Effects of BPA on global DNA methylation and global histone 3 lysine modifications in SH-SY5Y cells: An epigenetic mechanism linking the regulation of chromatin modifiying genes.

Bisphenol A (BPA), an estrogenic endocrine disruptor, is widely used in the production of polycarbonate plastic and epoxy resins, resulting in high risk on human health. In present study we aimed to investigate the effects of BPA on global and gene specific DNA methylation, global histone modifications and regulation of chromatin modifiying enzymes in human neuroblastoma cells (SH-SY5Y). Cells were treated with BPA at 0.1, 1 and 10µM concentrations for 48 and 96h. IC50 value of BPA was determined as 183 and 129µM in SH-SY5Y cells after 24h by MTT and NRU tests, respectively. We observed significant alterations on the 5-mC% levels (1.3 fold) and 5-hmC% levels (1.67 fold) after 10µM of BPA for 96h. Significant decrease was identified in H3K9me3 and H3K9ac after 10µM of BPA for 96h while decrease was observed in H3K4me3 at 10µM of BPA for 48h. Alterations were observed in chromatin modifiying genes including G9a, EZH2, SETD8, SETD1A, HAT1, SIRT1, DNMT1, RIZ1 and Suv39h1 after 96h of BPA exposure. Taken together, this study suggests that BPA might modulate the epigenetic regulators which would be key molecular events in the toxicity of endocrine disrupting chemicals.

Total sialic acid profile in regressing and remodelling organs during the metamorphosis of marsh frog (Pelophylax ridibundus Pallas 1771).

This study aimed to investigate the functional relationship of sialic acid in regressing and remodelling organs such as the tail, small intestine and liver during the metamorphosis of Pelophylax ridibundus. For this purpose, four groups were composed according to developmental periods by considering Gosner's criteria (1964). Our findings showed that the sialic acid content of the larval tail has an opposite profile to cell death process. Although the sialic acid content of the small intestine and liver did not change evidently during metamorphosis, it increased after the completion of metamorphosis. Frog tail extensively exhibited cell death process and decreased proliferative activity and underwent complete degeneration during metamorphic climax. In spite of increased apoptotic index, a decreased sialic acid level in the tail tissues during climax can be the indication of a death cell removal process. However, the intestine and the liver included both cell death and proliferative process and remodelling in their adult forms. Thus, their sialic acid profiles during metamorphosis were different from the tail's profile. These data show that sialic acid may be an indicator of the presence of some cellular events during metamorphosis and that it can have different roles in the developmental process depending on the organ's fate throughout metamorphosis.