The effects of different bisphenol derivatives on oxidative stress, DNA damage and DNA repair in RWPE-1 cells: A comparative study

J Appl Toxicol. 2020 May;40(5):643-654. doi: 10.1002/jat.3934. Epub 2019 Dec 26.

Abstract

Bisphenol A (BPA) is a well-known endocrine disruptor and it is widely used mainly in the plastics industry. Due to recent reports on its possible impact on health (particularly on the male reproductive system), bisphenol F (BPF) and bisphenol S (BPS) are now being used as alternatives. In this study, RWPE-1 cells were used as a model to compare cytotoxicity, oxidative stress-causing potential and genotoxicity of these chemicals. In addition, the effects of the bisphenol derivatives were assessed on DNA repair proteins. RWPE-1 cells were incubated with BPA, BPF, and BPS at concentrations of 0-600 μM for 24 h. The inhibitory concentration 20 (IC20 , concentration that causes 20% of cell viability loss) values for BPA, BPF, and BPS were 45, 65, and 108 μM, respectively. These results indicated that cytotoxicity potentials were ranked as BPA > BPF > BPS. We also found alterations in superoxide dismutase, glutathione peroxidase and glutathione reductase activities, and glutathione and total antioxidant capacity in all bisphenol-exposed groups. In the standard and modified Comet assay, BPS produced significantly higher levels of DNA damage vs the control. DNA repair proteins (OGG1, Ape-1, and MyH) involved in the base excision repair pathway, as well as p53 protein levels were down-regulated in all of the bisphenol-exposed groups. We found that the BPA alternatives were also cytotoxic and genotoxic, and changed the expressions of DNA repair enzymes. Therefore, further studies are needed to assess whether they can be used safely as alternatives to BPA or not.

Keywords: Bisphenol A; DNA repair ezymes; bisphenol F; bisphenol S; cytotoxicity; oxidative stress.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / metabolism
  • Benzhydryl Compounds / toxicity*
  • Cell Line
  • Comet Assay
  • DNA Damage*
  • DNA Repair / drug effects*
  • Endocrine Disruptors / toxicity*
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Gene Expression Regulation
  • Humans
  • Male
  • Oxidative Stress / drug effects*
  • Phenols / toxicity*
  • Prostate / drug effects*
  • Prostate / metabolism
  • Prostate / pathology
  • Risk Assessment
  • Sulfones / toxicity*

Substances

  • Antioxidants
  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Phenols
  • Sulfones
  • bisphenol F
  • bis(4-hydroxyphenyl)sulfone
  • bisphenol A