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Open AccessArticle

Reduced Toxicity of Trichothecenes, Isotrichodermol, and Deoxynivalenol, by Transgenic Expression of the Tri101 3-O-Acetyltransferase Gene in Cultured Mammalian FM3A Cells

1
Graduate School of Science and Engineering, Toyo University, 2100 Kujirai, Kawagoe, Saitama 350-8585, Japan
2
Graduate School of Engineering, Toyo University, 2100 Kujirai, Kawagoe, Saitama 350-8585, Japan
3
Department of Biological Mechanisms and Functions, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan
4
Research Institute of Industrial Technology, Toyo University, 2100 Kujirai, Kawagoe, Saitama 350-8585, Japan
*
Author to whom correspondence should be addressed.
Toxins 2019, 11(11), 654; https://doi.org/10.3390/toxins11110654
Received: 14 September 2019 / Revised: 30 October 2019 / Accepted: 7 November 2019 / Published: 10 November 2019
(This article belongs to the Special Issue Toxicological Effects of Mycotoxin on Target Cells)
In trichothecene-producing fusaria, isotrichodermol (ITDol) is the first intermediate with a trichothecene skeleton. In the biosynthetic pathway of trichothecene, a 3-O-acetyltransferase, encoded by Tri101, acetylates ITDol to a less-toxic intermediate, isotrichodermin (ITD). Although trichothecene resistance has been conferred to microbes and plants transformed with Tri101, there are no reports of resistance in cultured mammalian cells. In this study, we found that a 3-O-acetyl group of trichothecenes is liable to hydrolysis by esterases in fetal bovine serum and FM3A cells. We transfected the cells with Tri101 under the control of the MMTV-LTR promoter and obtained a cell line G3 with the highest level of C-3 acetylase activity. While the wild-type FM3A cells hardly grew in the medium containing 0.40 μM ITDol, many G3 cells survived at this concentration. The IC50 values of ITDol and ITD in G3 cells were 1.0 and 9.6 μM, respectively, which were higher than the values of 0.23 and 3.0 μM in the wild-type FM3A cells. A similar, but more modest, tendency was observed in deoxynivalenol and 3-acetyldeoxynivalenol. Our findings indicate that the expression of Tri101 conferred trichothecene resistance in cultured mammalian cells. View Full-Text
Keywords: trichothecene; biosynthetic pathway; acetyltransferase; deacetylase; deoxynivalenol; 3-acetyldeoxynivalenol; isotrichodermol; isotrichodermin trichothecene; biosynthetic pathway; acetyltransferase; deacetylase; deoxynivalenol; 3-acetyldeoxynivalenol; isotrichodermol; isotrichodermin
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Tanaka, N.; Takushima, R.; Tanaka, A.; Okada, A.; Matsui, K.; Maeda, K.; Aikawa, S.; Kimura, M.; Takahashi-Ando, N. Reduced Toxicity of Trichothecenes, Isotrichodermol, and Deoxynivalenol, by Transgenic Expression of the Tri101 3-O-Acetyltransferase Gene in Cultured Mammalian FM3A Cells. Toxins 2019, 11, 654.

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