Fumonisin FB1 treatment acts synergistically with methyl donor deficiency during rat pregnancy to produce alterations of H3‐ and H4‐histone methylation patterns in fetuses

Abstract

Scope Prenatal folate and methyl donor malnutrition lead to epigenetic alterations that could enhance susceptibility to disease. Methyl‐deficient diet (MDD) and fumonisin FB1 are risk factors for neural tube defects and cancers. Evidence indicates that FB1 impairs folate metabolism. Methods and results Folate receptors and four heterochromatin markers were investigated in rat fetuses liver derived from dams exposed to MDD and/or FB1 administered at a dose twice higher than the provisional maximum tolerable daily intake (PMTDI = 2 μg/kg/day). Even though folate receptors transcription seemed up‐regulated by methyl depletion regardless of FB1 treatment, combined MDD/FB1 exposure might reverse this up‐regulation since folate receptors transcripts were lower in the MDD/FB1 versus MDD group. Methyl depletion decreased H4K20me3. Combined MDD/FB1 decreased H4K20me3 even more and increased H3K9me3. The elevated H3K9me3 can be viewed as a defense mechanism inciting the cell to resist heterochromatin disorganization. H3R2me2 and H4K16Ac varied according to this mechanism even though statistical significance was not consistent. Conclusion Considering that humans are exposed to FB1 levels above the PMTDI, this study is relevant because it suggests that low doses of FB1 interact with MDD thus contributing to disrupt the epigenetic landscape.

Role of fumonisin B1 on DNA methylation changes in rat kidney and liver cells

“…This is the first study that investigates the gene-specific DNA methylation in the toxicity mechanisms of FB1 for the risk assessment process. In a recent study on the epigenetic mechanisms in FB1 toxicity, FB1 can alter histone modifications which lead to heterochromation disorganization at low doses (Pellanda et al, 2012). In this work, it was shown that H4K20me3 significantly decreased, while H3K9me3 significantly increased in the fetuses when pregnant dams were exposed to methyl-deficient diet and FB1 (Pellenda et al, 2012).…”

Fumonisin B1 Epigenetically Regulates PTEN Expression and Modulates DNA Damage Checkpoint Regulation in HepG2 Liver Cells

“…FB 1 can also induce epigenetic changes through the post-translational modifications of histones, but no study to date has investigated these changes in humans [ 63 , 64 , 65 ]. Here, we identified changes to H3K4 methylation.…”

Biochemical mutagens affect the preservation of fungi and biodiversity estimations

“…For example, the mechanisms of fumonisin carcinogenicity do not appear to involve interaction with DNA and the carcinogenic activity of fumonisins may be mediated via epigenetic mechanisms (Coulombe 1993). Fumonisin B1 induced hypermethylation of DNA (Mobio et al 2000) and may be involved in histone modifications (Pellanda et al 2012). Ochratoxin A also has epigenetic effects (Marin-Kuan et al 2008) and is likely to act through a network of interacting epigenetic mechanisms, including protein synthesis inhibition, oxidative stress, and the activation of specific cell signaling pathways, which are responsible for carcinogenicity.…”