Evaluation of the cytotoxic and genotoxic effects of mycotoxin fusaric acid

Abstract

Fusaric acid (FA) is produced by several Fusarium species and is commonly found in grains. This investigation was performed to evaluate the cytotoxic and genotoxic effects of FA either in human cervix carcinoma (HeLa) cell line using 3-(4,5-dimethylthiazolyl-2)-2,5 diphenyltetrazolium bromide (MTT) assay and in human lymphocytes using chromosome aberrations (CAs), sister chromatid exchanges (SCEs), micronuclei (MN) as well as comet assay in vitro. The cells were treated with 0.78, 1.56, 3.125, 6.25, 12.50, 25, 50, 100, 200, and 400 µg/mL concentrations of FA. It has potent cytotoxic effect on HeLa cell line measured by MTT assay especially at higher concentrations (200, 400 µg/mL). The half of inhibitory concentration (IC) evidenced by FA in the HeLa cells was 200 μg/mL at 24 h and between 200 and 400 μg/mL at 48 h. It was also observed that FA produced a significant decrease in mitotic index (MI) at 12.50 µg/mL compared to solvent control. Furthermore, it indicated a cytotoxic effect at the concentrations ranging from 25 to 400 μg/mL in human lymphocytes. The results of this research point out that being exposed to FA at high concentrations show cytotoxicity. Besides FA induced comet tail intensity at 3.125, 6.25, and 12.50 µg/mL concentrations in isolated human lymphocytes. On the other hand, no genotoxic effects were seen in human lymphocytes in vitro using CA, SCE and MN assays.

The Role of Nitrogen Fertilization on the Occurrence of Regulated, Modified and Emerging Mycotoxins and Fungal Metabolites in Maize Kernels

“…Moreover, a recent review [ 26 ] underlined an interactive toxicity of MON and FB 1 . FA [ 27 , 28 ], BEA [ 29 , 30 ] and FUS [ 31 , 32 ] also showed toxic effects in humans and animals. Instead, there is a lack of toxicological data for BIK, and further studies are needed [ 33 ].…”

Fusaric acid-induced promoter methylation of DNA methyltransferases triggers DNA hypomethylation in human hepatocellular carcinoma (HepG2) cells

“…In contrary, other Fusarium produced mycotoxins such as deoxynivalenol and T2 toxin induce global DNA hypermethylation and histone demethylation [60,61]. The toxicity of FA has been mainly attributed to oxidative stress, DNA damage, and apoptosis [10,[12][13][14][15]62], and the FA-induced global DNA hypomethylation may provide an alternative mechanism by which FA induces its genotoxic and cytotoxic effects.…”

Evaluation of In Vitro and In Vivo Anticancer Activities of Mycotoxins

“…77 Mamur ve ark.nın yaptığı çalışmada, insan serviks karsinomuna (HeLa) karşı hücre canlılığını önemli ölçüde azaltmıştır. 78 Ghazi ve ark.nın yapmış oldukları bir çalışmada, FA'nın tümör baskılayıcı gen olarak bilinen p53 gen ekspresyonu üzerindeki etkileri değerlendirilmiştir. Hepatoselüler karsinom hücre hattı (HepG2) 0, 25, 50, 104 ve 150 µg/mL dozlarında FA uygulamasını takiben 24 saat içerisinde DNA, RNA ve protein izolasyonları yapılarak p53 gen ekspresyonu incelenmiştir.…”