to be higher than individual AFB1 treatment. This study shows that FB1 may increase the hepatoxicity of AFB1 through increasing the inflammatory response and disrupting cell growth pathways.

Funder

China Scholarship Council

University of Leeds

United Kingdom Environmental Mutagen Society Small Grants Scheme

Publisher

Oxford University Press (OUP)

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