Background. Nonsteroid estrogen – bisphenol A (BPA) can have a detrimental effect on human health, and therefore poses a potential threat to humans. The critical window for the effect of BPA is the time of early development of the embryo, especially during the activation of the embryonic genome during development to the stage of blastocyst. Therefore, it is especially important to understand how DNA methylation is modified in embryos of the earliest developmental period under the influence of BPA.
Materials and methods. Mice hybrids F1 (CBAXC57BL) were once administered 0, 8 mg of BPA per mouse and the level of DNA methylation was estimated by detection the fluorescence of antibodies against 5-MeC in nuclei of GD3 and GD9 embryos. In other series, the level of DNA methylation and the rate of blastocyst development were estimated following cultivation of one- and two cells embryos in the presence of BPA (50 or 100 µM) during 72-96 hours in vitro.
Results. BPA exposure induced the decrease of the level of DNA methylation in GD3embryos received toxicant in utero, the amount of blastomeres in these embryos was decreased too. The level of DNA methylation in GD9 embryos was slightly higher than in control group. Upon cultivation of one-two cells embryos, BPA decreased the level of DNA methylation and the rate of embryos development to blastocyst stage.
Conclusion. We have determined that early embryogenesis is highly sensitive period to the BPA effects. Such effect is most likely due to active reprogramming processes in this period, primarily related to DNA demethylation/methylation de novo of both the whole genome and individual genes.
BACKGROUND: Neuroblastoma is one of the most common extracranial solid tumors in childhood. At present, epigenetic disorders play a significant role in neoplasms development. Since epigenetic changes in the cell are quite dynamic and reversible, epigenome-modulating exogenous agents can be used in epigenetic targeted therapy for various types of tumors. Therefore, the identification of these agents is still significant. Lactoferrin is one such potential molecule from the transferrin family. Currently, the anti-tumor properties of lactoferrin have been identified, but its effect on the epigenome of cells of various tumors types, particularly on neuroblastomas, is practically unknown.
AIM: To study the effect of the exogenous recombinant human apolactoferrin on the viability and epigenomic status of IMR-32 neuroblastoma cells.
MATERIALS AND METHODS: We studied human IMR-32 neuroblastoma cells after 72 hours of exposure to 8 doses of recombinant human apolactoferrin: 0.1, 0.5, 1, 5, 10, 50, 100 and 500 g/ml. The level of genome-wide DNA methylation and the degree of chromatin compaction in IMR-32 cells were quantified using commercial kits 5-mC DNA ELISA Kit, Global DNA Methylation LINE-1 Kit, as well as enzymatic hydrolysis of MspI / HpaII and DNaseI.
RESULTS: The recombinant apolactoferrin reduces the viability of IMR-32 and, depending on the dose, differentially affects the level of genome-wide DNA methylation (СpG dinucleotides, CCGG sites, LINE-1 repeats) and the degree of chromatin compaction. At the same time, a complex picture of the epigenomic cellular response to the effect of apo-lactoferrin was observed (nonlinear nonmonotonic dose-effect relationship).
CONCLUSIONS: We assumed that apolactoferrin modulates gene activity through epigenetic mechanisms, in particular, by changing the DNA methylation pattern and affecting the chromatin structure, which may be one of the molecular mechanisms of its anti-tumor effect.
The review describes the molecular mechanisms and biological effects of bisphenol A exposure, which is a chemical (ecotoxicant) that destroys the endocrine system and has epigenetic toxicity.
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