Bisphenol-A reduces DNA methylation after metabolic activation

Area of Science:

• Epigenetics
• Environmental Toxicology
• Molecular Biology

Background:

• Bisphenol-A (BPA) is an environmental contaminant linked to adverse health effects potentially mediated by epigenetic changes.
• Transgenic yeast expressing human DNA methyltransferase (DNMT yeast) provide a model for epigenotoxicology studies.

Purpose of the Study:

• To investigate the effects of BPA and its metabolites on gene transcription and DNA methylation.
• To evaluate a novel in vitro method for screening chemicals that alter the epigenome via metabolic activation.

Main Methods:

• Utilized transgenic yeast (DNMT yeast) with a FLO1 promoter-driven green fluorescence reporter protein (GFP) to assess BPA's impact.
• Investigated effects with and without metabolic activation (S-9 mix).
• Analyzed FLO1 gene mRNA expression, flocculation, and global DNA methylation in HEK293 cells.

Main Results:

• BPA, with metabolic activation, inhibited GFP expression and FLO1 mRNA levels.
• A BPA metabolite, MBP, also demonstrated inhibitory effects on DNA methylation.
• MBP showed no significant inhibition on a modified reporter gene with reduced CpG motifs, suggesting a methylation-dependent mechanism.

Conclusions:

• BPA metabolites can inhibit DNA methylation.
• The study presents a novel in vitro approach for identifying epigenome-altering chemicals dependent on metabolic activation.