Discrepant dose responses of bisphenol A on oxidative stress and DNA methylation in grass carp ovary cells

Abstract

Bisphenol A (BPA), is a common contaminant in diverse environmental compartments and its endocrine disruptive effect on living organisms has been widely reported. Further works are still required to facilitate the research on cytotoxicity and genotoxicity. In the present study, grass carp ovary (GCO) cells were used to investigate cellular oxidative stress and genomic DNA methylation under BPA exposure. Results showed that BPA exposure for 48 h arrested cell proliferation and viability. The oxidative stress was distinctly enhanced with increased reactive oxygen species (ROS), malondialdehyde level, and oxidation of reduced glutathione (GSH) in 30 μM BPA group. Furthermore, the global 5-methylcytosine (5 mC) level was elevated and showed inverted U-shaped responses to the BPA doses. Besides, one-carbon metabolism and de novo GSH synthesis were disrupted at 30 μM BPA. Current data suggested that low dose of BPA exposure could exhibit hormesis in recycling circular biosynthesis of GSH and scavenging ROS to create a relatively reductive intracellular environment, and up-regulate transcripts of methyltransferases that increased the 5 mC level in GCO cells. While high dose of BPA distinctly induced oxidative stress, elevated de novo GSH synthesis, and then attenuated transmethylation activity and decreased 5 mC level. Current study highlighted the discrepant dose responses of BPA in fish ovary cells that facilitated the understanding of pleiotropic consequences in organisms.