Investigation of the effects of fumonisin B1 on genes playing role in cancer-related pathways in cell cultures

Fumonisin B1 (FB1), which is emerged by contamination of corn and similar products with Fusarium species, causes a high risk for human and animal health. In the studies, it has been reported that FB1 shows hepatotoxic, nephrotoxic, neurotoxic, immunotoxic and teratogenic effects. In addition, FB1 is known to play a role in cancer development. The reason of this effect is the accumulation of sphinganine, which plays an important role in the cell proliferation pathway and apoptic modulation, and the impairment in sphingolipid biosynthesis. In addition, it is suggested that FB1 is not genotoxic and can act through epigenetic mechanisms in the carcinogenesis process. In the thesis study, it has been aimed to investigate the role of DNA methylation, one of the epigenetic mechanisms, in the toxicity og FB1. So that, global DNA methylation of FB1, DNA methylation of tumor suppressor genes and expression of altered genes in human kidney cells (HK-2) has been investigated. When the cytotoxicity of FB1 was examined, for 24 h with 200 μM concentration, the death rates were observed 34% in MTT test and 38% in NRU test. Therefore, it could not be reached to an inhibition concentration rate of 50%. IC50 could not be calculated. It was observed that FB1 exposure at 100 μM concentration increased global DNA methylation by 2,23 fold, but this was not related to changes in DNMT enzymes. The effect of 24 hour FB1 exposure at 10, 50 and 100 μM concentrations on methylation in tumor suppressor genes were investigated by studying panel arrays. Significant increases in methylation levels at 50 and 100 μM concentrations have been observed in mosf of the genes. These results have been shown to be consistent with the expression results during the study. Significant decreases in the expression of selected genes CD44, CDKN1A, CDKN2B, CTNNB1, MYC and p16. It has been expected that the thesis study will contribute to the studies on the mechanisms that play a role in FB1 cancer pathways.