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Increased cytotoxicity of food-borne mycotoxins toward human cell lines in vitro via enhanced cytochrome p450 expression using the MTT bioassay

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Abstract

Eight food-borne mycotoxins epidemiologically implicated in human disease were tested for their cytotoxic effects on human cells previously immortalised and transfected to introduce human cytochrome p450(CYP 450) genes. Such cells retain many characteristics of normal cell growth and differentiation while simultaneously having the potential of either increasing or decreasing the metabolic activity (cytotoxicity) of the challenging mycotoxins. The MTT assay provided an indication of cytotoxicity. Of the nine CYP 450s introduced CYP1A2 was most effective,rendering the cells 540 times more sensitive than the control cells to aflatoxin B1, 28 times more sensitive to aflatoxin G1 and 8-fold more sensitive to ochratoxin A. CYP3A4 resulted in the cells being 211 times more toxic to aflatoxin B1 and 8-fold more toxic to aflatoxin G1 while CYP 2A6, CYP 3A5 and CYP 2E1 also produced observable effects. No increase in metabolic activity was found using cyclopiazonic acid, deoxynivalenol,fumonisin B1, patulin or T-2 toxin. CD5Os were calculated for the mycotoxins against the non-CYP-introduced control cells. There was almost a five order of magnitude difference between the most toxic,T-2 toxin (CD50 0.0057 μg/ml) and the least toxic, fumonisin 1(CD50 476.2 μg/ml). In vitro biological assays thus provide an excellent system for quantifying the often low CD50s expressed bymycotoxins in foods.

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Authors and Affiliations

  1. Department of Bioscience and Biotechnology, University of Strathclyde, 204 George Street, Glasgow, G1 1XW, UK

    C.W. Lewis, J.E. Smith & J.G. Anderson

  2. RC Department of Medical Oncology, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK

    R.I. Freshney

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  1. C.W. Lewis
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  2. J.E. Smith
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  3. J.G. Anderson
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  4. R.I. Freshney
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Lewis, C., Smith, J., Anderson, J. et al. Increased cytotoxicity of food-borne mycotoxins toward human cell lines in vitro via enhanced cytochrome p450 expression using the MTT bioassay. Mycopathologia 148, 97–102 (2000). https://doi.org/10.1023/A:1007130923558

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