Global DNA Hypomethylation and and Promoter Hypermethylation in Rat Kidney Cells after Bisphenol A Exposure.

OBJECTIVES

Bisphenol A (BPA) is a synthetic monomer used in the production of polycarbonate and an environmental contaminant with endocrine disrupting properties. BPA release from plastic carriers is thought to cause high amounts of exposure, which result in high risk to human and environment health.

MATERIALS AND METHODS

The study examined the possible changes in global DNA methylation, CpG promoter DNA methylation, and gene expressions of and after BPA exposure in rat kidney epithelial cells (NRK-52E).

RESULTS

The IC values of BPA in NRK-52E cells were 133.42 and 101.74 μM in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red uptake tests, respectively. The cells were treated with BPA at 1 nM, 10 nM, 100 nM, 1 μM, and 10 μM concentrations for 24 h and at 100 nM concentration for 24, 48, 72, 96 h, and 6 days. Decreased global 5-methylcytosine levels were observed after 48, 72, 96 h, and 6 days at the concentration of 100 nM BPA. Changes in CpG promoter DNA methylation were detected in the genes of and in BPA-treated NRK-52E cells. Expression levels of and changed in response to BPA at the high concentrations after 24 h treatment, whereas 100 nM exposure to BPA altered gene expression after 48, 72, and 96 h.

CONCLUSION

These results indicate that changes in global and gene-specific DNA methylation may play an important role in the mechanism of BPA toxicity in kidney cells.